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      • id669
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      • abstract_of_study<p>\n Safe and Effective Contraception is a universal right for all men and women. Many women of reproductive age are unable to  use the current contraception methods available to them and rely on their male partners to protect them from unplanned pregnancy.  A majority of men surveyed internationally reported interest and willingness to use contraceptive methods; unfortunately no safe, highly effective reversible method is available to men interested in sharing the responsibility of family planning.The primary objective  of the CCN017 male contraception study is to determine the contraception efficacy, safety and acceptablily for a couple provided by daily application of the male partner of a gel containing Nesteron 8mg and Testesterone 62mg (NES 8/T 62) for a period of 52 weeks</p>\n<p>\n <strong>Methodology</strong></p>\n<p>\n This is a prospective, phase IIb, open label, single arm, multicenter study. The study consists of a screening phase lasting 4 to 8 weeks, a suppression phase estimated to last up to 20 weeks, a 52- week maintenance/efficacy phase, and a 24-week (estimated) recovery phase.  The study population will comprise healthy men ages 18 – 50 years, involved in a stable, monogamous, relationship  with an 18 – 34 year-old female partner (at the time of enrolment) with regular cycles per patient report from her previous non-hormonal contraceptive gynecology history. Across all sites, the study will enrol 420 couples into the suppression phase. The Couples Counselling Clinic will aim to enrol 60 couples into the suppression phase.Questionnaires will be administered during the study in the Couples Counselling Clinic, with the exception of the 7-Day Validated Psychosexual Daily Questionnaire that will be completed by the participant at home.  Blood samples for laboratory analyses will be collected at visits throughout each phase of the study for processing at both the central laboratory and at Pathology Lancet Kenya.</p>\n<p>\n <strong>Informed Consent</strong></p>\n<p>\n The principles of informed consent will be implemented according to the Declaration of Helsinki in its currently acknowledged version, ICH Consolidated Good Clinical Practice, KNH/UON Ethics Review committee.   Participants male and female, that agree to voluntarily participate in the study must sign the informed consent form (ICF) prior to study-specific procedures.</p>\n
      • study_title<h1>\n <em><strong><span style=\"font-size:16px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Clinical Evaluation of Daily Application of Nestorone® (NES) and Testosterone (T) Combination Gel for Male Contraception.</span></span></strong></em></h1>\n<h1>\n  </h1>\n
      • laymans_summary<p>\n Forty percent (40%) of preg- nancies globally are un- planned. Many women are unable to use hormonal con- traceptives due to the side effects.  International surveys show that men are interested and willing to use male contracep- tion to support their female partners</p>\n<div>\n Current contraception options available for men are con- doms and vasectomies.</div>\n<div>\n More options are needed to support men in meeting their contraceptive needs.</div>\n<div>\n  </div>\n<div>\n OUR STUDY</div>\n<div>\n We are conducting and international, multicenter clinical trial study for male birth control. Our Mission is to develop safe and effective contraception for men.</div>\n<div>\n The primary objective of our study is to determine contracep- tive efficacy for a couple provided by daily application by the male partner of a gel containing testosterone (T) and Nestorone (NES) .</div>\n<div>\n The couples will be in the study for 2 years to test the safety and efficacy of the study gel</div>\n<div>\n Study Goal:</div>\n<div>\n To develop new forms of birth control for men that are:</div>\n<div>\n • Safe</div>\n<div>\n • Reversible</div>\n<div>\n • May be self-delivered</div>\n<div>\n • Affordable</div>\n<div>\n • Have health benefits for men</div>\n<div>\n  </div>\n<div>\n Study Gel</div>\n<div>\n General requirements for entering the study:</div>\n<div>\n Be heterosexual couple: Male, 18-50 years and fe- male, age 18-34 years.</div>\n<div>\n Sexually active, in a stable, monogamous relationship for at least 1 year and plan to be in the relationship for duration of the study duration.</div>\n<div>\n Willingness to accept a low but unknown risk of con- ceiving a pregnancy for the duration of the study.</div>\n<div>\n Live in Nairobi and its environs</div>\n<div>\n Female Partner:</div>\n<div>\n Have regular menstrual cycles of 21-35 days in duration, when not using hormonal contraception.</div>\n<div>\n Intend to remain in a monogamous relationship with male study partner during study.</div>\n<div>\n Not breastfeeding or pregnant.</div>\n<div>\n  </div>\n<div>\n Male Partner:</div>\n<div>\n Be in good health and of normal height and weight. No current disease ( eg diabetes, HIV, hepatitis).</div>\n<div>\n Able to fast for at least 8 hours during the study prior to blood draws and abstain from sex for 2-7 days prior to scheduled clinic visit.</div>\n<div>\n Able to provide semen sample by masturbation during clinic visits</div>\n<div>\n No history of depression or other serious mental health disorder, including use of an antidepressant</div>\n<div>\n No current or previous excessive alcohol use, illicit drug, including marijuana, or anabolic steroid abuse.</div>\n<div>\n A combination Gel with Nestorone® (NES) and Testos- terone (T) applied daily.</div>\n<div>\n The 5ml of the gel is applied on the upper arms and shoulders daily.</div>\n
      • short_titleCCNO17 Male contraception study.
      • protocol_noECCT/18/07/01
      • version_no3.0
      • date_of_protocol04-04-2018
      • study_drugNestorone (NES) and Testosterone (T) Combination Gel
      • disease_conditionContraception
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones1
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device1
      • product_type_chemical_nameNES 8 mg/day + T 62 mg/day (NES-8/T-62) gel
      • product_type_medical_device_namemetered pump canisters
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressseshiwanin@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
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      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr Sheila Juliet Eshiwani
      • declaration_date125-06-2018
      • declaration_principal_investigatorDr John Kinuthia
      • declaration_date225-06-2018
      • placebo_presentNo
      • study_objectives<p>\n The overall goal of this study is to develop a hormonal contraceptive method for men that is effective, safe, reversible, self-delivered, user-controlled and affordable. The objective of this study is to determine whether application of a combined gel containing an androgen, Testosterone (T), and a progestin, Nestorone®, applied transdermally once per day will suppress spermatogenesis and be effective as a contraceptive method in healthy couples who wish to avoid pregnancy and are willing to use the method as their primary method of birth control.</p>\n<div>\n Primary objective</div>\n<div>\n The primary objective of the study is to determine the contraceptive efficacy for a couple provided by continued daily application by the male partner of a gel containing testosterone (T) and Nestorone (NES) for a period of 52 weeks (about 12 months).</div>\n<div>\n  </div>\n<div>\n  Secondary objectives</div>\n<div>\n The secondary objectives of the study are to assess safety and acceptability of the NES 8 mg/day + T 62 mg/day (NES-8/T-62) gel.</div>\n<div>\n  </div>\n
      • principal_inclusion_criteria<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" height=\"345\" width=\"568\">\n <tbody>\n <tr>\n <td style=\"width:564px;height:350px;\">\n <p style=\"margin-left:5.15pt;\">\n <strong>Male Partner – Inclusion Criteria</strong>: Men who meet all the following criteria will be eligible for enrollment in the trial:</p>\n <ol>\n <li>\n Good health as confirmed by medical history, physical examination, and clinical laboratory tests of blood and urine at the time of screening;</li>\n <li>\n 18 to 50 years of age, at the enrollment visit;</li>\n <li>\n BMI < 33 kg/m2;</li>\n <li>\n No history of androgen use in the six months prior to the first screening visit;</li>\n <li>\n Agreement to use an effective method of contraception with his female partner during the suppression and recovery phases and then only use the experimental method during the efficacy phase of the study;</li>\n <li>\n In the opinion of the investigator, the male participant is willing and able to comply with the protocol;</li>\n <li>\n The participant is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study’s provisions and has duly signed the informed consent form</li>\n <li>\n <p>\n Sexually active with a female partner (as specified below) with whom he has been in a stable, mutually monogamous relationship for at least 1 year prior to screening and with whom he intends to remain in a relationship for the duration of the study;</p>\n </li>\n <li value=\"9\">\n Normal reproductive state as demonstrated by:\n <ul>\n <li>\n Sperm concentration ≥15 million/mL in two semen samples and with no gross abnormalities of sperm motility and morphology on at least one semen sample assessment;</li>\n <li>\n Screening Testosterone within the study site’s local lab normal reference range for adult men;</li>\n </ul>\n </li>\n <li value=\"10\">\n Willingness to accept a low but unknown risk of conceiving a pregnancy for the duration of the trial.</li>\n </ol>\n <p style=\"margin-left:5.15pt;\">\n <strong>Female Partner – Inclusion Criteria: </strong>Women who meet all the following criteria will be eligible for enrollment in the trial:</p>\n <ol>\n <li>\n Good general health with no chronic medical conditions that result in periodic exacerbations which require significant medical care or are known to affect fertility;</li>\n <li>\n Aged between 18 and 34 years, inclusive, at the enrollment visit;</li>\n <li>\n Have regular menstrual cycles of 21-35 days in duration, per patient report, when not using hormonal contraception. If hormonal contraception has been used, the following applies:\n <ol style=\"list-style-type:lower-alpha;\">\n <li>\n If recently used intramuscular Depo-Provera must have had last injection at least 3 months prior enrollment;</li>\n <li>\n If using an IUD or an implant, she is planning to have this removed for purposes unrelated to enrollment in the study prior to entering the efficacy phase;</li>\n <li>\n Completion of her last pack of oral contraceptives or completion of effectiveness period for a monthly injection, patch or ring if any has been used prior to entering the efficacy phase;</li>\n </ol>\n </li>\n <li>\n Have intact uterus and both ovaries (waivers for women who have one ovary may be submitted so that the circumstances related to prior ovarian removal can be assessed);</li>\n <li>\n The participant is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study’s provisions and has duly signed the informed consent form (ICF);</li>\n <li>\n Consistent use of effective contraception during the preceding cycle prior to enrolling;</li>\n <li>\n No known infertility;</li>\n <li>\n Intends to remain in a monogamous relationship with male study partner (as specified above). (Note: this study will not provide her contraception for intercourse with any other male partners);</li>\n <li>\n Be at risk for pregnancy with participating male partner (heterosexual vaginal intercourse at least once per cycle and not sterilized);</li>\n </ol>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" height=\"626\" width=\"566\">\n <tbody>\n <tr>\n <td style=\"width:145px;height:877px;\">\n <p>\n  </p>\n <p>\n  </p>\n </td>\n <td style=\"width:564px;height:877px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p style=\"margin-left:5.15pt;\">\n <strong>Male Partner  </strong>Men who meet any of the following criteria are not eligible for enrollment in the trial:</p>\n<p style=\"margin-left:59.15pt;\">\n 1.            Men participating in another clinical trial involving an investigational drug within the last 30 days (or within five half-lives of the investigational drug, whichever is longer) prior to the first screening visit.</p>\n<p style=\"margin-left:59.15pt;\">\n 2.            Men not living in the catchment’s area of the study site or within a reasonable distance from the site.</p>\n<p style=\"margin-left:59.15pt;\">\n 3.            Clinically significant abnormal findings at screening per the Investigator’s medical judgment.</p>\n<p style=\"margin-left:59.15pt;\">\n 4.            Elevated PSA levels ≥ 4 ng/mL.</p>\n<p style=\"margin-left:59.15pt;\">\n 5.            Abnormal serum chemistry values that may indicate clinically significant liver or kidney dysfunction.</p>\n<p style=\"margin-left:59.15pt;\">\n 6.            Use of androgens or other anabolic steroids that may suppress gonadotropins within 6 months prior to the first screening visit.</p>\n<p style=\"margin-left:59.15pt;\">\n 7.            Diastolic blood pressure (DBP) ≥ 85 and Systolic blood pressure (SBP) ≥ 135 mm Hg; (BP will be taken three times at approximately 5 minute intervals and the mean of the 3 measurements will be used to determine eligibility).</p>\n<p style=\"margin-left:59.15pt;\">\n 8.            History of hypertension, including hypertension controlled with treatment.</p>\n<p style=\"margin-left:59.15pt;\">\n 9.            Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis.</p>\n<p style=\"margin-left:59.15pt;\">\n 10.          Known hypersensitivity to progestins or testosterone or any excipient of the investigational product.</p>\n<p style=\"margin-left:59.15pt;\">\n 11.          History of prostate, testicular or breast carcinoma.</p>\n<p style=\"margin-left:59.15pt;\">\n 12.          Significant prostatic symptoms (IPSS > 15).</p>\n<p style=\"margin-left:59.15pt;\">\n 13.          Known history of reproductive dysfunction including vasectomy or infertility.</p>\n<p style=\"margin-left:59.15pt;\">\n 14.          Known history of significant cardiac, renal, hepatic or prostatic disease.</p>\n<p style=\"margin-left:59.15pt;\">\n 15.          History of thromboembolic disease.</p>\n<p style=\"margin-left:59.15pt;\">\n 16.          A serious systemic disease such as diabetes mellitus (including diabetes controlled with treatment), HIV, or morbid obesity.</p>\n<p style=\"margin-left:59.15pt;\">\n 17.          Current active or ongoing Hepatitis infection.</p>\n<p style=\"margin-left:59.15pt;\">\n 18.          History of untreated sleep apnea.</p>\n<p style=\"margin-left:59.15pt;\">\n 19.          Known or suspected current alcohol dependence syndrome, chronic marijuana use, or any illicit drug use that may affect metabolism/transformation of steroid hormones and study treatment compliance.</p>\n<p style=\"margin-left:59.15pt;\">\n 20.          Any known active or chronic dermatitis or other severe skin disorder.</p>\n<p style=\"margin-left:59.15pt;\">\n 21.          Any skin condition that might interfere with absorption of gel.</p>\n<p>\n Couples           desiring            fertility within   the       study   participation     period (approximately 104 weeks from screening to end of recovery).</p>\n<p style=\"margin-left:59.15pt;\">\n 23.          PHQ9 score ≥15 or history of severe depression or other serious mental health disorder, including ongoing use of an anti-depressant.</p>\n<p style=\"margin-left:59.15pt;\">\n 24.          Men participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine. Exclusion is due to the potential of testing positive for androgens that may occur from their study participation coupled with the unknown efficacy (i.e. duration of positive testing) of a single application.</p>\n<p style=\"margin-left:59.15pt;\">\n 25.          Use of sex steroids or medications which might interfere with steroid metabolism (i.e. ketoconazole, finasteride, oral corticosteroids, dutasteride and statins).</p>\n<p style=\"margin-left:59.15pt;\">\n 26.          Use of anticoagulants.</p>\n<p style=\"margin-left:59.15pt;\">\n 27.          Use of medications that will interfere or interact with Nestorone or Testosterone (see <strong>Appendix 2</strong>).</p>\n<p style=\"margin-left:59.15pt;\">\n 28.          Use of oily cosmetic skin gels/products that would prevent absorption of steroids.</p>\n<p style=\"margin-left:59.15pt;\">\n 29.          Previous participation in this clinical trial.</p>\n<p style=\"margin-left:59.15pt;\">\n 30.          Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.</p>\n<p>\n  </p>\n<p style=\"margin-left:5.15pt;\">\n <strong>Female Partner – Exclusion Criteria:</strong></p>\n<p style=\"margin-left:59.15pt;\">\n 1.            Desire to become pregnant during the study.</p>\n<p style=\"margin-left:59.15pt;\">\n 2.            Breastfeeding.</p>\n<p style=\"margin-left:59.15pt;\">\n 3.            Known or suspected current alcoholism or drug abuse.</p>\n<p style=\"margin-left:59.15pt;\">\n 4.            Participation in another clinical trial involving an investigational drug within the last 30 days prior to the first screening visit.</p>\n<p style=\"margin-left:59.15pt;\">\n 5.            Currently pregnant.</p>\n<p style=\"margin-left:59.15pt;\">\n 6.            Known hypersensitivity to progestins or testosterone.</p>\n<p style=\"margin-left:59.15pt;\">\n 7.            History associated with impaired fertility (e.g. history of pelvic inflammatory disease, unilateral salpingectomy or endometriosis).</p>\n<p style=\"margin-left:59.15pt;\">\n 8.            Previous participation in this clinical trial.</p>\n<p>\n Any site staff member with delegated study responsibilities or a family member of a site staff member with delegated study responsibilities.</p>\n
