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• applications(array)
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    • Application(array)
      • id419
      • user_id85
      • trial_status_id1
      • abstract_of_study<div>\n Plasmodium falciparum (P. falciparum) malaria is a major cause of morbidity and mortality in Africa. Siaya County in Western Kenya is holoendemic for malaria(1). At the Siaya Hospital outpatient department alone, data abstraction shows 2000-4000 cases of uncomplicated malaria seen at the facility annually.</div>\n<div>\n Concurrent with preventive measures, World Health Organization (WHO) guidelines recommend artemisinin-based combination therapies (ACT) are used to treat uncomplicated P. falciparum malaria to prevent development of resistance and to improve treatment outcome.</div>\n<div>\n  </div>\n<div>\n Artemisinin produces rapid clearance of parasitemia and resolution of symptoms by reducing parasite number by 100- to 1000-fold per asexual cycle of the parasite. Artemisinin and its derivatives are rapidly eliminated. It is therefore given in combination with 4-aminoquinoline drugs which have a longer half-life. This requires a three day course of treatment. Evidence suggests that compliance to this 3-day regimen is low, thereby reducing treatment effectiveness. In addition, emergence of resistance to artemisinin may become a considerable problem in the coming years(2). New drug combinations are required. Particularly, effective single dose combination treatments will likely improve effectiveness.</div>\n<div>\n  </div>\n<div>\n A fixed dose combination of two therapeutic agents Ferroquine (FQ) and Artefenomel (OZ439) will be evaluated as single day-single dose treatment of uncomplicated malaria. This will be a Phase IIb safety, tolerability, pharmacokinetic and efficacy trial. The target population will be adults <70 years old and children >6months with uncomplicated malaria.</div>\n<div>\n Patients will be randomized to up to four treatment arms containing both FQ and OZ439. The dose of OZ439 will be fixed at 800mg in each arm. However the dose of FQ will vary with each arm receiving a higher dose than the previous cohort. The primary outcome will be PCR-adjusted Adequate Clinical and Parasitological Response (ACPR) at day 28. Total follow up time per patient will be at least 67 days from study entry to close out. Safety endpoints will be based on clinical and laboratory identified adverse events.</div>\n<div>\n If this combination proves to be effective and safe in areas where artemisinin-resistant P. falciparum is absent or rare complementary trials may be performed to determine whether a similar clinical benefit exists in locations where resistance to artemisinin and chloroquine have developed.</div>\n
      • study_title<div>\n A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) with Artefenomel (OZ439) in Adults and Children with Uncomplicated Plasmodium falciparum Malaria.</div>\n
      • laymans_summary<p style=\"margin-left:36.0pt;\">\n Malaria is responsible for considerable morbidity and mortality, particularly in Western Kenya. Malaria is best treated with a combination of drugs as this prevents development of drug resistance. Currently, uncomplicated malaria is treated with a three day course of treatment which is associated with considerable defaulting-many patients do not complete the three day dose.</p>\n<p style=\"margin-left:36.0pt;\">\n This is a proposed phase IIb trial of a single dose treatment of ferroquine and artefenomel in the treatment of uncomplicated malaria. Patients will be entered into the trial based on their age groups, beginning with older patients. All patients will receive the same dose (or a weight adjusted dose) of Artefenomel 800mg, but will be randomly assigned to varying doses of Ferroquine. The objective is to determine safety, tolerability and efficacy of the combination of treatment.   </p>\n
      • short_titleFALCI Study
      • protocol_noECCT/15/11/05
      • version_no1.0
      • date_of_protocol20-11-2014
      • study_drugFerroquine & Artefenomel
      • disease_conditionMalaria
      • 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_nameFerroquine & Artefenomel
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresstsang@kemricdc.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_countries0
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Tony Sang
      • declaration_date116-11-2015
      • declaration_principal_investigatorDr Grace Kaguthi
      • declaration_date216-11-2015
      • placebo_presentNo
      • study_objectives<p style=\"margin-left:36.0pt;\">\n <em>Primary Objective</em></p>\n<p style=\"margin-left:18.0pt;\">\n To determine whether a single dose combination of OZ439/FQ is an efficacious treatment for uncomplicated Plasmodium falciparum (P. falciparum) malaria in adults and children</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:54.0pt;\">\n <em>Secondary Objectives</em></p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n To evaluate the efficacy of OZ439/FQ:</li>\n <li>\n To determine the incidence of recrudescence and re-infection</li>\n <li>\n To determine the time to relief of fever and parasite clearance</li>\n <li>\n To evaluate the safety and tolerability of OZ439/FQ</li>\n <li>\n To evaluate the pharmacokinetics of OZ439/FQ:</li>\n <li>\n To characterize the pharmacokinetics of OZ439 in plasma, FQ and its active metabolite SSR97213 in blood</li>\n <li>\n To determine the blood/plasma ratio for FQ and SSR97213 in some patients at limited time points in selected sites.</li>\n <li>\n To further explore efficacy of OZ439/FQ:</li>\n <li>\n To evaluate the proportion of patients with gametocytes at each parasitological assessment</li>\n <li>\n To characterize gametocyte carriage</li>\n <li>\n To evaluate the relationship between Adequate Clinical &</li>\n <li>\n Parasitological Response (ACPR) and exposure to OZ439/FQ</li>\n</ol>\n<p style=\"margin-left:54.0pt;\">\n  </p>\n<p style=\"margin-left:36.0pt;\">\n m. To explore the relationship between Kelch-13 genotype and parasite clearance kinetics</p>\n
      • principal_inclusion_criteria<ul>\n <li>\n <span style=\"font-size:12px;\"> Male or female patient aged > 6 months old and < 70 years old</span>\n <ul>\n <li>\n <span style=\"font-size:12px;\">- Cohort 1 = 14 years<age<70 35=\"\" and=\"\" body=\"\" span=\"\" weight=\"\" years=\"\"></age<70></span></li>\n <li>\n <span style=\"font-size:12px;\">- Cohort 2 = 5 years < age ≤ 14 years</span></li>\n <li>\n <span style=\"font-size:12px;\">- Cohort 3 = 2 years < age ≤ 5 years</span></li>\n <li>\n <span style=\"font-size:12px;\">- Cohort 4 = 6 months < age ≤ 2 years</span></li>\n </ul>\n </li>\n <li>\n <span style=\"font-size:12px;\">Body weight ≥ 5 kg and ≤ 90 kg.</span></li>\n <li>\n <span style=\"font-size:12px;\">Presence of mono-infection by P. falciparum with: Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and, microscopically (blood smear) confirmed parasite infection, ranging from 1000 to 100 000 asexual parasites/μL of blood.</span></li>\n <li>\n <span style=\"font-size:12px;\">Informed Consent Form signed by the patient or parent</span></li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Presence of severe malaria (according to WHO definition)</li>\n <li>\n Anti-malarial treatment:\n <ul>\n <li>\n With piperaquine -based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine (SP) within the previous 6 weeks (after their inhibition of new infections has fallen below 50%).</li>\n <li>\n With amodiaquine or chloroquine within the previous 4 weeks. </li>\n <li>\n With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days.</li>\n <li>\n With any herbal products or traditional medicines, within the past 7 days.</li>\n </ul>\n </li>\n <li>\n Known history or evidence of clinically significant disorders</li>\n <li>\n Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest which are: P-gp substrates, CYP2D6 main substrates and/or strong CYP2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers</li>\n <li>\n Mixed Plasmodium infection</li>\n <li>\n Severe vomiting</li>\n <li>\n Severe malnutrition</li>\n <li>\n Laboratory parameters with clinical significant abnormalities and/or reaching critical values. For Liver Function Test: aspartate transferase [AST >2 upper limit of normal (ULN)], or alanine transferase [ALT >2 ULN] or total bilirubin [>1.5 ULN]. </li>\n <li>\n Presence of Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBs Ag) or Hepatitis C antibody (HCV Ab)</li>\n</ul>\n<div>\n <ul>\n <li>\n Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance</li>\n <li>\n Female patient of child bearing potential or male patient having a partner of child bearing potential not willing to use an effective contraceptive(s) method(s) for the duration of the study</li>\n <li>\n Positive pregnancy test at study screening for female participants of childbearing potential.</li>\n <li>\n Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc-interval or any clinical condition known to prolong the QTc interval e.g., patients with a history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.</li>\n <li>\n QTcF > 450 ms at screening or pre-dose.</li>\n <li>\n Hypokalemia (<3.5 mmol/L), hypocalcemia (< 2.0 mmol/L) or hypomagnesemia (< 0.5 mmol/L) at screening or pre-dose.</li>\n <li>\n Any treatment known to induce a lengthening of QT interval</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n PCR-adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28</p>\n<div>\n <u>Secondary Endpoints</u></div>\n<div>\n Efficacy Endpoints</div>\n<div>\n • PCR - adjusted ACPR at Day 42 and 63.</div>\n<div>\n • PCR - crude ACPR at Day 28, 42 and 63.</div>\n<div>\n • Kaplan Meier analysis for:</div>\n<div style=\"margin-left: 40px;\">\n - Time to re-emergence</div>\n<div style=\"margin-left: 40px;\">\n - Time to recrudescence</div>\n<div style=\"margin-left: 40px;\">\n - Time to re-infection</div>\n<div>\n • Parasite clearance time (PCT).</div>\n<div>\n • Fever clearance time (FCT).</div>\n<div>\n • Parasite reduction rate (PRR).</div>\n<div>\n  </div>\n<div>\n <u>Safety Endpoints</u></div>\n<div>\n • Adverse events, including Serious Adverse Events (SAE), Adverse</div>\n<div>\n Event of Special Interest (AESI) and Treatment Emergent Adverse</div>\n<div>\n Event (TEAE).</div>\n<div>\n • Clinical laboratory tests, vital signs and ECG, including:</div>\n<div style=\"margin-left: 40px;\">\n - Liver Function test (LFT)</div>\n<div style=\"margin-left: 40px;\">\n - QTc assessment</div>\n<div>\n • Physical examination and clinical signs and symptoms related to uncomplicated P. falciparum malaria (fever, dizziness, headache,</div>\n<div>\n nausea, anorexia, vomiting, diarrhea, itching, urticaria, skin rash, abdominal pain, joint pain, muscle pain, palpitations, sleep problems,</div>\n<div>\n confusion, hearing problems, vision problems, and fatigue).</div>\n<div>\n  </div>\n<div>\n <u>Pharmacokinetic (PK) Endpoints</u></div>\n<div>\n • Pharmacokinetic parameters (mainly CL/F, Vss/F, Cmax, AUC as relevant) of OZ439 in plasma, FQ and SSR97213 in blood and plasma</div>\n<div>\n • Blood/plasma ratio for FQ and SSR97213 (some patients in selected sites).</div>\n<div>\n  </div>\n<div>\n <u>Exploratory Endpoints</u></div>\n<div>\n • Time to clearance of gametocytemia on blood smear for patients with gametocytes at baseline,</div>\n<div>\n • Time to appearance of gametocytemia on blood smear for patients with no gametocytes at baseline and time to clearance</div>\n<div>\n • RT-PCR to measure gametocyte maturation stage (expression of Pfs25 mRNA)</div>\n<div>\n • Correlation between Kelch-13 genotype status and parasite clearance kinetics</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic1
      • 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_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n The Siaya Hospital outpatient department sees between 300 and 500 confirmed malaria cases every month aged 6 months to up to 70 years. There are no anticipated challenges to accruing the required sample size. There is also capacity to meet protocol safety monitoring by availability of ECG machine, reliable and reproducible laboratories and availability of trained and experienced microscopists to review slides. There is a pool of clinical research staff experienced in quality and regulatory requirements, informed consent and data entry. The site's clinical research staff include the following:</p>\n<ul>\n <li>\n Principal Investigator - Dr Grace Kaguthi, MBChB,MSc</li>\n <li>\n Co-Investigator - Dr Videlis Nduba, MBChB, MPH</li>\n <li>\n Study Medical Officer - Dr Michael Mutua, MBChB</li>\n <li>\n Pharmacist - Dr Tony Sang, BPharm</li>\n <li>\n Clinical Officers x 3</li>\n <li>\n Pharmaceutical Tecnologist x 2</li>\n <li>\n Nurses x 8</li>\n <li>\n Lab Technicians x 2</li>\n <li>\n Phlebotomist x 1</li>\n <li>\n Data Officers x 3</li>\n <li>\n QA/QC officers x 3</li>\n</ul>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI Scientific and Ethics Review Unit approved the protocol on 02-sep-2015</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration1-2 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • 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_statesEighteen sites
      • number_of_sitesFour sites
      • multi_country_listAfrican Countries: Gabon, Uganda, Kenya, Burkina Faso, Benin & Mozambique\nAsia-Pacific Region: Indonesia & Vietnam
      • data_monitoring_committeeYes
      • total_enrolment_per_site0 to 120 participants
      • total_participants_worldwide662
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentYes
      • 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_consentYes
      • subjects_specifyMinor participants i.e. below 18 years of age for whom Informed Consent Form will be signed by their legally acceptable representative. In addition, in accordance with local regulation, minors aged ≥ 13 years with capacity for writing will sign an Assent Form.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameGrace
      • investigator1_middle_nameKiringa
      • investigator1_family_nameKaguthi
      • investigator1_qualificationMBChB, MSc
      • investigator1_professional_addressKEMRI/Centre for Respiratory Diseases Research (CRDR)
      • investigator1_telephone+254 729 489743
      • investigator1_emailskiringa@gmail.com
      • organisations_transferred_Yes
      • number_participants120
      • notification
      • approval_date01-02-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-02-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n As attached</p>\n
      • implication_results<p>\n No impact on current practice due to futility.</p>\n
      • quantity_imported279
      • quantity_dispensed36
      • quantity_destroyed279
      • quantity_exported0
      • balance_site 0
      • final_date0000-00-00
      • modified2021-01-06 14:13:54
      • created2015-09-15 15:12:37
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id285
        • application_id419
        • given_nameGrace
        • middle_nameKiringa
        • family_nameKaguthi
        • qualificationMBChB, MSc
        • professional_addressKEMRI/Centre for Respiratory Diseases Research (CRDR)
        • telephone+254 729 489743
        • emailskiringa@gmail.com
        • created2015-09-15 15:34:53
        • modified2020-02-28 14:56:33
    • SiteDetail(array)
      • 0(array)
        • id338
        • application_id419
        • county_id41
        • site_nameKEMRI Center for Respiratory Diseases Research
        • physical_addressSiaya County Referral Hospital, Siaya
        • contact_details+254 729489743
        • contact_personDr Grace Kaguthi
        • site_capacity(null)
        • misc(null)
        • created2015-09-15 15:34:53
        • modified2020-02-28 14:56:33
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id343
        • application_id419
        • county_id42
        • site_nameKEMRI Walter Reed Kombewa
        • physical_addressKombewa District Hospital
        • contact_detailsjanet.oyieko@usamru-k.org, Tel:+254 721 996988
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2015-10-09 13:03:57
        • modified2020-02-28 14:56:33
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id344
        • application_id419
        • county_id42
        • site_nameKEMRI Kisumu
        • physical_addressJaramogi Oginga Odinga Teaching & Referral Hospital
        • contact_detailsPhone: +254 733 812613 Email: ogutu6@gmail.com
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2015-10-09 13:03:57
        • modified2020-02-28 14:56:33
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id222
        • application_id419
        • sponsorSanofi Aventis
        • sponsor_typeIndustry
        • contact_personValerie Nicol
        • address1 Avenue Pierre Brossolette 91385 CHILLY-MAZARIN CEDEX France
        • telephone_number+33 (0)1 53 77 40 00
        • fax_number
        • cell_number+33 (0)1 53 77 40 00
        • email_addressvalerie.Nicol@sanofi.com
        • created2015-09-15 15:34:53
        • modified2020-02-28 14:56:33
  • 1(array)
    • Application(array)
      • id923
      • user_id613
      • trial_status_id7