      • primary_end_points<p>\n Twelve-month (365 days) cumulative contraceptive efficacy in couples, during the efficacy portion of the study, in which the male partner uses the product daily to suppress sperm production and the couple uses the method as their sole contraceptive method is the primary endpoint for this study. Kaplan-Meier methods will be used to estimate the twelve-month cumulative pregnancy probability (and 95% CI) in the typical use population </p>\n
      • scope_diagnosis0
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      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyAcceptability
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
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      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p class=\"MsoNormal\" style=\"margin-top:0cm;margin-right:.1pt;margin-bottom:9.55pt;\nmargin-left:0cm\">\n <b style=\"mso-bidi-font-weight:normal\"><span lang=\"EN-GB\">Study Site</span></b></p>\n<p class=\"MsoNormalCxSpMiddle\" style=\"margin-right:.1pt;mso-add-space:auto;\nline-height:150%\">\n <span lang=\"EN-GB\" style=\"color:black\">The</span><span lang=\"EN-GB\"> study will be located in our research clinic at Kenyatta National Hospital, located in the Couples Counselling Center. The Couple Counselling Center was founded in 2004 as a research study site by the Kenyatta National Hospital in collaboration with University of Washington. </span></p>\n<p class=\"MsoNormalCxSpMiddle\" style=\"margin-right:.1pt;mso-add-space:auto;\nline-height:150%;tab-stops:163.5pt\">\n <span lang=\"EN-GB\"><span style=\"mso-tab-count:\n1\">                                                       </span></span></p>\n<p class=\"MsoNormalCxSpLast\" style=\"margin-right:.1pt;mso-add-space:auto;\nline-height:150%\">\n <span lang=\"EN-GB\">The Couple Counselling Center has the following facilities to support conduct of research:</span></p>\n<p class=\"MsoListParagraphCxSpFirst\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span lang=\"EN-GB\"><span style=\"mso-list:Ignore\">1.<span new=\"\" style=\"font:7.0pt \" times=\"\">     </span></span></span><span lang=\"EN-GB\">Two reception areas</span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span lang=\"EN-GB\"><span style=\"mso-list:Ignore\">2.<span new=\"\" style=\"font:7.0pt \" times=\"\">     </span></span></span><span lang=\"EN-GB\">Six consultation/data collection rooms</span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span lang=\"EN-GB\"><span style=\"mso-list:Ignore\">3.<span new=\"\" style=\"font:7.0pt \" times=\"\">     </span></span></span><span lang=\"EN-GB\">Data management room</span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span lang=\"EN-GB\"><span style=\"mso-list:Ignore\">4.<span new=\"\" style=\"font:7.0pt \" times=\"\">     </span></span></span><span lang=\"EN-GB\">Pharmacy </span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span lang=\"EN-GB\"><span style=\"mso-list:Ignore\">5.<span new=\"\" style=\"font:7.0pt \" times=\"\">     </span></span></span><span lang=\"EN-GB\">Procedure room that will be used for semen collection.<span style=\"mso-spacerun:yes\">  </span></span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"text-indent: -18pt; line-height: 150%; margin-left: 54pt;\">\n The study will employ the following staff;</p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span style=\"color:#ff0000;\"><strong><span lang=\"EN-GB\"><span style=\"background-color:#ffff00;\">Site staff, names , qualifications and Experience</span></span></strong></span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span style=\"color:#ff0000;\"><strong><span lang=\"EN-GB\"><span style=\"background-color:#ffff00;\">1 study coordinator</span></span></strong></span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span style=\"color:#ff0000;\"><strong><span lang=\"EN-GB\"><span style=\"background-color:#ffff00;\">2 Clinical officer</span></span></strong></span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span style=\"color:#ff0000;\"><strong><span lang=\"EN-GB\"><span style=\"background-color:#ffff00;\">1 nurse</span></span></strong></span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span style=\"color:#ff0000;\"><strong><span lang=\"EN-GB\"><span style=\"background-color:#ffff00;\">2 Recruitment and retention Officers</span></span></strong></span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span style=\"color:#ff0000;\"><strong><span lang=\"EN-GB\"><span style=\"background-color:#ffff00;\">1 data clerk</span></span></strong></span></p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-left:54.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:150%;mso-list:l0 level1 lfo1\">\n <span style=\"color:#ff0000;\"><strong><span lang=\"EN-GB\"><span style=\"background-color:#ffff00;\">I Study administrator</span></span></strong></span></p>\n<p class=\"MsoNormalCxSpFirst\" style=\"margin-right:.1pt;mso-add-space:auto;\nline-height:150%\">\n <span lang=\"EN-GB\">Several studies involving couples have been conducted at the Couples Counselling Centre including <span style=\"mso-spacerun:yes\"> </span><span style=\"mso-spacerun:yes\"> </span>women’s reproductive lifecourse events and HIV transmission potential: The clinic is currently a Prevention and Care and treatment center for HIV affected couples and is also a site for the Impact of Periconceptual Vaginal Microbiota on Women’s Risk of Preterm Birth Study that is currently ongoing.  </span></p>\n<p>\n <strong>Laboratory procedures </strong></p>\n<p>\n Blood samples for laboratory analyses will be collected at visits throughout each phase of the study for processing at both the central laboratory and at Pathology Lancet Kenya. (Please see page 38-41 of the main study protocol ).</p>\n<p>\n <span lang=\"EN-GB\" style=\"color:black\">Pathologists Lancet Kenya Limited is part of the Lancet Group of Laboratories, originally founded in South Africa. <span style=\"mso-spacerun:yes\"> </span>The Main Laoratory in Nairobi is located at 5th Avenue Office Suites just opposite traffic headquarters.<span style=\"mso-spacerun:yes\">  </span><span style=\"mso-spacerun:yes\"> </span>T</span><span lang=\"EN-GB\">he laboratory is about 1.3kilometres from the Couple Counselling Center. </span></p>\n<p class=\"MsoNormalCxSpMiddle\" style=\"line-height:150%\">\n <span lang=\"EN-GB\" style=\"color:black\">The Pathologists Lancet Kenya will perform laboratory-screening tests for the determination of study eligibility of the participants. This include semen analysis, complete blood counts, clinical chemistry panel, full lipid panel and prostatic specific antigen.<span style=\"mso-spacerun:yes\">  </span></span></p>\n<p class=\"MsoNormalCxSpMiddle\" style=\"line-height:150%\">\n <span lang=\"EN-GB\" style=\"color:black\">Pathologists Lancet Kenya andrology department received SANAS accreditation in 2017. The department has two trained technologists who handle the semen samples. The laboratory runs about 100 semen lysis samples every month. 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      • other_details_explanation
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Kenyatta  National Hospital/ University of Nairobi Ethical review Comittee.  KNH/UoN ERC</p>\n<p>\n University of Washington Institutional Review Board (IRB)</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration3years
      • design_controlled_randomisedNo
      • design_controlled_openYes
      • design_controlled_single_blindYes
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorNo comparator
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaCouples counselling Center
      • single_site_physical_addressKenyatta National Hospital
      • single_site_contact_personDr John Kinuthia
      • single_site_telephone0722799052
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites
      • multi_country_list1)United States of America\nLos angeles biomedical Research Institute at Harbor- UCLA Medical\nUniversity of Washington\nUniversity of Kansas\n2)Chile, Chilean Institute of Reproductive Medicine, Santiago.\n3) Sweden Karolinsk Institute, Stockholm.\n4) United Kingdom, University of Manchester.\nUniversity of Edinburgh \n5)Italy, University of Bologna\n6) Kenya, Kenyatta National Hospital.\n
      • data_monitoring_committeeYes
      • total_enrolment_per_site40-70
      • total_participants_worldwide420
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female0
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Sheila
      • investigator1_middle_name
      • investigator1_family_nameEshiwani
      • investigator1_qualificationMBChB
      • investigator1_professional_addressPO BOX 30681 00100
      • investigator1_telephone0721236111
      • investigator1_emailseshiwanin@gmail.com
      • organisations_transferred_Yes
      • number_participants40-70
      • notification
      • approval_date19-11-2018
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-08-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-04-11 10:18:49
      • created2018-05-02 10:17:50
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id420
        • application_id669
        • given_nameDr John
        • middle_name
        • family_name Kinuthia
        • qualificationMBChB, MMed Obs/gyn MPH
        • professional_addressPO Box 20273-00202,Kenyatta National Hospital
        • telephone0722799052
        • emailkinuthia@uw.edu
        • created2018-05-02 10:53:03
        • modified2020-08-18 14:32:20
    • SiteDetail(array)
      • 0(array)
        • id537
        • application_id669
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2018-05-02 10:53:03
        • modified2020-08-18 14:32:20
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id335
        • application_id669
        • sponsorNational Institute of Health NIH (Eunice Shriver National institute of childhealth and human development NICHD
        • sponsor_typeResearch Institution
        • contact_personDr Jill Long
        • address6710B ROCKLEDGE DRIVE
        • telephone_number+13014961662
        • fax_number
        • cell_number+13014961662
        • email_addressjill.long@nih.gov
        • created2018-05-02 10:53:03
        • modified2020-08-18 14:32:20
      • 1(array)
        • id342
        • application_id669
        • sponsorPopulation Council.
        • sponsor_typeResearch Institution
        • contact_personDr Regine Sitruk-Ware
        • address1230 york avenue, New york,NY 10065 USA
        • telephone_number+13014961662
        • fax_number
        • cell_number+13014961662
        • email_addressfsitrukware@popcouncil.org
        • created2018-05-25 11:37:33
        • modified2020-08-18 14:32:20
  • 1(array)
    • Application(array)
      • id1335
      • user_id73
      • trial_status_id7
      • abstract_of_study<p>\n Topical microbicides are agents designed to prevent or at least substantially reduce the risk of sexual acquisition and transmission of HIV when applied to the genital or rectal mucosa. Vaginal films are an attractive dosing option for topical (vaginal) delivery of anti-HIV drugs. In terms of costs of production and manufacturing, films are relatively inexpensive, scalable, physically, and chemically stable, and amenable to a range of active ingredients including combinations of excipients. In terms of use, films are discreet, portable, and easy to store. Vaginal films can deliver fixed doses of pharmacologically active agents with minimal mess or leakage and without an applicator. Due to their small volume, films also generate no significant alterations in innate microbiome and incur less dilution of endogenous antiviral or antibacterial properties in vaginal fluids as compared to vaginal gels.</p>\n<p>\n The long-term goal of the VALUE (Vaginal film as A Low-cost, User-administered, and Extended-release product) project is to develop and evaluate an extended-release vaginal film containing dapivirine, a potent NNRTI, which could provide protection from HIV for at least one month following a single application.</p>\n
      • study_title<div>\n Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal Films (MATRIX-002)</div>\n
      • laymans_summary<p>\n Topical microbicides are agents designed to prevent or at least substantially reduce the risk of sexual acquisition and transmission of HIV when applied to the genital or rectal mucosa. Vaginal films are an attractive dosing option for topical (vaginal) delivery of anti-HIV drugs.</p>\n<p>\n The long-term goal of the VALUE (Vaginal film as A Low-cost, User-administered, and Extended-release product) project is to develop and evaluate an extended-release vaginal film containing dapivirine, which could provide protection from HIV for at least one month following a single application.</p>\n<p>\n The main aim of this clinical trial is to assess the acceptability and safety of two vaginal placebo films that differ in shape. The proposed study will evaluate the acceptability, safety, and self-insertion success as well as topics relevant to adherence and preference of these 1-month placebo film products when applied vaginally with and without sex. The study will also explore the attitudes and experiences of sexual partners with the vaginal film.</p>\n
      • short_titleVALUE Placebo Film Study
      • protocol_noECCT/23/10/08
      • version_no1.0
      • date_of_protocol24-05-2023
      • study_drugNone
      • disease_conditionHIV
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_namePlacebo Vaginal Film
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressregulatory@pipsthika.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantProf. Nelly Rwamba Mugo
      • declaration_date125-10-2023
      • declaration_principal_investigatorProf. Nelly Rwamba Mugo
      • declaration_date225-10-2023
      • placebo_presentYes
      • study_objectives<p>\n <strong>Primary Objective</strong></p>\n<p>\n <strong>Acceptability</strong></p>\n<ul>\n <li>\n To assess the acceptability of two placebo film types (A and B) when administered vaginally once monthly for two months.</li>\n</ul>\n<p>\n <strong>Secondary Objectives</strong></p>\n<p>\n <strong>Safety</strong></p>\n<ul>\n <li>\n To assess the safety of two placebo film types (A and B) when administered vaginally once monthly for two months.</li>\n</ul>\n<p>\n <strong>Usability</strong></p>\n<ul>\n <li>\n To assess participants’ ability to properly insert the placebo vaginal film.</li>\n</ul>\n<p>\n <strong>Exploratory Objectives</strong></p>\n<p>\n <strong>Participant acceptability, attitudes and experiences</strong></p>\n<ul>\n <li>\n To explore multiple dimensions of acceptability of two placebo film types (A and B) and participants’ attitudes towards and experiences with the vaginal film.</li>\n</ul>\n<p>\n <strong>Sexual partner attitudes and experiences</strong></p>\n<ul>\n <li>\n To explore sexual partners’ attitudes towards and experiences with the vaginal film.</li>\n</ul>\n<p>\n <strong>Vaginal microenvironment</strong></p>\n<ul>\n <li>\n To assess the impact of placebo film use on participants’ vaginal microenvironment when administered vaginally once monthly for two months.</li>\n</ul>\n<p>\n <strong>Social harms and social benefits</strong></p>\n<ul>\n <li>\n To describe the reported experiences of social harms and social benefits over the course of vaginal film use.</li>\n</ul>\n