      • abstract_of_study<div>\n A safe and effective HIV vaccine would be the cornerstone for cost-effective, user-independent</div>\n<div>\n prevention methods against HIV infection. Most of the successfully licensed vaccines for</div>\n<div>\n prevention of infections have historically relied upon aluminum salt (alum) formulations as</div>\n<div>\n adjuvants because they generally improve protective antibody magnitudes over the vaccine antigen</div>\n<div>\n alone and are reliably safe.</div>\n<div>\n Antibodies are the most commonly recognized correlate of vaccine protection from infection;</div>\n<div>\n however, the possible protective HIV antibody levels, which were induced by the modestly</div>\n<div>\n protective RV144 vaccine regimen with alum, rapidly decayed. Potentially, a novel, highly</div>\n<div>\n selective adjuvant combined with the correctly sequenced HIV antigen could slow antibody decay,</div>\n<div>\n increase antibody magnitude, and induce antibodies of appropriate functional response.</div>\n<div>\n RV460 is an exploratory study that will assess the safety, tolerability, and immunogenicity of a</div>\n<div>\n vaccine regimen consisting of priming with an Env-C Plasmid DNA vaccine (with or without</div>\n<div>\n novel adjuvants) when given with or without adjuvanted HIV Env gp145 C.6980 protein vaccine</div>\n<div>\n and boosting with adjuvanted gp145 C.6980 protein with or without the gp120 DNA vaccine. The</div>\n<div>\n study will be carried out at the KEMRI/US Army Medical Research Directorate-Africa</div>\n<div>\n (USAMRD-A), Clinical Research Centre, Kericho; and 126 healthy adults will be enrolled.</div>\n<div>\n Participants enroll randomly into one of seven groups which have 15/3 vaccine/placebo recipients</div>\n<div>\n per group. Each participant will receive six injections (prime at week 0, 4, 12; boost at week 20,</div>\n<div>\n 32 and 56) followed up for a total of 108 weeks.</div>\n<div>\n Study objectives will be met by the testing of blood samples from all participants. Willing and</div>\n<div>\n eligible participants have the option to provide lymph node and mucosal secretion samples (semen,</div>\n<div>\n cervicovaginal, rectal), which will provide the data for objectives 2 and the sub-objections.</div>\n<div>\n Exploratory objectives may be met by genetic analysis including but not limited to Human</div>\n<div>\n Leukocyte Antigen (HLA) subtyping.</div>\n
      • study_title<div>\n A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and Immunogenicity of</div>\n<div>\n Priming with Env-C Plasmid DNA Vaccine Alone, with Different Adjuvants, or with an</div>\n<div>\n Adjuvanted HIV Env gp145 C.6980 Protein Vaccine and Boosting with the Adjuvanted</div>\n<div>\n HIV Env gp145 C.6980 Protein Vaccine with or without the Env-C Plasmid DNA Vaccine</div>\n<div>\n in Healthy HIV Uninfected Adults in Kenya</div>\n
      • laymans_summary<div>\n The Kenya Medical Research Institute (KEMRI) in collaboration with the U.S. Military HIV</div>\n<div>\n Research Program (MHRP) is conducting a study on HIV vaccines. A vaccine is a medical product</div>\n<div>\n given to prevent certain diseases, most often infectious diseases. The vaccine may educate the</div>\n<div>\n human body to form a defensive response to try to prevent the disease from the beginning or taking</div>\n<div>\n hold of the body. This defensive response called the immune response, and it is the body’s way</div>\n<div>\n to fight infections.</div>\n<div>\n The experimental HIV vaccines tested in this study are Env-C Plasmid DNA and HIV Env gp145</div>\n<div>\n C.6980 protein given with different adjuvants to increase the immune response. An adjuvant is a</div>\n<div>\n substance added to vaccines that can help to make the vaccine more effective by improving the</div>\n<div>\n immune response or causing the immune response to last longer than without the adjuvant. These</div>\n<div>\n adjuvants are mixed with the vaccines and injected into the muscle or placed on top of the skin.</div>\n<div>\n The HIV vaccines contain a piece of genetic material or a protein copied from the HIV virus cover</div>\n<div>\n (Env), but they do not contain the virus itself. The vaccines cannot cause HIV infection or</div>\n<div>\n Acquired Immune Deficiency Syndrome (AIDS).</div>\n<div>\n The purpose of this study is to find out if the study vaccines with adjuvants cause side effects and</div>\n<div>\n are tolerable, whether humans respond, (develop immune responses) to the vaccines, and how long</div>\n<div>\n the effects of study vaccines last. This study will also compare the effects (both good and bad) of</div>\n<div>\n the study vaccines with adjuvants and adjuvant patch to those of placebo injections and adjuvant</div>\n<div>\n patch. The placebo will consist of saline (sterile saltwater), look just like the study vaccines with</div>\n<div>\n adjuvants and will be given the same way, but will have no active vaccine or adjuvant in it.</div>\n<div>\n Study objectives will be met by the testing of blood samples from all participants. Willing and</div>\n<div>\n eligible participants have the option to provide lymph node and mucosal secretion samples (semen,</div>\n<div>\n cervicovaginal, rectal) will provide the data for objectives 2 and the sub-objections.</div>\n<div>\n The sponsor of this study is National Institute of Allergy and Infectious Diseases (NIAID) Division</div>\n<div>\n of AIDS (DAIDS), and the Military HIV Research Program (MHRP), a part of the Walter Reed</div>\n<div>\n Army Institute of Research (WRAIR), funds it. A total of 126 participants will take part in this</div>\n<div>\n study.</div>\n
      • short_titleRV 460 HIV Vaccine Trial
      • protocol_noECCT/20/07/02
      • version_no2.0
      • date_of_protocol29-02-2020
      • study_drugEnv-C Plasmid DNA vaccine; HIV-1 ENV GP145 C.6980; DMLT; ALF43; REHYDRAGEL®; 0.9% SODIUM CHLORIDE FOR INJECTION
      • disease_conditionHIV
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • 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
      • comparatorYes
      • comparator_name0.9% SODIUM CHLORIDE FOR INJECTION
      • comparator_registeredYes
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressKericho.DRS@usamru-k.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_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • 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_plan0
      • applicant_contractual_agreement1
      • declaration_applicantJosphat Kosgei
      • declaration_date130-07-2020
      • declaration_principal_investigatorJosphat Kosgei
      • declaration_date230-07-2020
      • placebo_presentYes
      • study_objectives<div>\n PRIMARY</div>\n<div>\n Assess the safety and tolerability (including reactogenicity) of Env-C Plasmid DNA given IM,</div>\n<div>\n alone, admixed with ALF43 adjuvant, topically applied with dmLT adjuvant, or given with an</div>\n<div>\n adjuvanted HIV Env gp145 C.6980 protein and followed by adjuvanted HIV Env gp145</div>\n<div>\n C.6980 protein boost IM immunizations, with or without Env-C Plasmid DNA.</div>\n<div>\n 2.6.2 SECONDARY</div>\n<div>\n 1. Determine whether the adjuvants under study improve the immunogenicity of</div>\n<div>\n the Env-C Plasmid DNA priming.</div>\n<div>\n 2. Determine whether the addition of ALF43 to the Rehydragel® –HIV Env</div>\n<div>\n gp145 C.6980 protein boost further improves the immune response to HIV Env</div>\n<div>\n gp145 C.6980 protein.</div>\n<div>\n 3. Determine whether adjuvants improve humoral responses across vaccination</div>\n<div>\n regimens.</div>\n<div>\n 4. Evaluate the influence of various adjuvants on cellular immune responses.</div>\n<div>\n 5. Describe mucosal humoral responses across vaccination regimens in</div>\n<div>\n cervicovaginal and rectal secretions and semen.</div>\n<div>\n 2.6.3 EXPLORATORY</div>\n<div>\n 1. Characterize B-cell functional specificities for each vaccination regimen.</div>\n<div>\n 2. Characterization of innate immunity.</div>\n<div>\n 3. Assess the innate/gene expression induced across vaccination regimens (DNA</div>\n<div>\n microarray, RNA sequencing) to compare relative influence of various</div>\n<div>\n adjuvants in the gene expression profiles of sorted T cell, B cell and innate cell</div>\n<div>\n subsets.</div>\n<div>\n 4. Perform systems serology analyses.</div>\n
      • principal_inclusion_criteria<div>\n INCLUSION CRITERIA</div>\n<div>\n 1. Healthy, male and female participant aged 18 to 40 years and available for 26</div>\n<div>\n months</div>\n<div>\n 2. Must be at low risk for HIV infection per investigator assessment and using</div>\n<div>\n the study risk assessment tool.</div>\n<div>\n 3. Must be able to understand and complete the informed consent process.</div>\n<div>\n 4. Must be capable of reading English or Kiswahili.</div>\n<div>\n 5. Must agree to a home visit.</div>\n<div>\n 6. Must complete a Test of Understanding (TOU) before enrollment. Must</div>\n<div>\n answer 9 out of 10 questions correctly, with a maximum of three attempts.</div>\n<div>\n 7. Must be in good general health without a clinically significant medical history.</div>\n<div>\n 8. HIV-uninfected per diagnostic algorithm within 45 days of enrollment.</div>\n<div>\n 9. Laboratory values:</div>\n<div>\n • Hemoglobin:</div>\n<div>\n 12.5-18.1 g/dL men</div>\n<div>\n 11.0-16.1 g/dL women</div>\n<div>\n • White Cell Count:</div>\n<div>\n 2.7-7.7 x 103 cells/μL men</div>\n<div>\n 3.0-9.1 x 103 cells/μL women</div>\n<div>\n • Platelets:</div>\n<div>\n 125-370 103 cells/μL men</div>\n<div>\n 125-444 103 cells/μL women</div>\n<div>\n • ALT and AST: ≤1.25 institutional upper limit of the reference range</div>\n<div>\n Creatinine: ≤1.25 institutional upper limit of the reference range</div>\n<div>\n • Urinalysis: (dipstick) for blood and protein less than 1+ and negative glucose</div>\n<div>\n Female-Specific Criteria:</div>\n<div>\n 10. Negative urine pregnancy test for women at screening, the day of each</div>\n<div>\n vaccination, and before any invasive procedure.</div>\n<div>\n 11. Already using and commits to continued use of an adequate birth control</div>\n<div>\n method for 45 days before to the first vaccine/placebo vaccination and for at</div>\n<div>\n least 90 days after the final vaccine/placebo vaccination. Adequate birth</div>\n<div>\n control is defined as follows: Contraceptive medications delivered orally,</div>\n<div>\n intramuscularly, vaginally, or implanted, underneath the skin, surgical</div>\n<div>\n methods (hysterectomy or bilateral tubal ligation), condoms with spermicide,</div>\n<div>\n diaphragms, intrauterine device (IUD), vasectomy in a monogamous partner,</div>\n<div>\n or abstinence.</div>\n
      • principal_exclusion_criteria<div>\n EXCLUSION CRITERIA</div>\n<div>\n A history of:</div>\n<div>\n 1. Three or more sexual partners in the previous 24 weeks</div>\n<div>\n 2. Commercial sex work</div>\n<div>\n 3. Non-adherence to condom use in the absence of a long-term monogamous</div>\n<div>\n relationship</div>\n<div>\n 4. Intravenous drug use in the previous year.</div>\n<div>\n 5. A sexually transmitted infection in the previous 24 weeks</div>\n<div>\n 6. Asplenia: any condition resulting in the absence of a functional spleen</div>\n<div>\n 7. Bleeding disorder diagnosed by a medical doctor (e.g., factor deficiency,</div>\n<div>\n coagulopathy, or platelet disorder requiring special precautions)</div>\n<div>\n 8. Breastfeeding or pregnant (positive pregnancy test) women or planning to</div>\n<div>\n become pregnant during the window between study enrollment and three</div>\n<div>\n months after the last vaccination visit.</div>\n<div>\n 9. Any past, ongoing, or in remission history of treated or untreated autoimmune</div>\n<div>\n disease.</div>\n<div>\n 10. Has known active Hepatitis B virus infection (or positive HBsAg).</div>\n<div>\n 11. History of anaphylaxis or other serious adverse reaction to vaccines or allergies</div>\n<div>\n or reactions likely to be exacerbated by any component of the vaccine and</div>\n<div>\n placebo, including antibiotics or excipients</div>\n<div>\n 12. Absolute Neutrophil Count (ANC):</div>\n<div>\n <1.0 x 103 cells/μL</div>\n<div>\n 13. Participant has received any of the following substances:</div>\n<div>\n • Chronic use of therapies that may modify immune response, such as intravenous</div>\n<div>\n (IV) immune globulin and systemic corticosteroids (in doses of >20 mg/day</div>\n<div>\n prednisone equivalent for periods exceeding 10 days)</div>\n<div>\n • The following exceptions are permitted and will not exclude study participation:</div>\n<div>\n o use of corticosteroid nasal spray for rhinitis,</div>\n<div>\n o topical corticosteroids for an acute uncomplicated dermatitis; or</div>\n<div>\n o A short course (10 days or less, or a single injection) of corticosteroid for a</div>\n<div>\n non-chronic condition (based on investigator clinical judgment) at least 2</div>\n<div>\n weeks before enrollment.</div>\n<div>\n 14. Blood products within 120 days before HIV screening</div>\n<div>\n 15. Immunoglobulins within 30 days before HIV screening</div>\n<div>\n 16. Any experimental vaccine containing an adjuvant other than aluminum or an</div>\n<div>\n adjuvant not approved by the FDA or European Medicines Agency (EMA) as</div>\n<div>\n part of a licensed vaccine.</div>\n<div>\n 17. CERVARIX vaccine against HPV (containing AS04)</div>\n<div>\n 18. Receipt of any investigational HIV vaccine, investigational research agents or</div>\n<div>\n vaccine within 30 days before enrollment.</div>\n<div>\n 19. Anti-tuberculosis prophylaxis or therapy during the past 90 days before</div>\n<div>\n enrollment</div>\n<div>\n 20. Any psychiatric, social condition, occupational reason, or other responsibility</div>\n<div>\n that, in the judgment of the investigator, is a contraindication to protocol</div>\n<div>\n compliance or impairs a participant’s ability to give informed consent</div>\n<div>\n 21. Major psychiatric illness and or substance abuse problems during the past 12</div>\n<div>\n months that, in the opinion of the investigator, would preclude participation</div>\n<div>\n 22. History of atopy or significant skin conditions</div>\n<div>\n 23. Study site employees who are involved in the protocol and or may have direct</div>\n<div>\n access to the study-related area</div>\n<div>\n Final evaluation of eligibility is based on the medical judgment of the investigator. The PSRT will</div>\n<div>\n also remain available to PI for consultation if desired.</div>\n
      • primary_end_points<div>\n The primary endpoints of this Phase 1 study are related to the safety, reactogenicity and tolerability</div>\n<div>\n of the Env-C Plasmid DNA vaccine regimens. These will be monitored by PSRT and SMC as</div>\n<div>\n appropriate, and SAE), AEs and PIMMC will be recorded until the end of the trial.</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans1
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n USAMRD-A is a Special Foreign Activity of WRAIR, Silver Spring, Maryland (MD). USAMRDA</div>\n<div>\n includes the Kericho, Kenya unit affiliated through a Cooperative Agreement with KEMRI. The</div>\n<div>\n unit was activated on a temporary basis in 1969 at the invitation of the Government of Kenya to</div>\n<div>\n study trypanosomiasis. The success of that initial venture led to the establishment of a permanent</div>\n<div>\n activity in 1973. Over the past 45 years, research has been conducted on malaria, trypanosomiasis,</div>\n<div>\n leishmaniasis, entomology, HIV/AIDS, Polio, Ebola, Tuberculosis (TB), arboviruses, and other</div>\n<div>\n infectious diseases, with more than 250 manuscripts published.</div>\n<div>\n The USAMRD-A HIV Program is a component of MHRP. In Kenya, the HIV Program field site</div>\n<div>\n is located at KEMRI/USAMRD-A/Clinical Research Center (CRC) about 260 kilometers</div>\n<div>\n northwest of Nairobi along the Nairobi-Kisumu highway in the rural Kenyan town of Kericho.</div>\n<div>\n Kericho’s county population is approximately 752,396 (2009 census), although the larger</div>\n<div>\n catchment area for both HIV research and treatment is approximately 3 million covering the</div>\n<div>\n southern portion of the Rift Valley Province. Kericho is located among the African Highlands in</div>\n<div>\n the Rift Valley and well known for the growing of tea that forms the rolling “seas of green” within</div>\n<div>\n the tea plantations. The primary industry in this region is tea farming, with two large international</div>\n<div>\n tea companies namely Finlay’s Kenya Ltd and Unilever Tea Kenya Ltd, centered in Kericho</div>\n<div>\n County Referral Hospital (KCRH).