      • principal_inclusion_criteria<h3>\n Study Participants</h3>\n<ol>\n <li>\n Aged 18 to 45 years (inclusive).</li>\n</ol>\n<ol>\n <li value=\"2\">\n Assigned female sex at birth.</li>\n</ol>\n<ol>\n <li value=\"3\">\n Able and willing to provide written informed consent to be screened for and enrolled in MATRIX-002 in one of the study languages.</li>\n</ol>\n<ol>\n <li value=\"4\">\n Able and willing to provide adequate contact/locator information, as defined in site SOP.</li>\n</ol>\n<ol>\n <li value=\"5\">\n Able and willing to comply with all protocol requirements, including:</li>\n</ol>\n<ul>\n <li>\n Abstaining from all receptive sexual intercourse (vaginal, anal, digital, oral) for the first month of product use.</li>\n <li>\n Abstaining from using other intravaginal products for the first month of product use.</li>\n <li>\n Abstaining from engaging in intravaginal practices for the first month of product use.</li>\n <li>\n Refraining from participation in other research studies for the duration of the study unless approved by the Protocol Safety Review Team (PSRT).</li>\n <li>\n Responding to scheduled phone/short message service (SMS) contacts.</li>\n <li>\n Attending all clinic follow-up visits.</li>\n</ul>\n<ol>\n <li value=\"6\">\n HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithms in Appendix II).</li>\n</ol>\n<ol>\n <li value=\"7\">\n Per participant report, if in a relationship, must be in a mutually monogamous relationship with a partner who is not known to be HIV positive or to currently have a sexually transmitted infection (STI).</li>\n</ol>\n<ol>\n <li value=\"8\">\n Negative urine pregnancy test at Screening and Enrollment.</li>\n</ol>\n<ol>\n <li value=\"9\">\n Participants over the age of 21 (inclusive) must have documentation of a Grade 0 Pap smear within the past 3 years prior to Enrollment, or a Grade 1 Pap smear at Screening with no treatment required, per the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated November 2007) to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.</li>\n</ol>\n<ol>\n <li value=\"10\">\n Protected from pregnancy starting two weeks before Screening and continuing for the duration of study participation by an effective contraceptive method as confirmed by site SOP; effective methods include:</li>\n</ol>\n<ul>\n <li>\n Hormonal methods except vaginal rings</li>\n <li>\n Copper intrauterine device (IUD)</li>\n <li>\n Sterilization of participant</li>\n <li>\n Correct and consistent condom use (for US site only)</li>\n <li>\n Abstinence from penile-vaginal intercourse</li>\n</ul>\n<h3>\n Sexual Partners</h3>\n<p>\n Potential participants for the sexual partner IDI subset must meet all of the following criteria to be eligible for inclusion in the study:</p>\n<ol>\n <li>\n Identifies as a sexual partner of a MATRIX-002 participant.</li>\n <li>\n Identified by participant as a sexual partner during MATRIX-002 for whom the participant has given permission to contact (as specified in site SOP).</li>\n <li>\n Able and willing to provide written informed consent in one of the study languages (as specified in site SOP).</li>\n <li>\n Able and willing to complete the required study procedures.</li>\n <li>\n Must be 18 years old or above at the time of their study participation, verified per site SOP.</li>\n</ol>\n
      • principal_exclusion_criteria<ol>\n <li>\n Per participant report at Screening and Enrollment, intends to do any of the following during the study participation period:</li>\n</ol>\n<ul>\n <li>\n Become pregnant.</li>\n <li>\n Breastfeed.</li>\n <li>\n Relocate away from the study site.</li>\n <li>\n Travel away from the study site for a time period that would interfere with product resupply and/or study participation.</li>\n</ul>\n<ol>\n <li value=\"2\">\n Positive HIV test at Screening or Enrollment.</li>\n</ol>\n<ol>\n <li value=\"3\">\n Positive test for <em>Trichomonas vaginalis</em> (TV), <em>Neisseria gonorrhea </em>(GC), <em>Chlamydia trachomatis</em> (CT), or <em>Treponema pallidum</em> (Syphilis) at Screening or (per participant report) treated for potential STI within past 12 months.</li>\n</ol>\n<ol>\n <li value=\"4\">\n Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), or reproductive tract infection (RTI) requiring treatment per WHO guidelines at Enrollment.</li>\n</ol>\n<ol>\n <li value=\"5\">\n Clinically apparent Grade 2 or higher pelvic exam finding per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1 (Female Genital  Grading Table for Use in Microbicide Studies [Dated November 2007]) at Enrollment.</li>\n</ol>\n<ol>\n <li value=\"6\">\n Participant report and/or clinical evidence of any of the following:</li>\n</ol>\n<ul>\n <li>\n Known adverse reaction to any of the study product materials (ever).</li>\n <li>\n Hysterectomy.</li>\n <li>\n Surgical procedure involving the pelvis in the 30 days prior to Enrollment.</li>\n <li>\n Use of diaphragm, NuvaRing, or (for African sites only) spermicide for contraception in the two weeks prior to Screening.</li>\n <li>\n Antibiotic or antifungal (oral or intravaginal) therapy within 7 days of Enrollment.</li>\n <li>\n Prior use of post-exposure prophylaxis (PEP) or oral pre-exposure prophylaxis (PrEP) (including FTC/TDF) in the 4 weeks prior to Screening or any prior use of long-acting systemic PrEP (including cabotegravir or islatravir).</li>\n <li>\n Use of any of the following in the 12 months prior to Screening: stimulants (cocaine [including crack], methamphetamine, or non-physician prescribed pharmaceutical-grade stimulants), or inhaled nitrates, or illicit injection drug use of any kind.</li>\n <li>\n At Screening or Enrollment, as determined by the Investigator of Record (IoR)/designee, has any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease.</li>\n</ul>\n<ol>\n <li value=\"7\">\n Has any of the following laboratory abnormalities at Screening:</li>\n</ol>\n<ul>\n <li>\n Grade 2 or higher Aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine, or Hemoglobin per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.</li>\n</ul>\n<ol>\n <li value=\"8\">\n Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.</li>\n</ol>\n
      • primary_end_points<p>\n <strong>Primary Endpoints:</strong></p>\n<p>\n <strong>Acceptability</strong></p>\n<ul>\n <li>\n Participant ratings of overall satisfaction with using the placebo vaginal films.</li>\n</ul>\n<p>\n <strong>Secondary Endpoints:</strong></p>\n<p>\n <strong>Safety</strong></p>\n<ul>\n <li>\n Proportion of participants with genitourinary Grade 2 or higher Adverse Events deemed related to study product.</li>\n</ul>\n<p>\n <strong>Usability</strong></p>\n<ul>\n <li>\n Proportion of participants with clinically assessed proper insertion (more than half of the vaginal film proximal to introitus).</li>\n</ul>\n<p>\n <strong>Exploratory Endpoints:</strong></p>\n<p>\n <strong>Participant acceptability, attitudes and experiences</strong></p>\n<ul>\n <li>\n Participant responses to quantitative acceptability assessments and IDI questions. Multiple dimensions will be explored, including:\n <ul>\n <li>\n Vaginal film attributes, including acceptability (e.g., ease of insertion, burden, perceived effectiveness of film as delivery form) and preferences</li>\n <li>\n Experience and comfort with inserted vaginal film (e.g., expulsions, leakage, awareness of film during daily activities)</li>\n <li>\n Experience during sex and menses</li>\n <li>\n Vaginal practices and concomitant vaginal product use while using vaginal film</li>\n <li>\n Perception of sexual partners’ attitudes towards vaginal film</li>\n <li>\n Perceived benefits and concerns/challenges with the vaginal film as a future HIV prevention option</li>\n <li>\n Interest in using vaginal film as a future HIV prevention option</li>\n </ul>\n </li>\n</ul>\n<p>\n <strong>Sexual partner attitudes and experiences</strong></p>\n<ul>\n <li>\n Sexual partner responses during IDI related to:\n <ul>\n <li>\n Vaginal film attributes, including acceptability and preferences</li>\n <li>\n Perception of participant’s experience using the vaginal film during the study</li>\n <li>\n Physical sensation of the participant’s vaginal film use during sex (as relevant)</li>\n <li>\n Perceived benefits and concerns/challenges with the vaginal film as a future HIV prevention option</li>\n </ul>\n </li>\n</ul>\n<p>\n <strong>Vaginal microenvironment</strong></p>\n<ul>\n <li>\n Change from baseline in vaginal pH following film use during the two study phases (i.e., with and without sexual abstinence requirement).</li>\n <li>\n Change from baseline in quantity of selected vaginal microbiota following film use during the two study phases (i.e., with and without sexual abstinence requirement).</li>\n <li>\n Change from baseline in Nugent score following film use during the two study phases (i.e., with and without sexual abstinence requirement).</li>\n</ul>\n<p>\n <strong>Social harms and social benefits</strong></p>\n<ul>\n <li>\n Participant self-report of social harms (i.e., non-clinical adverse consequences of study participation or product use that may manifest in social, psychological or physical ways).</li>\n <li>\n Participant and sexual partner self-report of social benefits (e.g., positive consequences of product use disclosure, self-confidence, improved communication with intimate partner) resulting from vaginal film use and/or study participation.</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyAcceptability
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyAssess Acceptability and Safety of Two Placebo Prototype Vaginal Films
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n KEMRI-CCR Partners in Health & Research Development - PHRD (Formerly Partners in Prevention) Thika Project, has 109 full time clinical trial staff (including physicians, nurses, counsellors, pharmacist, pharmaceutical technologists, clinical officers, social scientists, administrative staff etc).</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Principal Investigator: Prof. Nelly R. Mugo  MBChB,MMED,MPH</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Site Principal Investigator: Prof. Kenneth Ngure  BSc,MPH,MSc,PhD</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Site Coordinator: Dr. Catherine Kiptinness, BPharm, MPH</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Study Coordinator: Dr. Betty Njoroge, MBChB, MPH</p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">The study will be conducted in both Kenya and the host country of the sponsor.</span></p>\n
      • other_details_regulatory_notapproved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Pan African Clinical Trials Registry - </span></p>\n
      • other_details_regulatory_approved<p>\n Kenya Medical Reseearch Institute Scientific and Ethics Review Unit (KEMRI SERU)</p>\n<p>\n Approval date: 05 October 2023</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration12 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-CCR PHRD Thika
      • single_site_physical_addressThika Section 9, OAU Road
      • single_site_contact_personProf. Nelly Rwamba Mugo
      • single_site_telephone+254723914057
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_statesFour
      • number_of_sites
      • multi_country_list1. Kenya\n2. Zimbabwe\n3. South Africa\n4. USA
      • data_monitoring_committeeNo
      • total_enrolment_per_site20
      • total_participants_worldwide100
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameNelly
      • investigator1_middle_nameRwamba
      • investigator1_family_nameMugo
      • investigator1_qualificationMBChB, MMED, MPH
      • investigator1_professional_addressKEMRI-CCR
      • investigator1_telephone+254723914057
      • investigator1_emailrwamba@uw.edu
      • organisations_transferred_Yes
      • number_participants20
      • notification
      • approval_date17-01-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-10-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed comprehensively.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-12-17 17:41:15
      • created2023-10-17 10:41:12
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id987
        • application_id1335
        • given_nameNelly
        • middle_nameRwamba
        • family_nameMugo
        • qualificationMBChB, MMED, MPH
        • professional_addressKEMRI-CCR
        • telephone+254723914057
        • emailrwamba@uw.edu
        • created2023-10-17 10:55:00
        • modified2023-10-25 13:40:49
    • SiteDetail(array)
      • 0(array)
        • id1612
        • application_id1335
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2023-10-17 10:55:00
        • modified2023-10-25 13:40:49
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id701
        • application_id1335
        • sponsorMATRIX Clinical Trials Hub
        • sponsor_typeOthers
        • contact_person
        • addressMagee-Women’s Research Institute and Foundation (MWRIF), 204 Craft Avenue, Pittsburgh, PA 15213 USA
        • telephone_number+1-412-641-6435
        • fax_number
        • cell_number+1-412-641-6435
        • email_addresshillsl@mwri.magee.edu
        • created2023-10-17 10:55:00
        • modified2023-10-25 13:40:49
  • 2(array)
    • Application(array)
      • id1369
      • user_id622
      • trial_status_id1
      • abstract_of_study<p>\n <strong>Protocol Number: CO44657</strong></p>\n<p>\n <strong>Study Name: pionERA</strong></p>\n<p>\n <strong>Version Number: 1</strong></p>\n<p>\n <strong>Test Compound: Giredestrant (RO7197597)</strong></p>\n<p>\n The proposed Phase III study is designed to demonstrate a statistically significant and clinically meaningful progressionfree survival (PFS) benefit of giredestrant compared with fulvestrant, each combined with the investigator's choice of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) between palbociclib, abemaciclib and ribociclib, as first-line (1L) treatment of estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer (aBC) resistant to adjuvant endocrine therapy (ET), a patient group considered to have a particularly high unmet need. The proposed enrichment strategy in ESR1 mutation (ESR1m) allows assessment of the co-primary endpoints in the ESR1m subgroup, who have worse prognosis and who are more likely to derive the greatest benefit from novel oral selective estrogen receptor-<b style=\"color: rgb(32, 33, 36); font-family: "Google Sans", arial, sans-serif; font-size: 14px;\">α</b> antagonists and degraders (SERDs) like giredestrant, and in the full study population, inclusive of participants without an ESR1 mutation detected (ESR1nmd).</p>\n<p>\n  </p>\n<div>\n Participants in the experimental arm will receive giredestrant 30 mg orally (PO) once a day (QD) on Days 1−28 of each 28-day cycle. Giredestrant will be administered in the clinic on Day 1 of Cycle 1, and on Day 1 of each 28-day cycle thereafter, as indicated in the schedule of activities; it will be taken at home on all non-clinic visit days. Participants in the control arm will receive intramuscular (IM) fulvestrant 500 mg IM on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle. In both arms of the study, all participants will receive the investigator’s choice of CDK4/6i (palbociclib 125 mg or ribociclib 600 mg given PO QD on Days 1−21 of each 28−day cycle, or abemaciclib 150 mg PO twice daily (BID) on Days 1−28 of each 28−day cycle); switching the CDK4/6i for a given patient is not permitted during the study. Modification of the giredestrant dose is not permitted. The dose of abemaciclib, ribociclib, or palbociclib can be reduced up to two times for management of drug-related toxicities. Pre/perimenopausal female and male participants in both arms will also receive a luteinizing hormone-releasing hormone (LHRH) agonist according to local prescribing guidelines. LHRH agonist therapy may be initiated 28 days prior to Day 1 of Cycle 1 (or according to clinical practice for the selected agent) and recommended at least 2 weeks prior to initiation of study treatment. Patients already on one LHRH agonist may remain on the same agent without switching.</div>\n<div>\n  </div>\n<div>\n <strong>Number of patients</strong></div>\n<div>\n Approximately 10 patients (5 on Giredestrant, 5 on Fulvestrant)</div>\n<div>\n  </div>\n<div>\n <strong>End of Study:</strong></div>\n<div>\n A participant is considered to have completed the study if he or she has completed all phases of the study, including the last visit or last scheduled procedure shown in the schedule of activities (see Section 1.3 of the protocol).</div>\n<div>\n  </div>\n<div>\n The end of this study is defined as the date of the last visit of the last participant in the study/last scheduled procedure shown in the schedule of activities for the last participant in the study globally (i.e., last participant in the global and potential extended China enrollment phases combined) or the date at which the last data point required for statistical analysis (i.e., see endpoints in Section 3 of the protocol) or safety follow-up is received from the last participant (global and potential extended China enrollment phases combined), whichever occurs later. The end of the study is expected to occur at least 18 months after the last participant is enrolled. In addition, the Sponsor may decide to terminate the study at any time.</div>\n<div>\n  </div>\n<div>\n <strong>Study Duration</strong></div>\n<div>\n The total duration of study participation for each individual is expected to be approximately 40 months (range 1 day to more than 60 months).</div>\n