</div>\n<div>\n Kericho was ranked as the twentieth richest county in Kenya in the 2005/06 National Integrated</div>\n<div>\n Household Budget Survey. Income in Kericho comes mainly from agricultural activities, with</div>\n<div>\n about 40-50% of the population living below the poverty line. The annual national gross domestic</div>\n<div>\n product per capita in 2013 averaged 1,245.51 U.S. dollars (USD). In Kenya, the age of majority</div>\n<div>\n (i.e. legal age of recognized adulthood or independence) is 18 years. The Kenyan national literacy</div>\n<div>\n level according to the Kenya Adult Literacy Survey report published in March 2007 by the Kenya</div>\n<div>\n National Bureau of Statistics was 64%. In Kericho, the literacy level is 74.3% in men and 68.9%</div>\n<div>\n in women. The government through a network of hierarchical public hospitals, health centers,</div>\n<div>\n primarily provides the healthcare system in the larger Kericho area (southern Rift Valley) and</div>\n<div>\n dispensaries ran by the Kenya Ministry of Health (MoH). The government health facilities do not</div>\n<div>\n charge for treatment but levy a small fee for facility maintenance, which can be waived for those</div>\n<div>\n not able to pay. In addition to government health care facilities, there are a few faith-based and</div>\n<div>\n private health care facilities providing services at a small fee. Access to most health care facilities</div>\n<div>\n is good given that there exists a reliable public transport system in the region.</div>\n<div>\n The KEMRI/USAMRD-A CRC is the primary HIV research site in USAMRD-A. Situated on the</div>\n<div>\n grounds of the KCRH/MoH, the 55,050 square feet CRC supports both HIV research and care and</div>\n<div>\n treatment in the southern Rift Valley Province. The CRC is composed of a clinical area including</div>\n<div>\n a central pharmacy that can support both vaccine and therapeutic studies as well as provide</div>\n<div>\n additional non-study medicines for HIV and other non-study related care. The CRC is a designated</div>\n<div>\n satellite HIV and TB clinic under the KCRH.</div>\n<div>\n The CRC laboratory is Kenya’s first and the only College of American Pathologist (CAP)</div>\n<div>\n accredited laboratory and boasts of a state-of-the-art Information Technology (IT) center that</div>\n<div>\n supports both HIV research and treatment programs. Both the CRC pharmacy and laboratory are</div>\n<div>\n approved by NIAID/DAIDS to participate in DAIDS sponsored vaccine (Site #31352) and</div>\n<div>\n therapeutics AIDS Clinical Trials Group (ACTG Site #12501); International Maternal Pediatric</div>\n<div>\n Adolescent AIDS Clinical Trials (IMPAACT site #5121) studies, the only research site with such</div>\n<div>\n approval in Kenya.</div>\n
      • other_details_explanation<p>\n Similar studies has been done in the host country (USA) before.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU</p>\n<p>\n WRAIR IRB</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration26 months
      • 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_comparator0.9% Normal Saline
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI/US MRDA-A/K, KERICHO
      • single_site_physical_addressHOSPITAL ROAD
      • single_site_contact_personJosphat Kosgei
      • single_site_telephone254729110122
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteOne site only
      • total_participants_worldwide126
      • 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_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_nameJosphat
      • investigator1_middle_nameKiprop
      • investigator1_family_nameKosgei
      • investigator1_qualificationMBChB; MSc; DLSHTM
      • investigator1_professional_addressKEMRI WRP
      • investigator1_telephone254 729 110 122
      • investigator1_emailjosphat.kosgei@usamru-k.org
      • organisations_transferred_Yes
      • number_participants126
      • notification
      • approval_date19-10-2020
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted16-09-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonStudy approved by the Expert Committee
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-11-12 12:39:41
      • created2020-07-30 11:57:43
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id570
        • application_id923
        • given_nameJosphat
        • middle_name
        • family_nameKosgei
        • qualificationMBChB; MSc; DLSHTM
        • professional_addressKEMRI WRP
        • telephone254 729 110 122
        • emailjosphat.kosgei@usamru-k.org
        • created2020-07-30 12:20:14
        • modified2021-09-16 13:14:50
    • SiteDetail(array)
      • 0(array)
        • id799
        • application_id923
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2020-07-30 12:20:14
        • modified2021-09-16 13:14:50
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id444
        • application_id923
        • sponsorUS NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
        • sponsor_typeOthers
        • contact_person
        • addressBethesda, Maryland
        • telephone_number301 500 3688
        • fax_number
        • cell_number301 500 3688
        • email_addresscpolyak@hivresearch.org
        • created2020-07-30 12:20:14
        • modified2021-09-16 13:14:50
  • 2(array)
    • Application(array)
      • id141
      • user_id77
      • trial_status_id5
      • abstract_of_study<div>\n Titke: Plus HIV Primary Care versus HIV Primary Care Alone to Prevent the Sexual Transmission of</div>\n<div>\n HIV-1 In Serodiscordant Couples</div>\n<div>\n Purpose: The purpose of this study is to determine whether antiretroviral therapy (ART) can</div>\n<div>\n prevent the sexual transmission of HIV-1 in HIV-1 serodiscordant couples.</div>\n<div>\n Design: The study is a Phase III, two-arm, randomized, controlled, multi-center trial. This trial</div>\n<div>\n consists of a run-in period, which has been completed, and a full study.</div>\n<div>\n Study Population: HIV serodiscordant couples in which the HIV-infected partner is ART-naive and</div>\n<div>\n has a CD4+ cell count of 350-550 cells/mm3.</div>\n<div>\n Study Size: Approximately 1750 couples total</div>\n<div>\n Study Arms: HIV-infected index cases will be assigned at random in a 1:1 ratio to one of two</div>\n<div>\n treatment arms:</div>\n<div>\n Arm 1: ART upon enrollment plus HIV primary care.</div>\n<div>\n Arm 2: HIV primary care without initiation of ART until the participant has two consecutive</div>\n<div>\n measurements of a CD4+ cell count within or below the range of 200-250</div>\n<div>\n cells/mm3, or develops an AIDS-defining illness.</div>\n<div>\n The ART drugs provided through the study include Combivir® [3TC/zidovudine(ZDV)],</div>\n<div>\n efavirenz [EFV], atazanavir [ATV], nevirapine [NVP], tenofovir [TDF], lamivudine [3TC],</div>\n<div>\n didanosine [ddI-EC], stavudine [d4T], Kaletra®/Aluvia® [lopinavir(LPV)/ritonavir (r)], and</div>\n<div>\n Truvada® [emtricitabine (FTC)/tenofovir (TDF)].</div>\n<div>\n Study Duration: The duration of the full study will be approximately 78 months total. Accrual</div>\n<div>\n into the study will require approximately 18 months total, and all couples will be followed until</div>\n<div>\n the last couple enrolled completes their 60-month follow-up visit.</div>\n<div>\n Study Objectives:</div>\n<div>\n The primary objective of the study is to compare the rates of HIV infection among partners of</div>\n<div>\n HIV-infected participants in the two study arms below:</div>\n<div>\n (1) ART upon enrollment plus HIV primary care.</div>\n<div>\n (2) HIV primary care without initiation of ART until the participant has two consecutive</div>\n<div>\n measurements of a CD4+ cell count within or below the range of 200-250 cells/mm3,</div>\n<div>\n or develops an AIDS-defining illness.</div>\n<div>\n HPTN 052 Final Version 3.0, 20 November 2006 Page 16 of 173</div>\n<div>\n  </div>\n<div>\n The secondary objectives of the study are to:</div>\n<div>\n • Determine the long-term safety of two antiretroviral treatment strategies (i.e., immediate</div>\n<div>\n upon enrollment vs. ART initiation when the participant has two consecutive</div>\n<div>\n measurements of a CD4+ cell count within or below the range of 200-250 cells/mm3,</div>\n<div>\n or develops an AIDS-defining illness).</div>\n<div>\n • Characterize and compare the patterns and rates of antiretroviral drug resistance of two</div>\n<div>\n antiretroviral treatment strategies.</div>\n<div>\n • Assess factors associated with adherence and compare the adherence rate of two</div>\n<div>\n antiretroviral treatment strategies.</div>\n<div>\n • Evaluate the usefulness of measures of virologic and immunologic efficacy, and measures</div>\n<div>\n to detect antiretroviral drug resistance.</div>\n<div>\n • Determine, characterize, and compare the rates of AIDS-defining illnesses, sexually</div>\n<div>\n transmitted diseases, opportunistic infections, and immune reconstitution syndromes, with</div>\n<div>\n regard to outcomes and survival as observed in different geographic settings and by</div>\n<div>\n antiretroviral treatment strategies.</div>\n<div>\n • Determine and characterize the rates of antiretroviral drug-associated toxicities observed</div>\n<div>\n in different geographic settings and by treatment strategies.</div>\n<div>\n • Evaluate the effectiveness of couples HIV counseling and characterize the patterns of</div>\n<div>\n sexual behavior in couples in both arms of the study.</div>\n<div>\n • Characterize and compare Quality-of-Life (QOL) indicators in different geographic</div>\n<div>\n settings and by antiretroviral treatment strategies.</div>\n<div>\n Study Sites:</div>\n<div>\n • Porto Alegre, Brazil</div>\n<div>\n • Rio de Janeiro, Brazil</div>\n<div>\n • Chennai, India</div>\n<div>\n • Pune, India</div>\n<div>\n • Blantyre, Malawi</div>\n<div>\n • Lilongwe, Malawi</div>\n<div>\n • Chiang Mai, Thailand</div>\n<div>\n • Boston, Massachusetts, United States of America</div>\n<div>\n • Harare, Zimbabwe</div>\n
      • study_title<div>\n A Randomized Trial to Evaluate the Effectiveness of Antiretroviral Therapy</div>\n<div>\n plus HIV Primary Care versus HIV Primary Care Alone to Prevent the Sexual</div>\n<div>\n Transmission of HIV-1 In Serodiscordant Couples</div>\n
      • laymans_summary(null)
      • short_title(null)
      • protocol_noECCT/09/06/02
      • version_no3.0
      • date_of_protocol20-11-2006
      • study_drugCombivir® [3TC/ZDV], efavirenz [EFV], atazanavir [ATV], nevirapine [NVP], tenofovir [TDF], lamivudine [3TC], didanosine [ddI-EC], stavudine [d4T], Aluvia® [LPV/r], and Truvada® [FTC/TDF]
      • disease_conditionHIV/AIDS
      • 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_nameCombivir® [3TC/ZDV], efavirenz, atazanavir, nevirapine, tenofovir, lamivudine, didanosine, stavudine, Lopinavir/ritonavir, and Emtricitabine/Tenofovir
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresseayuo@kemricdc.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_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantElizabeth Ayuo
      • declaration_date103-07-2013
      • declaration_principal_investigatorLisa A. Mills
      • declaration_date203-07-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<div>\n Couples are defined as sexual partners, same or opposite sex, who are married, have been</div>\n<div>\n living together, or consider each other a primary partner. They must have been together</div>\n<div>\n for a minimum of three months, and at the time of study enrollment expect to maintain</div>\n<div>\n their relationship for the duration of the study.</div>\n<div>\n Additional sexual partners of either the index case or their partner will not be eligible to</div>\n<div>\n enroll while the initial couple enrolled is being followed. Each partner of an HIV</div>\n<div>\n serodiscordant couple must meet the criteria presented below to be eligible for inclusion</div>\n<div>\n in this study.</div>\n<div>\n Whether individual HBV/HIV coinfected persons are enrolled into HPTN 052 will be left</div>\n<div>\n to the discretion of the site investigator.</div>\n<div>\n HPTN 052 Final Version 3.0, 20 November 2006 Page 45 of 173</div>\n<div>\n 3.1.1 Index Case</div>\n<div>\n • Positive HIV serology obtained within 60 days prior to enrollment</div>\n<div>\n Note: Confirmation of the initial positive or discordant test results (the initial test</div>\n<div>\n may be the results from two rapid tests) must use a test that is different than the</div>\n<div>\n one used for the initial assessment. Initially reactive rapid tests should be</div>\n<div>\n confirmed by Western blot or a plasma HIV-1 RNA. An initial ELISA result must</div>\n<div>\n be confirmed with another method such as Western blot or plasma HIV-1 RNA,</div>\n<div>\n but not by a repeat ELISA test.</div>\n<div>\n • Has a sexual partner (as defined above) who is not infected with HIV</div>\n<div>\n (documented by negative HIV serology), and who is willing to participate in the</div>\n<div>\n study.</div>\n<div>\n • Plans to maintain a sexual relationship with the person who is enrolled in the study</div>\n<div>\n with them.</div>\n<div>\n • Reports having sex (vaginal or anal) with partner at least 3 times in the last 3</div>\n<div>\n months.</div>\n<div>\n • If pregnant or breastfeeding during screening or at the time of enrollment, willing</div>\n<div>\n to be randomized to either arm of the study.</div>\n<div>\n Note: If a woman is in her first trimester during screening, the HPTN 052 CMC</div>\n<div>\n must be consulted prior to her enrollment.</div>\n<div>\n • The following conditions must be met for laboratory parameters within 60 days</div>\n<div>\n prior to enrollment:</div>\n<div>\n ô€‚ƒ CD4+ cell count of 350-550 cells/mm3</div>\n<div>\n ô€‚ƒ Hemoglobin > 7.5 g/dL (see Section 4.5.5.5 for information on anemia)</div>\n<div>\n ô€‚ƒ Platelet count > 50,000/µL.</div>\n<div>\n ô€‚ƒ AST (SGOT), ALT (SGPT), and alkaline phosphatase < 5 x ULN</div>\n<div>\n ô€‚ƒ Total bilirubin < 2.5 x ULN</div>\n<div>\n ô€‚ƒ Calculated creatinine clearance > 60 mL/min (use the Cockcroft and Gault</div>\n<div>\n method to calculate)</div>\n<div>\n ô€‚ƒ Absolute neutrophil count > 750 mm3 or 0.750 x 109/L (see Section 4.5.5.5</div>\n<div>\n for information on neutropenia)</div>\n<div>\n HPTN 052 Final Version 3.0, 20 November 2006 Page 46 of 173</div>\n<div>\n 3.1.2 Partner</div>\n<div>\n • Negative HIV serology within 14 days prior to enrollment.</div>\n<div>\n Note: If the initial test is two negative rapid tests, the participant will be considered</div>\n<div>\n HIV-negative and no further testing is required. If the initial test is a non-reactive</div>\n<div>\n EIA, the participant will be considered HIV-negative and no further testing is</div>\n<div>\n required.</div>\n<div>\n • Has a sexual partner infected with HIV who is willing to participate in the study.</div>\n<div>\n • Plans to maintain a sexual relationship with the person who is enrolled in the study</div>\n<div>\n with them.</div>\n<div>\n • Reports having sex (vaginal or anal) with partner at least 3 times in the last 3</div>\n<div>\n months.</div>\n<div>\n 3.1.3 Both Index Case and Partner</div>\n<div>\n • Men and women age > 18 years.</div>\n<div>\n • Willing to disclose HIV test results to partner.</div>\n<div>\n • Not intending to relocate out of the area for the duration of study participation and</div>\n<div>\n does not have a job or other obligations that may require long absences from the</div>\n<div>\n area.</div>\n
      • principal_exclusion_criteria<div>\n Index Case</div>\n<div>\n • Current or previous AIDS-defining illness (as defined in Appendix III). (Note:</div>\n<div>\n active TB, as defined by the ACTG Appendix 60 - Diagnoses Appendix, is an</div>\n<div>\n exclusion, as well as currently being on intensive phase of TB treatment, but</div>\n<div>\n previously treated cases of pulmonary TB may be waived at the discretion of the</div>\n<div>\n study clinician.)</div>\n<div>\n • Current or previous use of any ART drugs (exceptions will be outlined in the SSP</div>\n<div>\n Manual. For example, previous short-term use of ART for prevention of perinatal</div>\n<div>\n transmission will be waived as an exclusion).</div>\n<div>\n • Documented or suspected acute hepatitis within 30 days prior to enrollment,</div>\n<div>\n irrespective of AST (SGOT) and ALT (SGPT) values.</div>\n<div>\n • Acute therapy for serious medical illnesses, in the opinion of the site investigator,</div>\n<div>\n within 14 days prior to enrollment. Candidates with chronic, acute, or recurrent</div>\n<div>\n infections that are serious, in the opinion of the site investigator, who must</div>\n<div>\n HPTN 052 Final Version 3.0, 20 November 2006 Page 47 of 173</div>\n<div>\n continue with chronic (maintenance) therapy (e.g., TB), must have completed at</div>\n<div>\n least 14 days of therapy prior to study entry and be clinically stable.</div>\n<div>\n • Radiation therapy or systemic chemotherapy within 45 days prior to enrollment.</div>\n<div>\n NOTE: Anticipated need for systemic chemotherapy while on study is not</div>\n<div>\n permitted.</div>\n<div>\n • Any immunomodulator or other investigational therapy within 30 days prior to</div>\n<div>\n enrollment.</div>\n<div>\n • Active drug or alcohol use or dependence that, in the opinion of the site</div>\n<div>\n investigator, would interfere with adherence to study requirements.</div>\n<div>\n • Vomiting or inability to swallow medications due to an active, pre-existing</div>\n<div>\n condition that prevents adequate swallowing and absorption of study medication.