      • study_title<div>\n This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of</div>\n<div>\n giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor</div>\n<div>\n (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal</div>\n<div>\n growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant</div>\n<div>\n endocrine therapy.</div>\n
      • laymans_summary<p>\n A clinical study to compare giredestrant with fulvestrant, both combined with a targeted therapy (CDK4/6 inhibitor) in people with ER-positive, HER2-negative breast cancer that has come back after adjuvant hormone therapy</p>\n<p>\n This study is recruiting people with ER-positive, HER2-negative breast cancer that is resistant to a previous adjuvant hormone therapy. People can take part if their cancer has or has not got mutated ERs, and has grown (advanced) or spread to other parts of the body (metastatic).</p>\n<p>\n People who take part in this study (participants) will be given the study treatment giredestrant or fulvestrant, both combined with a CDK4/6i (palbociclib, ribociclib or abemaciclib) until their cancer gets worse or they have unacceptable side effects. The study doctor will see them regularly. These hospital visits will include checks to see how the participants respond to the treatment, including any side effects they may have. Total time of participation in the study is expected to be, on average, about 3–5 years, depending on how well treatment works. Participants can stop study treatment and leave the study at any time.</p>\n<p>\n  </p>\n
      • short_titlepionERA
      • protocol_noECCT/24/02/09
      • version_no1
      • date_of_protocol07-07-2023
      • study_drugGiredestrant
      • disease_conditionER-positive, HER2-Negative Advanced Breast Cancer
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameFulvestrant
      • comparator_registeredYes
      • comparator_countriesIn all trial participating countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressfaith.wanjau@roche.con
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantKatrina Budesha
      • declaration_date128-02-2024
      • declaration_principal_investigatorDr Sitna Ali
      • declaration_date228-02-2024
      • placebo_presentYes
      • study_objectives<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <span class=\"term\" data-term=\"primary outcome measure\" style=\"box-sizing: border-box; background-position: left bottom; background-size: 4px 1px; background-repeat: repeat-x; transition: background-color 0s ease 0s, all 0.2s ease 0s, box-shadow 0s ease 0s, all 0.2s ease 0s, color 0s ease 0s, all 0.2s ease 0s; border-bottom: 1px dotted; color: rgb(17, 46, 81); cursor: pointer; display: inline;\" tabindex=\"0\" title=\"Click to define\">Primary Outcome Measures </span> :\n <ol style=\"box-sizing: border-box; margin-top: 1ex; margin-bottom: 1ex;\">\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup [ Time Frame: From randomization to first occurrence of progressive disease (PD) or death (up to 5 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study.</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n PFS in the Full Analysis Set (FAS) Population [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years) ]</li>\n </ol>\n</div>\n<p>\n  </p>\n<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin-right:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <span class=\"term\" data-term=\"secondary outcome measure\" style=\"box-sizing: border-box; background-position: left bottom; background-size: 4px 1px; background-repeat: repeat-x; transition: background-color 0s ease 0s, all 0.2s ease 0s, box-shadow 0s ease 0s, all 0.2s ease 0s, color 0s ease 0s, all 0.2s ease 0s; border-bottom: 1px dotted; color: rgb(17, 46, 81); cursor: pointer; display: inline;\" tabindex=\"0\" title=\"Click to define\">Secondary Outcome Measures </span> :\n <ol style=\"box-sizing: border-box; margin-top: 1ex; margin-bottom: 1ex;\">\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Overall Survival (OS) [ Time Frame: From randomization until death from any cause (up to 5 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n OS is defined as the time from randomization to death from any cause. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Confirmed Objective Response Rate (cORR) [ Time Frame: From randomization until treatment discontinuation (up to 5 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n The cORR is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Duration of Response (DOR) [ Time Frame: From the first occurrence of a documented objective response to PD or death (up to 5 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n DOR is defined as the time from the first occurrence of a documented objective response to PD, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Clinical Benefit Rate (CBR) [ Time Frame: From randomization until treatment discontinuation (up to 5 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n The CBR is defi</div>\n </li>\n </ol>\n</div>\n
      • principal_inclusion_criteria<p 1ex=\"\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n Inclusion Criteria:</p>\n<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; color: rgb(0, 0, 0); font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or archived tumor sample)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Confirmed ESR1 mutation status (ESR1m vs. ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Resistance to prior adjuvant endocrine therapy (ET). Prior use of neo/adjuvant CDK4/6i is allowed.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n No prior systemic anti-cancer therapy for advanced disease</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Measurable disease as defined per RECIST v.1.1 or non-measurable bone-only disease</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n For pre/perimenopausal women and for men: treatment with LHRH agonist therapy (as per local guidelines) for the duration of study treatment is required</li>\n</ul>\n
      • principal_exclusion_criteria<p 0ex=\"\" 0px=\"\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n Exclusion Criteria:</p>\n<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; color: rgb(0, 0, 0); font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Active cardiac disease or history of cardiac dysfunction</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Clinically significant history of liver disease</li>\n</ul>\n
      • primary_end_points<p>\n <span class=\"term\" data-term=\"primary outcome measure\" display:=\"\" font-size:=\"\" helvetica=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; background-position: left bottom; background-size: 4px 1px; background-repeat: repeat-x; transition: background-color 0s ease 0s, all 0.2s ease 0s, box-shadow 0s ease 0s, all 0.2s ease 0s, color 0s ease 0s, all 0.2s ease 0s; border-bottom: 1px dotted; color: rgb(17, 46, 81); cursor: pointer; font-family: \" tabindex=\"0\" title=\"Click to define\">Primary Outcome Measures </span><span font-size:=\"\" helvetica=\"\" sans=\"\" source=\"\" style=\"color: rgb(0, 0, 0); font-family: \"> :</span></p>\n<ol font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" margin-top:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; color: rgb(0, 0, 0); font-family: \">\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup [ Time Frame: From randomization to first occurrence of progressive disease (PD) or death (up to 5 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study.</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n PFS in the Full Analysis Set (FAS) Population [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years) ]</li>\n</ol>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">This information has been provided in the respective Site-specific information/site-specific addendum attached.</span></p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n <span id=\"docs-internal-guid-31362a42-7fff-e4e6-6cf4-14f7531cb855\"><span font-variant-alternates:=\"\" font-variant-east-asian:=\"\" font-variant-numeric:=\"\" font-variant-position:=\"\" style=\"font-size: 11pt; font-family: \" trebuchet=\"\" vertical-align:=\"\" white-space-collapse:=\"\">Colombia (8-Sep), India (3-Oct) also submitted</span></span></p>\n
      • other_details_regulatory_approved<div align=\"left\" dir=\"ltr\" style=\"margin-left:36pt;\">\n <table style=\"border-width: initial; border-style: none; border-color: initial; border-collapse: collapse; table-layout: fixed; width: 468pt;\">\n <colgroup>\n <col />\n <col />\n <col />\n </colgroup>\n <tbody>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Country</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Date of Approval</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-weight: 700; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">No of Sites</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">US</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">08 Aug 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">106</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Canada</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">01 Sep 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">50</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Taiwan</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">12 Sep 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">6</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Korea </span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">21 Sep 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">11</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">New Zealand</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">02 Oct 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">3</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Argentina</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">08 Oct 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">12</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Brazil</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">11 Oct 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">20</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Australia</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">08 Nov 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">14</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">China</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">16 Nov 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">33</span></span></p>\n </td>\n </tr>\n <tr style=\"height:0pt\">\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">Chile</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">16 Nov 2023</span></span></p>\n </td>\n <td style=\"border-left:solid #000000 1pt;border-right:solid #000000 1pt;border-bottom:solid #000000 1pt;border-top:solid #000000 1pt;vertical-align:top;padding:5pt 5pt 5pt 5pt;overflow:hidden;overflow-wrap:break-word;\">\n <p dir=\"ltr\" style=\"line-height:1.2;margin-top:0pt;margin-bottom:0pt;\">\n <span id=\"docs-internal-guid-2833d079-7fff-4746-4690-ef7f9b0cd669\"><span style=\"font-size: 12.5pt; font-family: Roboto, sans-serif; color: rgb(31, 31, 31); background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline; white-space-collapse: preserve;\">7</span></span></p>\n </td>\n </tr>\n </tbody>\n </table>\n</div>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration28-31 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorFulvestrant
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaUniversity of Nairobi -Institute of Tropical and Infectious Diseases
      • single_site_physical_addressFaculty of Health Sciences, P.O. BOX 19676-00202
      • single_site_contact_personDr Sitna Ali
      • single_site_telephone+254717333452
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states37
      • number_of_sites
      • multi_country_listArgentina, Australia, Austria, Belgium. Brazil, Canada, Chile, China, Colombia, Costa Rica, Finland, France, Germany, Greece, Guatemala, Hong King, Hungary, India, Israel, Italy, Kenya, Mexico, New Zealand, Peru, EEA HAs, Poland, Portugal, Romania, Singapore, Slovenia, South Africa, South Korea, Spain, Taiwan, Thauland, Turkey, United States
      • data_monitoring_committeeYes
      • total_enrolment_per_site10
      • total_participants_worldwide1050
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Sitna
      • investigator1_middle_name
      • investigator1_family_nameAli
      • investigator1_qualificationConsultant Medical Oncologist
      • investigator1_professional_addressUniversity of Nairobi -Institute of Tropical and Infectious Diseases
      • investigator1_telephone+254717333452
      • investigator1_emailsitna.ali@gmail.com
      • organisations_transferred_Yes
      • number_participants10
      • notification
      • approval_date04-08-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-05-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted15-03-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-08 13:58:37
      • created2024-01-17 13:44:01
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1035
        • application_id1369
        • given_nameDr Sitna
        • middle_name
        • family_nameAli
        • qualificationConsultant Medical Oncologist
        • professional_addressUniversity of Nairobi -Institute of Tropical and Infectious Diseases
        • telephone+254717333452
        • emailsitna.ali@gmail.com
        • created2024-01-18 16:11:31
        • modified2024-05-07 14:40:19
    • SiteDetail(array)
      • 0(array)
        • id1666
        • application_id1369
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2024-01-18 16:11:31
        • modified2024-05-07 14:40:19
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id720
        • application_id1369
        • sponsorHoffmann La Roche
        • sponsor_typeIndustry
        • contact_personKatrina Budesha
        • addressHexagon Place, Shire Park, Falcon Way, Welwyn Garden City AL7 1TW
        • telephone_number07721051097
        • fax_number
        • cell_number07721051097
        • email_addresskatrina.budesha@roche.com
        • created2024-01-18 16:11:31
        • modified2024-05-07 14:40:19
  • 3(array)
    • Application(array)
      • id963
      • user_id664
      • trial_status_id5
      • abstract_of_study<p>\n Background: The lack of available therapy in conjunction with increasing numbers of global cases indicates that MERS-CoV infection remains a serious unmet medical need. Due to cross-species infection, both human and animal outbreaks are possible. Appropriate measures to prevent, control and treat existing and future infections are needed. The hypothesis of this study is that a selected optimal dose of INO-4700 delivered intradermally (ID) followed by electroporation (EP) using CELLECTRATM 2000 in healthy volunteers will be well tolerated, exhibit an acceptable safety profile and result in generation of immune responses to MERS-CoV.</p>\n<p>\n Methods: This is a Phase 2a, randomized, blinded, placebo-controlled, multi-center trial in healthy adult volunteers. Approximately 542 participants will be evaluated across two (2) parts of this study. In Part 1, 192 participants ages 18-50 years will be assessed through five (5) dose levels and regimens. INO-4700 or placebo (SSC-0001) will be administered ID followed immediately by EP. Participants will be randomized to receive either INO-4700 (160 subjects) or placebo (32 subjects) via one or two injections, followed by EP, at weeks 0 and 4 or weeks 0 and 8. Upon completion of the Week 10 visit, Part 1 will be unblinded in order to allow for one regimen to be selected for advancement into Part 2. The Study Group with an optimal immune response, an acceptable safety profile and tolerant dosing regimen by Week 10 will be selected. All Part 1 participants will be followed for 48 weeks from the Da y 0 dosing. In Part 2, approximately 350 participants ages 18 and older will be evaluated across one (1) dose level and regimen. Part 2 of the study is divided into two parts, Part 2A and 2B. In Part 2A, participants will be randomized to receive INO-4700 (300 participants) or placebo (50 participants). In Part 2B, the first 200 participants randomized to receive INO-4700 in Part 2A will receive a third dose of either INO-4700 or placebo at Week 48. Similarly, in Part 2B, the first 25 participants randomized to receive placebo in Part 2A will receive a third dose of placebo at Week 48. These first 225 participants will be followed for 68 weeks from the Day 0 dosing. All remaining 125 participants will be followed for 48 weeks from the Day 0 dosing. Adverse events will be collected at every visit and safety samples and immunology blood samples will be drawn throughout the study. All adverse events, regardless of relationship, will be collected from the time of consent to 12 weeks from Day 0. Only related adverse events, adverse events of special interest and serious adverse events will be collected thereafter.</p>\n<p>\n  </p>\n