</div>\n<div>\n • Need for a prohibited medication listed in Section 4.3.2.</div>\n<div>\n • Allergy/sensitivity to any study drugs or their formulations.</div>\n<div>\n 3.2.2 Both Index Case and Partner</div>\n<div>\n • Reports a history of injection drug use within the last five years.</div>\n<div>\n • Previous and/or current participant in an HIV vaccine study.</div>\n<div>\n • Any condition that, in the opinion of the study staff, would make participation in</div>\n<div>\n the study unsafe, complicate interpretation of study outcome data, or</div>\n<div>\n otherwise interfere with achieving the study objectives.</div>\n<div>\n • Incarceration in a correctional facility, prison, or jail; and involuntary</div>\n<div>\n incarceration in a medical facility for psychiatric or physical (e.g. infectious</div>\n<div>\n disease) illness.</div>\n<div>\n 3.3 Screening and Enrollment Procedures</div>\n<div>\n Identification of HIV serodiscordant couples will vary across sites and within an</div>\n<div>\n individual site (e.g. couples already identified as HIV serodiscordant and referred to the</div>\n<div>\n site by a local voluntary counseling and testing (VCT) center, referral of HIV-infected</div>\n<div>\n individuals from local STD/HIV clinics or other research protocols, or referral of</div>\n<div>\n HIV-uninfected individuals to the study site). Thus, it will be the responsibility of each</div>\n<div>\n participating site to determine the best screening methods for their locale, and will likely be</div>\n<div>\n dictated on a case-by-case basis.</div>\n<div>\n The protocol will not define an algorithm for HIV screening for study eligibility. Study</div>\n<div>\n sites will be responsible for developing a local SOP for this study component; however,</div>\n<div>\n the HPTN Central Laboratory should approve the screening algorithm employed. In</div>\n<div>\n HPTN 052 Final Version 3.0, 20 November 2006 Page 48 of 173</div>\n<div>\n addition, previous HIV screening with positive test results will be accepted as eligibility</div>\n<div>\n for this study only if:</div>\n<div>\n • the testing occurred within the dictated timeframe for this study (within 60 days)</div>\n<div>\n • the testing was performed during a time that the site had HPTN Central</div>\n<div>\n Laboratory certificate of accreditation</div>\n<div>\n • the testing has appropriate documentation (i.e. documentation is consistent with</div>\n<div>\n what would otherwise be required for research purposes such as test date, test</div>\n<div>\n results, and identification of the testing laboratory)</div>\n
      • primary_end_points<p>\n Seroconversion of the index participant</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • 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_other1
      • trial_other_specifyInvestigational New drug
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Site Principal Investigator (PI):               Lisa A. Mills, MD, MS</p>\n<p>\n Co-investigators:                                   Kayla Laserson,</p>\n<p>\n                                                                     Charles LeBaron, MD</p>\n<p style=\"margin-left:2.5in;\">\n Debra Gust PhD;</p>\n<p style=\"margin-left:2.5in;\">\n Robert T Chen, MD, MA</p>\n<p style=\"margin-left:2.5in;\">\n Clement Zeh, BSc</p>\n<p style=\"margin-left:2.5in;\">\n Victor Akelo, MD</p>\n<p style=\"margin-left:2.5in;\">\n Kevin Cain, MD, MPH</p>\n<p style=\"margin-left:2.5in;\">\n Videlis Nduba, MD, MPH</p>\n<p style=\"margin-left:2.5in;\">\n Ephantus Wanjema, MD</p>\n<p style=\"margin-left:2.5in;\">\n Richard Lando, DCM</p>\n<p style=\"margin-left:2.5in;\">\n Beatrice Nyagol, DCM</p>\n<p>\n Study Medical Officer:                           Victor Akelo, MD</p>\n<p>\n Study Coordinator:                                Arthur Ogendo BA</p>\n<p>\n Study Pharmacist:                                 Victor Mudhune, B. Pharm</p>\n<p>\n Laboratory Director:                              Clement Zeh, BSc</p>\n<p>\n Data Section Chief:                               Richard Ndivo, BSc</p>\n<p>\n Regulatory Officer:                                Elizabeth Ayuo, BA</p>\n<p>\n Behavioral Scientist:                              Mary Nyikuri, MA</p>\n<p>\n HIV Research Branch Chief:                   Lisa A. Mills, MD, MS</p>\n<p>\n HIV Research Branch Deputy:                Ray Goldstine, Pharm D</p>\n<p style=\"margin-left:2.5in;\">\n Kevin Cain, MD, MPH</p>\n<p style=\"margin-left:2.5in;\">\n Videlis Nduba, MD, MPH</p>\n<p style=\"margin-left:2.5in;\">\n Ephantus Wanjema, MD</p>\n<p style=\"margin-left:2.5in;\">\n Richard Lando, DCM</p>\n<p style=\"margin-left:2.5in;\">\n Beatrice Nyagol, DCM</p>\n<p>\n Study Medical Officer:                           Victor Akelo, MD</p>\n<p>\n Study Coordinator:                                Arthur Ogendo BA</p>\n<p>\n Study Pharmacist:                                 Victor Mudhune, B. Pharm</p>\n<p>\n Laboratory Director:                              Clement Zeh, BSc</p>\n<p>\n Data Section Chief:                               Richard Ndivo, BSc</p>\n<p>\n Regulatory Officer:                                Elizabeth Ayuo, BA</p>\n<p>\n Behavioral Scientist:                              Mary Nyikuri, MA</p>\n<p>\n HIV Research Branch Chief:                   Lisa A. Mills, MD, MS</p>\n<p>\n HIV Research Branch Deputy:                Ray Goldstine, Pharm D</p>\n
      • other_details_explanation<p>\n the study was conducted in the US in its early enrollment., Site: Boston Massachusettes</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI Ethics Review Committee and Scientific Steering Committe - 06MAY2013</p>\n<p>\n CDC Ethics Review Committe - 12FEB2013</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration6 years
      • 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_comparatorPrimary care only
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKisumu, Kenya
      • single_site_physical_addressOngielo Health Centre, off Luanda K\'otieno Road, Asembo.
      • single_site_contact_personDr. Lisa Mills
      • single_site_telephone+254572022929
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states1750
      • number_of_sites
      • multi_country_listPorto Alegre, Brazil\n• Rio de Janeiro, Brazil\n• Chennai, India\n• Pune, India\n• Blantyre, Malawi\n• Lilongwe, Malawi\n• Chiang Mai, Thailand\n• Boston, Massachusetts, United States of America\n• Harare, Zimbabwe
      • data_monitoring_committeeYes
      • total_enrolment_per_site60 couples
      • total_participants_worldwide1750 couples
      • 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_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameLisa
      • investigator1_middle_nameAnn
      • investigator1_family_nameMills
      • investigator1_qualificationMD
      • investigator1_professional_address1578-40100, Kisumu
      • investigator1_telephone+254-57-2022929
      • investigator1_emailLmills@ke.cdc.gov
      • organisations_transferred_Yes
      • number_participants100 couples
      • notification<p>\n NONE</p>\n
      • approval_date05-07-2012
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-07-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n 1.    HPTN 052 is the first randomized clinical trial to show that treating HIV-infected individuals with antiretroviral therapy (ART) early in their HIV infection (CD4 cell count 350-550/mm³) reduces the risk of sexual transmission of HIV to their uninfected partners, and also provides a clear clinical benefit to the HIV-infected individual; notably, early ART leads to a longer duration of time without diseases such as tuberculosis and other targeted clinical events.</p>\n<p>\n  </p>\n<p>\n 2.    ART reduced HIV acquisition by 93% in the entire study, which is similar to the 96% reduction reported in the interim analysis in 2011. </p>\n<p>\n  </p>\n<p>\n 3.    Virologically-linked partner infections were not observed when the index participant was stably suppressed on ART.</p>\n<p>\n  </p>\n<p>\n 4.    ART, when taken until viral suppression is achieved and sustained, is a highly effective, durable intervention for HIV prevention.</p>\n<p>\n  </p>\n<p>\n HPTN 052 was funded by the funded by the National Institute for Allergy and Infectious Diseases (NIAID) at the US National Institutes of Health (NIH</p>\n
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2015-10-28 16:56:58
      • created2013-05-31 14:03:38
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id98
        • application_id141
        • given_nameLisa