      • study_title<div>\n Study to Evaluate the Safety, Tolerability and Immunogenicity of INO-4700 for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Healthy Volunteers</div>\n
      • laymans_summary<div>\n The vaccine in this clinical trial is an investigational product called INO-4700. INO-4700 will be given with an investigational device, CELLECTRA™ 2000. The CELLECTRATM 2000 device is used to deliver four (4) brief pulses of electricity (called electroporation, or “EP”) to get more of the investigational product into the skin cells. INO-4700 is being developed to protect humans from an illness called Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV) infection. MERS-CoV is an animal-borne (found in Arabian (one hump) camels) infection caused by a virus that is spread from animals to humans. Once humans are infected with this virus, it can also spread from human to human by direct contact. MERS-CoV causes serious respiratory illness in humans.</div>\n<div>\n  </div>\n<div>\n The purpose of this clinical trial is to:</div>\n<div>\n • Test the safety and tolerability (level of discomfort) of the vaccine and the device in healthy volunteers</div>\n<div>\n • Test the effect of the vaccine and the device on the immune system</div>\n<div>\n • Select the most favorable dose</div>\n<div>\n  </div>\n<div>\n Approximately 542 healthy volunteers will participate in this clinical trial. Subjects will be in the study for either 48 weeks or 68 weeks. Subjects will either receive INO-4700 or placebo (a product without medication).</div>\n
      • short_titleMERS-201
      • protocol_noECCT/20/12/02
      • version_no1.0
      • date_of_protocol23-03-2020
      • study_drugINO-4700
      • disease_conditionMiddle East Respiratory Syndrome Coronavirus (MERS-CoV)
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressissatou.diallo@mct-cro.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantBernhards Ogutu
      • declaration_date104-02-2021
      • declaration_principal_investigatorBernhards Ogutu
      • declaration_date204-02-2021
      • placebo_presentYes
      • study_objectives<p>\n <strong>Primary Obejectives</strong>:</p>\n<p>\n Evaluate the tolerability and safety of INO-4700 administered by ID injection followed by EP in healthy adult volunteers</p>\n<p>\n Evaluate the cellular (T cell) and humoral immune response to INO-4700 administered by ID injection followed by EP for identification and confirmation of an optimal dose and regimen</p>\n<p>\n Evaluate selected optimal dose for safety and immunogenicity</p>\n<div>\n <p>\n <strong>Exploratory Objectives</strong>:</p>\n <p>\n Evaluate the expanded immunological profile by assessing both T and B cell immune responses</p>\n <div>\n <p>\n Evaluate the cellular (T cell) and humoral immune response to INO-4700 administered by ID injection followed by EP for impact of boosting with a third dose</p>\n </div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n a. Able to provide informed consent and have signed Informed Consent Form (ICF) prior to screening procedures;</div>\n<div>\n b. For Part 1, adults age 18 and 50 years, inclusive. For Part 2, adults at least 18 years</div>\n<div>\n of age;</div>\n<div>\n c. Judged to be healthy by the Investigator on the basis of medical history, physical examination and vital signs performed at Screening. Note: Participants taking daily prescription or non-prescription medications for management of acceptable chronic</div>\n<div>\n medical conditions must be on a stable dose, as defined by non-change in dose for the 3 months prior to the first dose of study medication and no planned changes during the active dosing period of the study;</div>\n<div>\n d. Able and willing to comply with all study procedures;</div>\n<div>\n e. Screening laboratory results within normal limits for testing laboratory or deemed not clinically significant by the Investigator;</div>\n<div>\n f. Negative serological tests for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody and Human Immunodeficiency Virus (HIV) antibody or rapid test at screening;</div>\n<div>\n g. Screening ECG deemed by the Investigator as having no clinically significant findings (e.g. Wolff-Parkinson-White syndrome);</div>\n<div>\n h. Must meet one of the following criteria with respect to reproductive capacity:</div>\n<div>\n ï‚· Women who are post-menopausal as defined by spontaneous amenorrhea for ≥ 12 months;</div>\n<div>\n ï‚· Surgically sterile or have a partner who is sterile (i.e., vasectomy in males at least six (6) months prior to enrollment or tubal ligation, absence of ovaries and/or uterus in females);</div>\n<div>\n ï‚· Use of medically effective contraception with a failure rate of < 1% per year when used consistently and correctly from screening until 1 month following last dose. Acceptable methods include:</div>\n<div>\n ‒ hormonal contraception including implants, injections or oral;</div>\n<div>\n ‒ two barrier methods, e.g., condom and cervical cap (with spermicide) or diaphragm (with spermicide);</div>\n<div>\n ‒ abstinence when this is the subject’s preferred and usual lifestyle. Note: Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.</div>\n
      • principal_exclusion_criteria<div>\n a. Pregnant or breastfeeding, or intending to become pregnant or father children within the projected duration of the trial starting with the screening visit until 1 month following last dose;</div>\n<div>\n b. Positive serum pregnancy test during screening or positive urine pregnancy test prior to dosing;</div>\n<div>\n c. History of respiratory diseases such as asthma, chronic obstructive pulmonary disease or chronic bronchitis;</div>\n<div>\n d. Is currently participating in or has participated in a study with an investigational product with 30 days preceding Day 0;</div>\n<div>\n e. Previous receipt of an investigational vaccine product for prevention of MERS or SARS;</div>\n<div>\n f. Prior exposure to MERS-CoV or camels (serology or antibody testing will be requested at the Investigator’s discretion);</div>\n<div>\n g. Participants who participated in MERS-201 Part 1 cannot participate in MERS-201</div>\n<div>\n Part 2;</div>\n<div>\n h. Fewer than two acceptable sites available for ID injection and EP considering the deltoid and anterolateral quadriceps muscles. The following are unacceptable sites:</div>\n<div>\n ï‚· Tattoos, keloids or hypertrophic scars located within 2 cm of intended administration site;</div>\n<div>\n ï‚· Implantable-Cardioverter-defibrillator (ICD) or pacemaker (to prevent a lifethreatening arrhythmia) that is located ipsilateral to the deltoid injection site (unless deemed acceptable by a cardiologist);</div>\n<div>\n ï‚· Any metal implants or implantable medical device within the electroporation site;</div>\n<div>\n i. Prisoner or participants who are compulsorily detained (involuntary incarceration);</div>\n<div>\n j. Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids) prior to dosing. Systemic corticosteroids must be discontinued at least 3 months prior to first dose;</div>\n<div>\n k. Reported active drug or alcohol or substance abuse or dependence.</div>\n
      • primary_end_points<div>\n Safety Endpoints:</div>\n<div>\n ï‚· Incidence of adverse events by system organ class (SOC), preferred term (PT), severity and relationship to investigational product</div>\n<div>\n ï‚· Administration (i.e., injection) site reactions (described by frequency and severity)</div>\n<div>\n ï‚· Incidence of adverse events of special interest</div>\n<div>\n  </div>\n<div>\n <div>\n Immunogenicity Endpoints:</div>\n <div>\n ï‚· Overall Immune response</div>\n <div>\n o MERS-CoV antigen specific antibodies</div>\n <div>\n o Antigen-specific cytokine-producing T cell responses</div>\n <div>\n  </div>\n <div>\n <div>\n Exploratory Endpoint:</div>\n <div>\n ï‚· Expanded immunological profile which may include (but not limited to) additional assessment of T and B cell numbers and T and B cell molecular changes by measuring immunologic proteins and mRNA levels of genes of interest at all weeks as determined by sample availability</div>\n </div>\n</div>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImmunogenicity
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specify2a - Vaccine study
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The site specific detauils with regards to capacity of the sites are captured in the respective site specific addendums as follows:</p>\n<p>\n - 4706: MERS SSA version 2_KEN_4706_09 Oct 2020</p>\n<p>\n - 4704: MERS-201_Kericho Site Specific Addendum V1.3 10 Feb 2021</p>\n
      • other_details_explanation<div>\n A Phase 1 clinical trial evaluating GLS-5300 (which is the same product as INO-4700) has been conducted in the United States at Walter Reed Medical Center (clinicaltrials.gov NCT02670187). Additionally, ongoing evaluation in a Phase 1/2a clinical trial is being conducted at two centers in South Korea (clinicaltrials.gov NCT03721718). The Middle East and Africa have been selected to advance MERS-201 in a demographically relevant population.  </div>\n<div>\n  </div>\n
      • other_details_regulatory_notapproved<div>\n Saudi Food and Drug Authority (SFDA)- Submitted 25 Jan 2021</div>\n<div>\n  </div>\n
      • other_details_regulatory_approved<div>\n Jordan Food and Drug Administration (JFDA) - Approval received -16 Feb 2021; 1 site</div>\n<div>\n  </div>\n
      • other_details_regulatory_rejected<p>\n N/A - no rejections </p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationThree years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4 countries
      • number_of_sites2
      • multi_country_listJordan, Lebanon, Saudi Arabia and Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrollment with no maximum - enrollment will stop once target number of subjects is reached
      • total_participants_worldwide542
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationPaediatrician
      • investigator1_professional_addressAhero Clinical Trials Unit c/o CREATES, Strathmore University
      • investigator1_telephone+254733812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants200
      • notification<p>\n Please see below responses to the queries issued by the Kenya Pharmacy and Poisons Board in  response to the submission dated 09Apr2021:</p>\n<ol>\n <li>\n Pg. 6 of the Ahero Clinical Trials Unit-Ahero County Hospital SSA does not mention or include SSA specific information including the expected sample sizes etc. Include SSA-specific information in the Abstract.</li>\n</ol>\n<p style=\"margin-left:54.75pt;\">\n <strong>Response: </strong>This has been added to read: At the ACTU site, a total of 80 participants will be recruited for both part 1 and 2 of the study. Where in part 1 we will recruit 35 participants and part 2, we will recruit 45 participants</p>\n<ol>\n <li value=\"2\">\n For both Kericho and Ahero SSAs, one would have expected to see how the samples of 200 and 80 participants will be treated rather than or in addition to the global samples of 542. This will address the issue of lack of clarity in regards to this matter. e.g. in Kericho SSA Abstract the statement "Kericho site will be enrolling up to 200 participants. Part 1 is a Dose-Finding and approximately 192 participants ages 18-50 years will be assessed through five dose levels and regimens" the first understanding is that 192 participants will be drawn from the 200 participants from the sites. Kindly address this issue.</li>\n</ol>\n<p style=\"margin-left:54.75pt;\">\n <strong>Response: </strong> The enrollment across the different research sites globally will be done competitively. Hence, all sites will enroll into Part 1 until the desired sample size of 192 is achieved, and when the dose is selected for Part 2 (based on Part 1 results through Week 10), the sites will then competitively enroll into Part 2.</p>\n<p style=\"margin-left:54.75pt;\">\n <strong>Site 4704 (Kericho):  </strong> Across these two parts of the study, Kericho site proposes to contribute up to 200 participants<strong>.</strong></p>\n<p style=\"margin-left:54.75pt;\">\n <strong>Site 4706 (ACTU):  </strong>This has been clarified as in 1 above.</p>\n<ol>\n <li value=\"3\">\n The Global Protocol for study does not refer to the four specific sites and investigators from these sites. Kindly clarify the issue and if possible let this protocol capture this very important omission.</li>\n</ol>\n<p style=\"margin-left:54.75pt;\">\n <strong>Response</strong>: As the final site and country list was not available during protocol development, and may change throughout the trial, this information is not included in the protocol document.  However, please find the current planned countries and sites, below:</p>\n<p style=\"margin-left:54.75pt;\">\n Kenya</p>\n<p style=\"margin-left:54.7pt;\">\n       PI: Dr. Josphat Kosgei</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Name: Kenya Medical Research Institute/Walter Reed Project (KEMRI/WRP)</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Address: Off Hospital Road P.O. Box 1357, Kericho, 20200, Kenya</p>\n<p style=\"margin-left:54.7pt;\">\n      </p>\n<p style=\"margin-left:54.7pt;\">\n       PI: Dr. Bernhards Ogutu</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Name: Ahero Clinical Trials Unit</p>\n<p style=\"margin-left:72.0pt;\">\n Site Address: Ahero County Hospital, Ahero Clinical Trials Unit, along Kisumu - Nairobi    Road, Po BOX 54-40100 Kisumu</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:54.75pt;\">\n Lebanon</p>\n<p style=\"margin-left:54.7pt;\">\n       PI: Dr. Ola Mazboudi</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Name: Hammoud Hospital University Medical Center</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Address: Dr. Ghassan Hammoud Street, Saida, Lebanon</p>\n<p style=\"margin-left:54.7pt;\">\n  </p>\n<p style=\"margin-left:54.7pt;\">\n       PI: Dr. Zeina Kanafani</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Name: American University of Beirut Medical Center</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Address: Cairo Street, Hamra, Beirut Lebanon</p>\n<p style=\"margin-left:54.7pt;\">\n  </p>\n<p style=\"margin-left:54.75pt;\">\n Jordan</p>\n<p style=\"margin-left:54.75pt;\">\n       PI: Dr. Suleimman Alsweedan</p>\n<p style=\"margin-left:72.0pt;\">\n Site Name: Pharmaceutical Research Center/Jordan University of  Science and Technology (JUST)</p>\n<p style=\"margin-left:72.0pt;\">\n Site Address: King Abdullah University Hospital, Al Ramtha Street, Irbid 22110, Jordan</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n PI: Dr. Sahem Ghraibeh</p>\n<p style=\"margin-left:72.0pt;\">\n Site Name: Clinical Research Center, Irbid Specialty Hospital (CRC/ISH)</p>\n<p style=\"margin-left:72.0pt;\">\n Site Address: Irbid Specialty Hospital (CRC/ISH), Irbid, princes Hasan street, 21110, Jordan</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n PI: Dr. Lana AlHalaseh</p>\n<p style=\"margin-left:72.0pt;\">\n Site Name: Jordan University Hospital</p>\n<p style=\"margin-left:72.0pt;\">\n Site Address: Queen Rania Al Adbullah Street Amman 11942, Jordan</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:54.75pt;\">\n Kingdom of Saudi Arabia</p>\n<p style=\"margin-left:54.7pt;\">\n       PI: Dr. Mohammed Batais</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Name: King Khaled University Hospital</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Address: Saud University, King Khaled Road, Riyadh, Saudi Arabia</p>\n<p style=\"margin-left:54.7pt;\">\n  </p>\n<p style=\"margin-left:54.7pt;\">\n       PI: Dr. Ziad Memish</p>\n<p style=\"margin-left:54.7pt;\">\n       Site Name: King Saud Medical City</p>\n<p style=\"margin-left:72.0pt;\">\n Site Address: AI Imam Abdul Aziz Ibn Muhammad Ibn Saud, Ulaishah, Riyadh 12746, Saudi Arabia</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<ol>\n <li value=\"4\">\n The sample size in Kenya is given as 200 in the PPB portal application while the Kericho site alone plans to recruit 200 participants and Ahero 80. Also, given that the study will take place in 4 countries, explain why more than 50% of the participants will be drawn from Kenya.</li>\n</ol>\n<p style=\"margin-left:54.75pt;\">\n <strong>Response: </strong>Enrollment in the study is competitive across all sites and the number of particpants per site is an estimate, based on investigator feedback regarding how many participants they expect to enroll within the estimated recruitment period.  The actual number of participants enrolled in each country is not defined up front.</p>\n<ol>\n <li value=\"5\">\n In the midst of the current COVID-19 pandemic, have you considered testing for COVID-19 RNA, antibodies,  or antigens as part of the screening tests and classify the positive results of any of these in the exclusion criteria? Do you think COVID-19 infection, present or past, can affect your results in any way?</li>\n</ol>\n<p style=\"margin-left:54.75pt;\">\n <strong>Response: </strong>The MERS-201 protocol is designed to only enroll healthy volunteers.  Therefore, although no specific eligibility criterion is listed in the protocol to exclude subjects with SARS-CoV2 infection, these subjects will be excluded since they would not meet the basic healthy subject criterion required per protocol.  Since each participating institution and country have developed their own guidelines on how to deal with patients infected with SARS-CoV2, it is difficult to standardize and implement this process within the protocol. </p>\n<p style=\"margin-left:54.75pt;\">\n Another precautionary measure we have implemented in the protocol is to prohibit dosing of subjects suspected of an active infection (i.e., fever within 72 hours).  Any subject experiencing fever within 72 hours should notify the Principal Investigator (PI).  The PI then has the freedom to perform any test/investigation necessary to rule out active infection and follow the institutional mandated COVID-19 protocol, if the subject is confirmed to have the SAR-CoV2 infection.  This process takes place outside the protocol and can only be implemented in symptomatic COVID-19 patients.  Currently, there are no plans to screen for prior exposure to COVID-19.  However, the PI has the discretion to perform any test necessary to declare subject healthy (inclusion criterion “c” of the protocol) prior to enrollment, especially if there a suspicion of COVID-19 exposure or infection. With regard to the immune analysis it is possible that we will see cross reactivity between the antibodies and T cells that react to SARS-CoV2 and MERS.  We have assays developed at Inovio Labs to test for both cellular and humoral responses to SARS-CoV-2.  If a subject demonstrates high antibody or T cells responses at day 0 we will perform our standard SARS-CoV2 immunology assays on the samples.  We will work with data management to analyze these data separately.  Importantly, since we are collecting and assaying at day 0 we will be able to observed a MERS specific response as a response is measured as an increase from day 0.</p>\n<ol>\n <li value=\"6\">\n The Informed Consent Forms for the Kericho and Ahero SSAs appear to be too complicated for participants that are targeted for the study, especially the section on "Clinical Trial Procedures". Consider simplifying the ICF forms for the 2 sites.</li>\n</ol>\n<p style=\"margin-left:58.5pt;\">\n  </p>\n<p style=\"margin-left:58.5pt;\">\n <strong>Response: </strong>The Informed Consent Forms for each site have been revised and are included with this response.</p>\n<p style=\"margin-left:54.0pt;\">\n  </p>\n<ol>\n <li value=\"7\">\n Although it is not a mandatory requirement consider the inclusion of a Kenyan in the DSMB membership</li>\n</ol>\n<p style=\"margin-left:58.5pt;\">\n  </p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Due to the requirement for submission of the final DSMB Charter to several ethics committees and regulatory authorities, the DSMB members were chosen prior to finalizing the site and country list.  At this time, the DSMB membership is fulfilled.  However, if there is ever a need to replace a member of the DSMB, we will consider a participant from Kenya.</li>\n</ul>\n<p>\n  </p>\n<p style=\"margin-left:36.0pt;\">\n We trust this notification fulfils your requirements, however, in the event of any queries, please do not hesitate to contact us.</p>\n<p>\n  </p>\n
      • approval_date15-07-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted10-08-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApplication has been approved by the experts
      • final_report<p>\n INO-4700 is identical to the previously evaluated GLS-5300, except that it is formulated at a higher concentration in a saline sodium citrate (SSC) buffer, rather than in sterile water. The INO-4700 drug product contains 10 mg/mL pGX9101 in 1× SSC buffer (150 mM sodium chloride and 15 mM sodium citrate). In a completed Phase 1 clinical trial, intramuscular (IM) dose ranging administration of GLS-5300 delivered via EP in healthy adults was well-tolerated and induced seroconversion and T cell responses [35] . Transient local injection site discomfort and reactions were most commonly reported, consistent with previously published clinical trial reports of Inovio’s DNA delivered via EP platform. The most common solicited systemic adverse event was headache, followed by malaise and myalgia, most of which were mild. Laboratory abnormalities were uncommon, and no grade 3 or higher laboratory abnormalities were deemed related to the vaccine. No vaccine-related serious adverse events were reported. The vaccine was immunogenic in all dosing groups with remarkably similar antibody and neutralization titers between all three doses. These levels were comparable to those observed in convalescent patients who have recovered from MERS-CoV infection. The vaccine generated long lasting T cell responses that maintained average levels higher than convalescent patients for at least 60 weeks. In summary, the data from this first Phase 1 trial supports the strong immunogenicity of the vaccine and ability to induce durable immune responses for at least 1 year. In an ongoing Phase 1/2a dose-ranging clinical trial, the safety, tolerability and immunogenicity of GLS-5300 delivered ID followed by EP in 60 healthy volunteers was evaluated. Dose levels include 0.3 mg administered in a three immunization regimen at Week 0, 4 and 12, 0.6 mg administered in a three-immunization regimen at Week 0, 4 and 12, and 0.6 mg administered in a twoimmunization regimen at Week 0 and 8. There were no reports of treatment-associated serious adverse events and the majority of adverse events reported were Grade 1 or Grade 2 in severity. The most commonly reported adverse events are similar to that reported in the completed Phase 1 trial. An interim analysis had showed that ID delivery of GLS-5300 induced a robust binding antibody and IFNγ cellular immune response in humans. A dose response was observed, such that the 0.6 mg dose induced significantly higher humoral and cellular immune responses</p>\n<p>\n The 0.6 mg dose induced up to a 76% seroconversion rate following a single immunization, 88% seroconversion following the second immunization, and 100% seroconversion following the third. The 0.6 mg dose also induced robust cellular immune responses, with 56% responders after the second immunization and 78% responders after the third. The two-immunization regimen (Week 0 and 8 dosing) appeared to induce significantly higher antibody titers than the three-immunization regimen (Week 0, 4 12) as early as 2 weeks post second immunization, without affecting the cellular immune response. The overall response rate for the 0.6 mg dose, three-immunization regimen reached 92% after two immunizations and increased to 100% following the third immunization. The 0.6 mg dose, two-immunization regimen reached an overall response rate of 96% after only two immunizations. Results from the complete Phase 1 clinical trial as well as interim safety and immunogenicity results from the ongoing Phase 1/2a clinical trial support continued evaluation of this plasmid in a demographically relevant population. Intradermal delivery has been shown to be a more tolerable route of administration that induces superior humoral immune responses for previously evaluated DNA vaccines targeting viruses such as Ebola, Zika and HIV [37] [38] . As such, Part 1 of the current clinical trial represented the dose-finding phase to supplement previously amassed safety and immunogenicity data. Subjects in Part 1 received dosing on Day 0 and Week 4 or Week 8, with a starting dose of INO-4700 of 0.6 mg, which demonstrated robust immunogenicity in the Phase 1/2a trial of GLS-5300 delivered ID followed by EP</p>\n
      • implication_results<p>\n MERS-201 was a Phase 2a, randomized, blinded, placebo-controlled, multi-center trial to evaluate the safety, tolerability and immunological profile of INO-4700 administered by ID injection followed by EP using the CELLECTRATM 2000 device in healthy adult volunteers. INO-4700, which contains a DNA plasmid encoding the sequence for the MERS-CoV spike protein, was developed as a prophylactic vaccine against MERS-CoV. Immunization with INO-4700 was found to elicit a humoral response. Antibody titers against the against the MERS RBD were noted to increase by Week 6. The highest number of responders were observed in Group E, which included subjects who received 2 mg of INO-4700 + EP at Week 0 and Week 4. Antibody titers against the MERS Spike protein was observed to increase at Week 6 and Week 10. Group E had the highest proportion of spike binding IgG responders at either Week 6 or Week 10, followed by Group B, Group D, Group A, and Group C. Neutralizing antibodies were also shown to increase across INO-4700 + EP study groups. A cellular response was also noted at Week 6. Group E showed the greatest fold increase compared to the other INO4700 groups. MERS-201 Part 1 did not meet the required criteria set by CEPI (70% or higher response rate in one assay at one timepoint) to move forward to Part 2. None of the study groups met the 70% or greater response rate required to proceed to the next phase of the study. INO-4700 was generally safe and well-tolerated when administered ID followed by EP. A total of 37.5% of subjects experienced at least one TEAE; the incidence of TEAEs was similar between the INO-4700 group and the SSC-0001 group. The majority of TEAEs were Grade 1 or Grade 2 in severity. Treatment-related TEAEs were reported in 5.2% of subjects overall. The most common treatment-related TEAE was headache which was reported in 3.1% of the INO-4700 group and in 3.1% of the SSC-0001 group. SAEs were reported in 2 (1.0%) subjects in the INO-4700 group; no treatment-related SAEs were reported. Overall, 3.1% of subjects experienced an AESI. All AESIs were Grade 1 or Grade 2 in severity, nonserious, and assessed to be unrelated to study treatment. There were no TEAEs reported during the trial that led to treatment discontinuation. There were no clinically meaningful changes in vital sign measurements. Only 3 cases of injection site pruritus and 1 case of injection site erythema were observed for injection site reactions. Adverse events were not solicited during the study. We could deduce that INO-4700 with electroporation was well tolerated and can be safely administered as evidenced by the lack of treatment related SAEs as well as low numbers of AEs reported in the clinical trial period which was comparable in both the treatment group and placebo group.</p>\n
      • quantity_imported88
      • quantity_dispensed41
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      • final_date0000-00-00
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        • given_nameBernhards
        • middle_name
        • family_nameOgutu
        • qualificationPaediatrics
        • professional_addressAhero Clinical Trials Unit c/o CREATES, Strathmore University
        • telephone+254733812613
        • emailogutu6@gmail.com
        • created2020-12-15 09:30:15
        • modified2021-08-10 15:42:47
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        • given_nameJosphat
        • middle_name
        • family_nameKosgei
        • qualificationClinical Research
        • professional_addressKEMRI/WRP, Kericho
        • telephone+254729110122
        • emailjosphat.kosgei@usamru-k.org
        • created2021-04-19 15:58:20
        • modified2021-08-10 15:42:47
    • SiteDetail(array)
      • 0(array)
        • id841
        • application_id963
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        • site_nameAhero Clinical Trials Unit
        • physical_addressAhero County Hospital ,Ahero Clinical Trials Unit , along Kisumu -Nairobi Road
        • contact_detailsP.O. BOX 54-40100
        • contact_personBernhards Ogutu
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          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
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        • site_nameKenya Medical Research Institute/Walter Reed Project (KEMRI/WRP)
        • physical_addressKenya Medical Research Institute/Walter Reed Project (KEMRI/WRP), Off Hospital Road
        • contact_detailsP.O. Box 1357 KERICHO. 20200. KENYA. Tel (+254-(0)5220) 36000/36100 Fax (+254-(0)5220) 30546/30662
        • contact_personJosphat Kosgei
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        • id472
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        • sponsorInovio Pharmaceuticals Inc.
        • sponsor_typeIndustry
        • contact_personBonaventure Orizu, MD
        • address660 West Germantown Pike, Suite 110 Plymouth Meeting, PA 19462, USA
        • telephone_number+1858-410-3328
        • fax_number
        • cell_number+1267-589-9474
        • email_addressBon.Orizu@inovio.com
        • created2020-12-15 09:30:15
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      • abstract_of_study<div>\n TITLE: Single-use antimalarial monoclonal antibodies for post-discharge malaria prevention in</div>\n<div>\n children with severe anaemia or severe malaria in Kenya: A multi-centre, parallel-group, two-arm</div>\n<div>\n randomised placebo-controlled non-inferiority trial (L9LS-pd).</div>\n<div>\n BACKGROUND AND RATIONALE: Hospitalised children with severe anaemia remain at high risk of</div>\n<div>\n dying or requiring hospital readmission for at least 6 months after discharge. In highly malariaendemic</div>\n<div>\n settings, malaria is a major contributor to these post-discharge readmissions and deaths. In</div>\n<div>\n 2022, the World Health Organisation (WHO) recommended post-discharge malaria</div>\n<div>\n chemoprevention (PDMC) for children hospitalised with severe anaemia living in malarious areas.</div>\n<div>\n Kenya, together with several other countries in sub-Saharan Africa, aims to expand WHO’s</div>\n<div>\n recommendation and introduce PDMC in children hospitalised with severe anaemia or severe</div>\n<div>\n malaria, including children with severe malaria who do not have severe anaemia (e.g. cerebral</div>\n<div>\n malaria). PDMC consists of full 3-day treatment courses with long-acting antimalarials given monthly</div>\n<div>\n three times after discharge. PDMC is very effective in clinical trials. However, adherence to these</div>\n<div>\n monthly 3-day drug treatments is limited under real-life conditions. Furthermore, PDMC provides</div>\n<div>\n chemoprevention for about 3.5 months only, while the risk of dying or needing to be readmitted</div>\n<div>\n remains high for several more months.</div>\n<div>\n The US National Institutes of Health (NIH) has developed two monoclonal antibodies targeting</div>\n<div>\n Plasmodium falciparum malaria (mMAb). These proteins specifically target a highly conserved</div>\n<div>\n epitope found on the circumsporozoite protein-1 (CSP-1) of P. falciparum to neutralize it and</div>\n<div>\n prevent malaria infection. A key feature of mMAbs is that they can provide protection for up to 6</div>\n<div>\n months with a single dose and thus serve as a “long-acting” drug. Recent placebo-controlled studies</div>\n<div>\n in healthy adults in Mali suggest that the first mMAb, CIS43LS, when administered at a dose of 40</div>\n<div>\n mg/kg intravenously (IV), can block 88% of malaria infections for at least 6 months. More recently,</div>\n<div>\n studies with a newer mMAb called L9LS, which is anticipated to be more potent than CIS43LS,</div>\n<div>\n showed a 74% reduction in uncomplicated clinical malaria by 6 months when administered</div>\n<div>\n subcutaneously to healthy Malian children aged 6-10 years by a single subcutaneous (SC) dose of 10-</div>\n<div>\n 20 mg/kg (NCT05304611). Similar studies with L9LS are ongoing in healthy children under 5 years of</div>\n<div>\n age in Siaya, western Kenya (NCT05400655).</div>\n<div>\n Young children admitted to hospitals in highly malaria-endemic areas with severe anaemia or severe</div>\n<div>\n malaria are an ideal target group for passive immunoprevention with mMAbs as a single infusion</div>\n<div>\n with mMAb while in the hospital could protect this high-risk group during the entire vulnerable postdischarge</div>\n<div>\n period.</div>\n<div>\n OVERVIEW DESIGN: We will conduct a 2-arm, multi-centre, individually randomised, placebocontrolled</div>\n<div>\n non-inferiority trial in 398 children with severe malaria or severe anaemia. Children will</div>\n<div>\n be randomly assigned (1:1) using an adaptive minimisation algorithm to receive either mMAb before</div>\n<div>\n discharge or 3 courses of monthly PDMC after discharge, according to WHO guidelines. The study</div>\n<div>\n will be placebo-controlled. Children in the PDMC arm will receive a placebo infusion with normal</div>\n<div>\n saline before discharge; children in the mMAb arm will receive placebo-PDMC. All children will</div>\n<div>\n receive standard in-hospital care, including a blood transfusion and treatment for severe malaria</div>\n<div>\n where indicated. They will also receive a full 3-day treatment course with the antimalarial</div>\n<div>\n artemether-lumefantrine (AL) to clear any existing malaria infections as soon as they have recovered</div>\n<div>\n and can take oral medication.</div>\n<div>\n The primary endpoint is the incidence of clinical malaria detected by passive case detection by 6</div>\n<div>\n months post-discharge (the intervention period). Key secondary endpoints include the rates of readmissions and deaths (all children). Children will be followed for another 6 months (postintervention</div>\n<div>\n period) to determine the duration of protection, any long-term impact (e.g., growth)</div>\n<div>\n and if mMAbs result in a delayed acquisition of natural protective immunity against clinical malaria.</div>\n<div>\n PRIMARY EFFICACY OBJECTIVE: To assess the efficacy of a single dose of L9LS versus PDMC against</div>\n<div>\n microscopy or RDT-confirmed clinical malaria in hospitalised children with severe anaemia or severe</div>\n<div>\n malaria by 6 months after investigational product (IP) administration.</div>\n<div>\n SITES: Two hospitals in western Kenya in areas with moderate to intense malaria transmission. The</div>\n<div>\n number of hospitals will be expanded if recruitment rates require this.</div>\n<div>\n STUDY POPULATION: Inclusion criteria: convalescent children aged less than 10 years and weighing</div>\n<div>\n ≥5 kg hospitalised with severe anaemia (haemoglobin<5g/dL / Ht<15%) or severe malaria who have</div>\n<div>\n become clinically stable and can take or switch to oral medication; post-transfusion Hb >5g/dL,</div>\n<div>\n resident in the study area, provision of informed consent by parents or guardian. Exclusion criteria:</div>\n<div>\n Children eligible for any of the four doses of the RTS,S or R21 malaria vaccines, HIV-infected or HIVexposed</div>\n<div>\n children on daily cotrimoxazole prophylaxis, blood loss due to trauma, malignancy, known</div>\n<div>\n bleeding disorders, known hypersensitivity to study drug, known heart conditions or family history</div>\n<div>\n of congenital QT prolongation, or taking medicinal products that are known to prolong the QTc</div>\n<div>\n interval, non-resident in the study area, previous participation in the study, known need at</div>\n<div>\n enrolment for prohibited medication and scheduled surgery during the 12-month course of the</div>\n<div>\n study.</div>\n<div>\n STUDY INTERVENTIONS: All children will receive standard in-hospital care, including a blood</div>\n<div>\n transfusion, antibiotics, and treatment for severe malaria where indicated. All children in both arms</div>\n<div>\n will be empirically treated for malaria infection around discharge with a 3-day regimen with</div>\n<div>\n artemether-lumefantrine to ensure parasite clearance of any existing parasites. Participants in the</div>\n<div>\n mMAb arm will receive the study agent L9LS IV with a target dose of 30 mg/kg. The IV dose will use 1</div>\n<div>\n kg step increases. During the 6-month intervention period, children in the placebo-mMAbs arm will</div>\n<div>\n receive three courses of monthly PDMC as per WHO guidelines with dihydroartemisinin-piperaquine</div>\n<div>\n (DP) at 2, 6 and 10 weeks post-discharge. Those in the mMAbs arm will receive an identical placebo</div>\n<div>\n PDMC. (Table 1, below).</div>\n<div>\n Table 1: Study arms</div>\n<div>\n Study arm</div>\n<div>\n mMAb (L9LS) + placebo-PDMC Placebo-mMAb + PDMC</div>\n<div>\n ï‚· Infusion with the mMAb L9LS before</div>\n<div>\n discharge</div>\n<div>\n ï‚· Placebo-PDMC at the end of weeks 2, 6,</div>\n<div>\n 10 post-discharge</div>\n<div>\n ï‚· Placebo-infusion with normal saline before</div>\n<div>\n discharge</div>\n<div>\n ï‚· PDMC with DP at the end of weeks 2, 6, 10</div>\n<div>\n post-discharge</div>\n<div>\n mMAb=Antimalarial monoclonal Antibody (L9LS). PDMC=post-discharge malaria chemoprevention</div>\n<div>\n DP=dihydroartemisinin-piperaquine.</div>\n<div>\n FOLLOW-UP PROCEDURES: Children will be followed for 12 months by passive surveillance</div>\n<div>\n (unscheduled sick visits) in 2 phases: a 6-month intervention period to the end of month 6 postdischarge</div>\n<div>\n (day 183 inclusive); a 6-month post-intervention period from month 7 to 12 inclusive (day</div>\n<div>\n 184 to +1 year minus 1 day following discharge).</div>\n<div>\n OUTCOME MEASURES: Primary: Incidence rate of clinical malaria from 3 to 26 weeks post-discharge,</div>\n<div>\n defined as an illness accompanied by measured fever ≥37.5°C or a history of fever (subjective or</div>\n<div>\n objective) in the previous 24 hours, accompanied by any level of asexual parasitaemia detected by</div>\n<div>\n microscopy or RDT (pLDH or HRP2-band). The HRP2-band results will only be considered when</div>\n<div>\n microscopy or the RDT pLDH band results are unavailable. Key secondary outcomes include the</div>\n<div>\n following outcomes measured during the follow-up periods (intervention and post-intervention): Allcause</div>\n<div>\n and cause-specific readmissions, all-cause non-severe sick-child clinic visits and those</div>\n<div>\n unrelated to malaria, and the pharmacokinetic parameters of L9LS. Other secondary efficacy</div>\n<div>\n outcomes include those measured during cross-sectional surveys conducted at the end of the</div>\n<div>\n intervention and post-intervention periods, including the prevalence of malaria infection, clinical</div>\n<div>\n malaria, anaemia, and standard anthropometric measures of malnutrition. Exploratory endpoints</div>\n<div>\n include immunological endpoints. Safety endpoints include solicited and unsolicited AEs (local and</div>\n<div>\n systemic) following mMAb administration and anti-drug antibodies (ADA) at 6 and 12 months.</div>\n<div>\n SAMPLE SIZE: This will be a parallel, 2-arm, placebo-controlled, non-inferiority trial using a 1:1</div>\n<div>\n allocation ratio. In this non-inferiority trial, we compare mMAbs against monthly PDMC, assuming</div>\n<div>\n higher incidence rates are worse. The primary endpoint is clinical malaria during 24 weeks between</div>\n<div>\n 3 and 26 weeks post-discharge. The non-inferiority ratio is 1.1. To demonstrate non-inferiority with</div>\n<div>\n 90% power and a one-sided significance level of 0.025 and assuming a potential reduction by</div>\n<div>\n mMAbs relative to PDMC of 54% (IRR=0.456) from 72 to 33 per 100 person-years, the study requires</div>\n<div>\n approximately 398 participants (199 per arm), considering a 15% dropout rate and an overdispersion</div>\n<div>\n parameter of 1.18. The trial includes two interim analyses for efficacy and sample size re-estimation</div>\n<div>\n when 50% and 75% of participants have completed their 6-month follow-up.</div>\n<div>\n DATA ANALYSIS: The primary analysis will use the modified intention-to-treat population, including</div>\n<div>\n all randomised participants contributing to the outcome. Incidence rates will be calculated, and</div>\n<div>\n incidence rate ratios will be estimated using negative binomial regression by treatment as</div>\n<div>\n randomised. The analysis time will be divided into a) the intervention period (first 6 months, primary</div>\n<div>\n analysis), b) the post-intervention period (6-12 months), c) and the cumulative effect by 12 months.</div>\n<div>\n If non-inferiority is demonstrated, an analysis for superiority will be conducted.</div>\n<div>\n IMPACT: The potential application of mMAb would be routine administration to hospitalised</div>\n<div>\n children with severe anaemia or severe malaria in highly malarious areas. The potential benefits</div>\n<div>\n include the prevention of post-discharge deaths, readmissions, and malaria episodes in these</div>\n<div>\n vulnerable groups of children.</div>\n<div>\n PARTNERS INSTITUTIONS: KEMRI, NIAID-NIH, LSTM, US-CDC</div>\n<div>\n FUNDING: NIH and CDC</div>\n<div>\n SPONSOR: LSTM</div>\n
      • study_title<div>\n Single-use antimalarial monoclonal antibodies for post-discharge malaria prevention in children with severe anaemia or severe malaria in Kenya: A multi-centre, parallel-group, two-arm randomised placebo-controlled non-inferiority trial (L9LS-pd)</div>\n
      • laymans_summary<div>\n Hospitalised children with severe anaemia or severe malaria remain at high risk of dying or requiring</div>\n<div>\n readmission after discharge for at least 6 months. In highly malaria-endemic settings, malaria is a</div>\n<div>\n major contributor. In 2022, the World Health Organisation (WHO) recommended post-discharge</div>\n<div>\n malaria prevention (PDMC) for children hospitalised with severe anaemia living in malarious areas.</div>\n<div>\n Kenya and several other countries in sub-Saharan Africa aim to expand WHO’s PDMC</div>\n<div>\n recommendation to children hospitalised with severe anaemia or severe malaria. PDMC consists of</div>\n<div>\n full 3-day treatment courses with long-acting antimalarials given monthly, three times after hospital</div>\n<div>\n discharge, providing about 14 weeks of protection. PDMC is very effective in clinical trials. However,</div>\n<div>\n previous studies showed that adherence to the monthly 3-day treatment course is limited under</div>\n<div>\n real-life conditions. Furthermore, PDMC only provides protection for 3.5 months, while the excess</div>\n<div>\n risk of dying or needing to be readmitted remains high for the first 6 months after discharge.</div>\n<div>\n The US National Institutes of Health (NIH) has developed a new intervention against malaria called</div>\n<div>\n an antimalarial monoclonal antibody (mMAb). These are laboratory-made versions of a naturally</div>\n<div>\n produced antibody specifically targeting the malaria parasite to neutralize and prevent infection. A</div>\n<div>\n key feature of mMAbs is that they can provide protection for up to 6 months with a single dose and</div>\n<div>\n thus serve as a “long-acting” drug. The first mMAb, CIS43LS, provided 88% protection against</div>\n<div>\n malaria infection for at least 6 months when given intravenously (IV) by infusion in healthy adults in</div>\n<div>\n Mali, West Africa. More recently, studies with a newer mMAb called L9LS showed a 74% reduction in</div>\n<div>\n malaria disease by 6 months when given by injection under the skin (subcutaneously [SC]) to healthy</div>\n<div>\n Malian children aged 6-10 years. Similar studies with L9LS are ongoing in healthy children under 5</div>\n<div>\n years of age in Siaya, western Kenya. All studies so far have demonstrated that mMAbs are safe and</div>\n<div>\n well tolerated. Hospitalised children with severe anaemia or severe malaria are an ideal target group</div>\n<div>\n for protection against malaria by mMAb in highly malaria-endemic areas because a single infusion</div>\n<div>\n with a mMAb, while still admitted in the hospital, could potentially protect them during the entire</div>\n<div>\n vulnerable 6-month post-discharge period. Furthermore, unlike malaria vaccines, which require</div>\n<div>\n three doses to provide protection, mMAbs provide immediate protection and don’t require the</div>\n<div>\n children to mount their own immune response, which can be variable.</div>\n<div>\n We propose a trial in 398 children hospitalised with severe anaemia or severe malaria in high</div>\n<div>\n malaria transmission areas in western Kenya. We will compare the efficacy and safety of an infusion</div>\n<div>\n with the mMAb L9LS provided before discharge to the standard-of-care with PDMC recommended</div>\n<div>\n by WHO. PDMC will comprise three 3-day treatment courses provided at 2, 6 and 10 weeks postdischarge</div>\n<div>\n with the long-acting antimalarial dihydroartemisinin-piperaquine (DP), the most effective</div>\n<div>\n antimalarial used in all previous PDMC trials. The study will be placebo-controlled. Children in the</div>\n<div>\n PDMC arm will receive a placebo infusion with normal saline before discharge; children in the</div>\n<div>\n mMAbs arm will receive placebo-PDMC with placebo tablets that look identical to the real DP. All</div>\n<div>\n children will receive standard in-hospital care, including a blood transfusion and treatment for</div>\n<div>\n severe malaria where indicated. They will also receive a full 3-day treatment course with the</div>\n<div>\n antimalarial artemether-lumefantrine (AL) to clear any existing malaria infections as soon as they</div>\n<div>\n have recovered and can take oral medication.</div>\n<div>\n Children will be followed for 1 year. We will compare the rates of clinical malaria between the</div>\n<div>\n mMAb and the PDMC arms by 6 months post-discharge (the end of the ‘intervention period’)</div>\n<div>\n (primary endpoint). We will also compare the rates of hospital readmissions and deaths. We will</div>\n<div>\n then follow them for another 6 months (post-intervention period) to determine the longevity of the</div>\n<div>\n protective effect and any longer-term benefits (e.g., on growth) or whether protection in the first 6</div>\n<div>\n months results in delayed malaria, e.g. due to delayed acquisition of natural protective immunity</div>\n<div>\n against malaria.</div>\n<div>\n Written informed consent will be obtained from caregivers. The potential application of mMAb</div>\n<div>\n would be routine administration to hospitalised children with severe anaemia or severe malaria in</div>\n<div>\n highly malarious areas.</div>\n
      • short_titleL9LS-PD
      • protocol_noECCT/24/09/01
      • version_no1.2
      • date_of_protocol31-07-2024
      • study_drugL9LS
      • disease_conditionMalaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_name0.9% Normal Saline
      • comparator_registeredYes
      • comparator_countriesGlobal
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressRNjoroge@kemri.go.ke
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
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      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
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      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
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      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
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      • statistical_analysis_plan1
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      • declaration_applicantRuth Njoroge
      • declaration_date116-09-2024
      • declaration_principal_investigatorSimon Kariuki
      • declaration_date216-09-2024
      • placebo_presentYes
      • study_objectives<div>\n To assess the efficacy of a single dose of</div>\n<div>\n <div>\n L9LS versus PDMC against microscopy or</div>\n <div>\n RDT-confirmed clinical malaria in</div>\n <div>\n hospitalised children with severe</div>\n <div>\n anaemia or severe malaria by 6 months</div>\n <div>\n after investigational product (IP)</div>\n <div>\n administration</div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n ï‚· Aged <10 years of both sexes</div>\n<div>\n ï‚· Severe anaemia or severe malaria: Initially hospitalised with haemoglobin <5.0 g/dl</div>\n<div>\n or PCV <15%, or requirement for blood transfusion for other clinical reasons on or</div>\n<div>\n during admission to the hospital, or severe malaria, defined as a requirement for</div>\n<div>\n parenteral artesunate in the opinion of the treating clinician and the presence of</div>\n<div>\n microscopy or RDT confirmed Plasmodium infection</div>\n<div>\n ï‚· Resident in catchment area</div>\n<div>\n ï‚· Post-transfusion haemoglobin >=5.0 g/dl or PCV >=15%</div>\n<div>\n ï‚· Clinically stable, able to take oral medication, able to feed (for breastfeeding</div>\n<div>\n children) or eat (for older children) and able to sit unaided (for older children who</div>\n<div>\n were already able to do so before hospitalisation)</div>\n<div>\n ï‚· Provision of informed consent by parent or guardian</div>\n
      • principal_exclusion_criteria<div>\n ï‚· Recognised specific other causes of severe anaemia (i.e., trauma, haematological</div>\n<div>\n malignancy, known bleeding disorders, such as haemophilia)</div>\n<div>\n ï‚· Sickle cell anaemia/sickle cell disease</div>\n<div>\n ï‚· Body weight <5 kg</div>\n<div>\n ï‚· Fever (≥37.5oC) on the day of enrolment is not an exclusion criterion as long as the</div>\n<div>\n child is considered clinically stable.</div>\n<div>\n ï‚· HIV infection or on daily cotrimoxazole prophylaxis.</div>\n<div>\n ï‚· Previous enrolment in the present study</div>\n<div>\n ï‚· Children who are scheduled to receive any of the four doses of the malaria vaccine</div>\n<div>\n within 6 months after enrolment.</div>\n<div>\n ï‚· Received any RTS,S or R21 malaria vaccine primary series or booster dose within</div>\n<div>\n the last 14 days inclusive</div>\n<div>\n ï‚· On or eligible for cotrimoxazole prophylaxis for HIV infection or HIV exposure</div>\n<div>\n ï‚· Children with sickle cell disease because they are eligible for daily proguanil</div>\n<div>\n ï‚· Known hypersensitivity to artemether-lumefantrine or dihydroartemisininpiperaquine</div>\n<div>\n ï‚· Anticipated to reside for more than 1 month of the 6-month (26 weeks)</div>\n<div>\n intervention period outside of the catchment area (e.g. boarding school)</div>\n<div>\n ï‚· Use or known need at enrolment for concomitant prohibited medication during the</div>\n<div>\n first 6 months post-discharge</div>\n<div>\n ï‚· Ongoing or planned participation in another clinical trial involving ongoing or</div>\n<div>\n scheduled treatment with prohibited medicinal products or active follow-up during</div>\n<div>\n the first 26 weeks post-discharge</div>\n<div>\n ï‚· A known need at the time of enrolment for scheduled surgery during the first 6</div>\n<div>\n months post-discharge</div>\n<div>\n ï‚· Suspected non-compliance with the follow-up schedule and protocol in the opinion</div>\n<div>\n of the investigator</div>\n<div>\n ï‚· Known heart conditions or family history of congenital prolongation of the QTc</div>\n<div>\n interval, or taking medicinal products that are known to prolong the QTc interval</div>\n
      • primary_end_points<div>\n Incidence rate of clinical malaria from 3 to 26</div>\n<div>\n weeks post-discharge, defined as an illness</div>\n<div>\n accompanied by measured fever ≥37.5°C or a</div>\n<div>\n history of fever (subjective or objective) in the</div>\n<div>\n previous 24 hours, accompanied by any level of</div>\n<div>\n asexual parasitaemia detected by microscopy or</div>\n<div>\n RDT (pLDH or HRP2-band). The HRP2-band results</div>\n<div>\n will only be considered when microscopy or the</div>\n<div>\n RDT pLDH band results are unavailable.</div>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
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      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n <u><strong>Homa Bay County Teaching and Referral Hospital</strong></u></div>\n<div>\n <u><strong>Clinical Trial Site Profile</strong></u></div>\n<div>\n 1. Facility Overview</div>\n<div>\n Homa Bay County Teaching and Referral Hospital is a 300-bed government healthcare facility in Homa Bay County, Kenya. As a teaching and referral hospital, it serves as an ideal location for conducting clinical trials, combining advanced medical care with research capabilities.</div>\n<div>\n 2. Location and Demographics</div>\n<div>\n • Situated approximately 110 kilometers (2-hour drive) from Kisumu</div>\n<div>\n •Located in an area of intense malaria transmission, providing access to a relevant patient population for tropical disease studies</div>\n<div>\n • Serves a diverse population, facilitating recruitment</div>\n<div>\n 3. Clinical Trial Infrastructure</div>\n<div>\n 3.1 Dedicated Clinical Trial Facility</div>\n<div>\n •Two well equipped laboratories dedicated for assessment of safety and analyses of laboratory parameters</div>\n<div>\n •</div>\n<div>\n GCP-compliant site pharmacy with secure storage and temperature monitoring systems</div>\n<div>\n •</div>\n<div>\n Multiple clinical rooms for participant care and study specific procedures</div>\n<div>\n •</div>\n<div>\n Secure data management room with backup power supply</div>\n<div>\n 3.2 Sample Processing and Storage</div>\n<div>\n •Capability for on-site sample processing, including centrifugation and aliquoting</div>\n<div>\n •-80°C freezers and liquid nitrogen storage for long-term sample preservation</div>\n<div>\n •Temperature-monitored sample storage</div>\n<div>\n 3.3 Pharmacy</div>\n<div>\n •Controlled access to investigational products</div>\n<div>\n •Temperature-controlled storage for drugs and vaccines</div>\n<div>\n •Capability for drug reconstitution and preparation on site</div>\n<div>\n 4. Research Team and Expertise</div>\n<div>\n •Multidisciplinary team includes:</div>\n<div>\n •Principal Investigator with extensive clinical trial experience</div>\n<div>\n •Sub-investigators and dedicated medical officers</div>\n<div>\n •GCP-trained research nurses and clinicians</div>\n<div>\n •Certified clinical research coordinators</div>\n<div>\n •Experienced laboratory technologists</div>\n<div>\n •Qualified pharmacist and pharmaceutical technologists</div>\n<div>\n •Trained data clerks for accurate data entry and management</div>\n<div>\n •Field workers for community engagement and participant follow-up</div>\n<div>\n 5. Quality Assurance and Regulatory Compliance</div>\n<div>\n •Regular internal audits and readiness for sponsor audits and regulatory inspections</div>\n<div>\n •Compliance with ICH-GCP guidelines and local regulatory requirements</div>\n<div>\n •Standardized Operating Procedures (SOPs) for all clinical trial processes</div>\n<div>\n 6. Data Management and Safety</div>\n<div>\n •Electronic Data Capture (EDC) system with secure, backed-up servers</div>\n<div>\n •Strict data privacy and protection measures in compliance with clinical trial requirements</div>\n<div>\n •Real-time data entry and regular data cleaning processes</div>\n<div>\n •Dedicated safety reporting system for Adverse Events (AEs) and Serious Adverse Events (SAEs)</div>\n<div>\n 7. Community Engagement and Participant Recruitment</div>\n<div>\n •Strong ties with the local community, facilitating recruitment and retention</div>\n<div>\n •Experienced community advisory board to ensure culturally appropriate engagement</div>\n<div>\n •Capability to conduct community awareness programs about clinical research</div>\n<div>\n 8. Collaborative Network</div>\n<div>\n Established partnerships with regional healthcare facilities for:</div>\n<div>\n •Extended participant recruitment</div>\n<div>\n •Long-term follow-up capabilities</div>\n<div>\n •Referral system for specialized care if required during trials</div>\n<div>\n Some collaborating facilities:</div>\n<div>\n 1. Kendu Bay Hospital</div>\n<div>\n 2. Rachuonyo Sub-County Hospital</div>\n<div>\n 3. Nyamira County Referral Hospital</div>\n<div>\n  </div>\n<div>\n 9. Clinical Trial Experience</div>\n<div>\n The Homa Bay County Teaching and Referral Hospital has a strong track record in as a site for clinical trials, particularly in areas relevant to the local disease burden. The experience includes, but is not limited to:</div>\n<div>\n •Post-Discharge Malaria Chemoprevention Trial: A recent study investigating the efficacy of Dihydroartemisinin-piperaquine for preventing malaria in children after hospital discharge. This trial demonstrates our capability to conduct complex, multi-phase studies involving follow-up care.</div>\n<div>\n •Malaria in Pregnancy Trials: Multiple studies focusing on the prevention and treatment of malaria in pregnant women, addressing a critical health concern in the region. Pregnancy registry platform</div>\n<div>\n •Other phase 2 and 3 clinical trials in paediatrics</div>\n<div>\n This diverse number of clinical trials showcases the site’s ability to:</div>\n<div>\n •Recruit and retain participants from various demographic groups</div>\n<div>\n •Implement complex study protocols</div>\n<div>\n •Manage and analyze large datasets</div>\n<div>\n •Collaborate with international research partners</div>\n<div>\n •Adhere to rigorous ethical and regulatory standards</div>\n<div>\n 10. Training</div>\n<div>\n •Regular GCP and research ethics training for all staff involved in clinical trials</div>\n<div>\n •Ongoing professional development programs for research team members</div>\n<div>\n •Collaboration with international research institutions for knowledge exchange</div>\n<div>\n  </div>\n<div>\n <div>\n <u><strong>Siaya County Referral Hospital</strong></u></div>\n <div>\n <u><strong>Clinical Trial Site Profile</strong></u></div>\n <div>\n 1. Facility Overview</div>\n <div>\n Siaya County Referral Hospital is a 260-bed public healthcare facility located in Siaya Town, Siaya County, western Kenya. As the main public hospital in the County, it serves primarily a rural population and plays a crucial role in healthcare delivery and medical research in the region</div>\n <div>\n 2. Location and Demographics</div>\n <div>\n •Situated in Siaya Town, Siaya County, western Kenya</div>\n <div>\n •Located in an area of high perennial malaria transmission in the lake region</div>\n <div>\n •Serves mainly a rural population, providing access to a relevant demographic for various clinical studies</div>\n <div>\n 3. Hospital Capacity and Specialties</div>\n <div>\n •Total capacity: 260 beds</div>\n <div>\n •General wards: 200 beds</div>\n <div>\n •Dedicated pediatric unit: 60 beds</div>\n <div>\n •Specializes in providing care for malaria and other prevalent conditions in the region</div>\n <div>\n 4. Research Infrastructure and Expertise</div>\n <div>\n It hosts a dedicated Clinical Research Centre (CRC), with over two decades of clinical trial experience. The CRC is equipped to handle various types of clinical studies, from early-phase trials to large-scale efficacy studies.</div>\n <div>\n It has experienced research staff familiar with Good Clinical Practice (GCP) and international research standards.</div>\n <div>\n The Siaya site also hosts the KEMRI/CDC Health and Demographic Surveillance System (HDSS) a crucial research infrastructure that provides extensive data and support for various studies. It Provides longitudinal population-based demographic information and data on disease burden, particularly focusing on common causes of morbidity and mortality in Kenya and East Africa.</div>\n <div>\n 5. Extensive Clinical Trial Experience</div>\n <div>\n The Siaya site has a rich history of conducting significant clinical trials, including but not limited to:</div>\n <div>\n Malaria Vaccine Trials: Participation in pivotal studies that have contributed to the development and testing of malaria vaccines, positioning the site at the forefront of malaria prevention research.</div>\n <div>\n Monoclonal Antibody (MmAB) Trials: Experience in conducting trials with advanced biologic therapies, including monoclonal antibodies, demonstrating capability in handling complex investigational products.</div>\n <div>\n Ongoing Studies with MmAB L9LS: Since 2022, the hospital has been conducting studies with MmAB L9LS in healthy children, showcasing their current involvement in cutting-edge malaria prevention research.</div>\n <div>\n Various other trials related to tropical diseases, paediatric health, and public health interventions relevant to the local population</div>\n <div>\n This extensive and diverse clinical trial experience highlights the site's ability to:</div>\n <div>\n •Implement complex study protocols</div>\n <div>\n •Manage a wide range of investigational products</div>\n <div>\n •Recruit and retain participants from various demographic groups</div>\n <div>\n •Collaborate effectively with international sponsors and research organizations</div>\n <div>\n •Contribute significantly to the advancement of medical knowledge, particularly in the fields of malaria and tropical diseases</div>\n <div>\n 6. Collaborative Network</div>\n <div>\n Siaya CRC collaborates closely with other healthcare facilities in the region to enhance patient care, research, and medical education. Some collaborating facilities include:</div>\n <div>\n 1. Bondo Sub-County Referral Hospital</div>\n <div>\n 2. Madiany Sub-County Hospital</div>\n <div>\n 3. Uyawi Sub-County Hospital</div>\n <div>\n 4. Other hospitals and lower-level health facilities in Kisumu and neighboring Counties</div>\n <div>\n These partnerships facilitate:</div>\n <div>\n •Patient enrollment in medical studies</div>\n <div>\n •Follow-up care for trial participants</div>\n <div>\n •Comprehensive healthcare coverage for the region</div>\n <div>\n •Extended reach for clinical trials and research initiatives</div>\n <div>\n 7. Malaria Research Focus</div>\n <div>\n •The hospital's location in an area of high perennial malaria transmission makes it an ideal site for malaria-related studies</div>\n <div>\n •Experience with malaria studies in paediatric populations</div>\n <div>\n •Potential for year-round recruitment of malaria cases for clinical trials</div>\n <div>\n 8. Paediatric Expertise</div>\n <div>\n •Dedicated 60-bed paediatric unit</div>\n <div>\n •Experience in conducting paediatric clinical trials, as evidenced by the ongoing MmAB L9LS studies with dedicated paediatrician-scientists.</div>\n <div>\n •Capability to manage complex paediatric cases, which is crucial for child-focused clinical trials</div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n LSTM</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration> 3 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparator0.9% normal saline
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site398
      • total_participants_worldwide398
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyChildren aged below 10 years
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFeiko
      • investigator1_middle_name
      • investigator1_family_nameter Kuile
      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressLiverpool School of Tropical Medicine (LSTM) Pembroke Place, L3 5QA Liverpool, United Kingdom and 1578 - 40100 KEMRI-CGHR Kisumu, Kenya.
      • investigator1_telephone+254 708 739 228
      • investigator1_emailFeiko.terkuile@lstmed.ac.uk
      • organisations_transferred_No
      • number_participants398
      • notification
      • approval_date16-03-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted16-09-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted16-09-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonSatisfactory feedback was provided upon ECCT review, with the pending response on MTA and QP declaration
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-03-26 12:56:13
      • created2024-08-12 11:33:06
      • total_sites2
      • ecitizen_invoice(null)
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        • id1160
        • application_id1458
        • given_nameMary
        • middle_nameIwaret
        • family_nameOtiti
        • qualificationMD
        • professional_address1578 - 40100 KEMRI-CGHR Kisumu, Kenya
        • telephone0724007076
        • emailiwaret.otiti@lstmed.ac.uk
        • created2024-09-11 06:13:40
        • modified2025-01-15 17:49:31
    • SiteDetail(array)
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        • id1787
        • application_id1458
        • county_id43
        • site_nameHoma Bay County Teaching and Referral Hospital
        • physical_addressHoma Bay Town
        • contact_details+254724007076
        • contact_personDr. Mary Iwaret Otiti
        • site_capacity(null)
        • misc(null)
        • created2024-09-11 06:13:40
        • modified2025-01-15 17:49:31
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          • county_nameHoma Bay
          • created2012-06-15 10:27:10
          • modified2012-06-15 10:27:10
      • 1(array)
        • id1788
        • application_id1458
        • county_id41
        • site_nameSiaya County Referral Hospital
        • physical_addressSiaya Town
        • contact_details+254724007076
        • contact_personDr. Mary Iwaret Otiti
        • site_capacity(null)
        • misc(null)
        • created2024-09-11 06:58:58
        • modified2025-01-15 17:49:31
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id782
        • application_id1458
        • sponsorLiverpool School of Tropical Medicine (LSTM)
        • sponsor_typeResearch Institution
        • contact_person
        • addressPembroke Place, Liverpool L3 5QA, UK
        • telephone_number+44 0151 7053794
        • fax_number
        • cell_number+44 0151 7053794
        • email_addresslstmgov@lstmed.ac.uk
        • created2024-09-11 06:13:40
        • modified2025-01-15 17:49:31
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    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php