        • middle_nameAnn
        • family_nameMills
        • qualificationMD
        • professional_address1578-40100 Kisumu
        • telephone+254-57-2022929
        • emailvmudhune@ke.cdc.gov
        • created2013-06-19 15:57:10
        • modified2013-07-03 12:56:14
    • SiteDetail(array)
      • 0(array)
        • id125
        • application_id141
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2013-06-19 15:57:10
        • modified2013-07-03 12:56:14
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id79
        • application_id141
        • sponsorDivision of AIDS, U.S. National Institute of Allergy and Infectious Diseases
        • sponsor_type(null)
        • contact_personBola Adedeji
        • addressInternational Health Programs Specialist Office of Clinical Site Oversight (OCSO) OD/DAIDS/NIAID/NIH/DHHS 6700B Rockledge Drive, Room 5111 MSC 7624 Bethesda, MD 20892-7624 express mail: Bethesda, MD 20817
        • telephone_number(301) 496-7122
        • fax_number(301) 480-7675
        • cell_number(301) 496-7122
        • email_addressBAdedeji@niaid.nih.gov
        • created2013-06-19 15:57:10
        • modified2013-07-03 12:56:14
  • 3(array)
    • Application(array)
      • id446
      • user_id77
      • trial_status_id4
      • abstract_of_study<div>\n ABSTRACT</div>\n<div>\n The study titled “A Randomized Evaluation of Antiretroviral Therapy Alone or with</div>\n<div>\n Delayed Chemotherapy versus Antiretroviral Therapy with Immediate Adjunctive</div>\n<div>\n Chemotherapy for Treatment of Limited Stage AIDS-KS in Resource-Limited</div>\n<div>\n Settings (REACT-KS)” is a phase III, open-label, prospective, randomized study</div>\n<div>\n stratified by CD4+ lymphocyte cell count and antiretroviral therapy (ART) history.</div>\n<div>\n This study will compare ART alone, or with delayed chemotherapy to ART with</div>\n<div>\n immediate adjunctive chemotherapy for initial treatment of limited stage AIDSrelated</div>\n<div>\n Kaposi’s sarcoma (AIDS-KS), in chemotherapy and radiation treatment naïve</div>\n<div>\n HIV-1 infected participants who are currently not receiving ART.</div>\n<div>\n The target population includes males and females  18 years of age with the</div>\n<div>\n following characteristics: documentation of HIV-1 infection, biopsy diagnostic of KS,</div>\n<div>\n current limited stage KS (T0 and some T1 stage KS), systemic chemotherapy for KS</div>\n<div>\n and radiation treatment naïve, and currently not receiving ART. A total of 468</div>\n<div>\n participants (234 in each Arm of Step 1) will be enrolled across all sites, with the</div>\n<div>\n KEMRI/CDC site proposing to contribute about 50 participants, and could be</div>\n<div>\n more given enrollment across sites is competitive. Randomization will be stratified</div>\n<div>\n by screening peripheral blood CD4+ lymphocyte cell count (< 200 or  200</div>\n<div>\n cells/mm³) and ART history (naïve or experienced). At study entry participants will</div>\n<div>\n be randomized 1:1 to one of the following arms in Step 1: Arm 1A, Co-formulated</div>\n<div>\n efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) and arm 1B,</div>\n<div>\n co-formulated EFV/FTC/TDF and ET. In Step 2, at the discretion of the site</div>\n<div>\n investigator, after confirmation of disease progression by the IERC (Independent</div>\n<div>\n Endpoint Review Committee), participants who experience KS progression in Arm</div>\n<div>\n 1A will receive ET in addition to co-formulated EFV/FTC/TDF. In step 3,</div>\n<div>\n participants who received ET will remain on the study for 240 weeks (96 weeks +</div>\n<div>\n 144 weeks of follow-up for safety). Participants never receiving etoposide (VePesid®,</div>\n<div>\n ET) will be followed up for 96 weeks.</div>\n<div>\n The primary endpoint incorporates KS tumor response, KS progression, loss to</div>\n<div>\n follow-up, and initiation of new chemotherapy agent other than ET, as an ordinal,</div>\n<div>\n categorical outcome i.e. failure, stable and respose. The main interest of the study is</div>\n<div>\n the outcome at 48 weeks after the treatment initiation. KS follow-up to 96 weeks of</div>\n<div>\n SSA (Protocol No ACTG A5264), Version 1.1 Page 5 of 96</div>\n<div>\n the study will allow assessments of study arm differences beyond 48 weeks. The</div>\n<div>\n primary analysis will be conducted when the data on 96-week follow-up are</div>\n<div>\n completed on all the study participants (at Step 2 completion).</div>\n
      • study_title<div>\n A Randomized Evaluation of Antiretroviral Therapy Alone or with Delayed Chemotherapy</div>\n<div>\n versus Antiretroviral Therapy with Immediate Adjunctive Chemotherapy for Treatment of</div>\n<div>\n Limited Stage AIDS-KS in Resource-Limited Settings (REACT-KS)</div>\n
      • laymans_summary(null)
      • short_titleA5264
      • protocol_noECCT/15/11/01
      • version_noversion 1.0
      • date_of_protocol04-08-2010
      • study_drugStudy provided study products are etoposide (VePesid®), FTC/TDF (Truvada®), EFV (Stocrin®), and EFV/FTC/TDF (Atripla®). Study treatment is considered etoposide (VePesid®) chemotherapy product plus, study provided ART or an approved, non-study provide
      • disease_conditionAIDS KS
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid1
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameVP-16, toposar, vepeside
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresseayuo@kemricdc.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_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr. Victor Otieno Mudhune
      • declaration_date105-11-2015
      • declaration_principal_investigatorDr. Victor Otieno Mudhune - A5264 Study PI
      • declaration_date205-11-2015
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<div>\n HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme</div>\n<div>\n or chemiluminescence immunoassay (E/CIA) test kit at any time prior to</div>\n<div>\n study entry and confirmed by a licensed Western blot or a second antibody</div>\n<div>\n test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1</div>\n<div>\n antigen, plasma HIV-1 RNA viral load.</div>\n<div>\n SSA (Protocol No ACTG A5264), Version 1.1 Page 11 of 96</div>\n<div>\n b. Biopsy diagnostic of KS at any time prior to study entry.</div>\n<div>\n c. Current limited stage KS using the ACTG criteria. (Limited stage KS is</div>\n<div>\n defined as stage T0 and some presentations of stage T1 KS).</div>\n<div>\n d. A minimum of 5 cutaneous marker lesions</div>\n<div>\n e. The following laboratory values obtained within 14 days prior to study entry:</div>\n<div>\n ï‚· Absolute neutrophil count (ANC)  1,000 cells/mm3.</div>\n<div>\n ï‚· Hemoglobin  9.0 g/dL.</div>\n<div>\n ï‚· Platelet count  100,000/mm3.</div>\n<div>\n ï‚· Calculated creatinine clearance of ≥ 60 mL/min using the Cockroft-</div>\n<div>\n Gault formula (defined in the study protocol).</div>\n<div>\n ï‚· AST (SGOT), ALT (SGPT), and alkaline phosphatase < 5 ï‚´ ULN.</div>\n<div>\n ï‚· Total bilirubin of < 1.5 X ULN.</div>\n<div>\n f. Female participants of reproductive potential must have a negative serum or</div>\n<div>\n urine pregnancy test with a sensitivity of 15-25mlIU/ml performed within 7</div>\n<div>\n days prior to study entry.</div>\n<div>\n g. All participants must agree not to participate in a conception process (e.g.,</div>\n<div>\n active attempt to become pregnant or to impregnate, donate sperm, in vitro</div>\n<div>\n fertilization).</div>\n<div>\n h. Female participants who are participating in sexual activity that could lead to</div>\n<div>\n pregnancy must agree to use a combination of TWO of the following</div>\n<div>\n methods:</div>\n<div>\n ï‚· Condoms (male or female) with or without a spermicidal agent.</div>\n<div>\n ï‚· Diaphragm or cervical cap with spermicide</div>\n<div>\n ï‚· IUD</div>\n<div>\n ï‚· Hormonal-based contraception. This must be used while receiving ET,</div>\n<div>\n efavirenz, rifampicin, or other rifamycin, and for 12 weeks after stopping</div>\n<div>\n these drugs.</div>\n<div>\n i. Ability to swallow oral medications.</div>\n<div>\n j. Men and women, age  18 years.</div>\n<div>\n SSA (Protocol No ACTG A5264), Version 1.1 Page 12 of 96</div>\n<div>\n k. Karnofsky performance score  60 within 30 days prior to entry.</div>\n<div>\n l. Ability and willingness of participant or legal guardian/representative to</div>\n<div>\n provide informed consent.</div>\n<div>\n m. Peripheral blood CD4+ lymphocyte cell count obtained within 30 days prior</div>\n<div>\n to study entry at a DAIDS-approved laboratory.</div>\n<div>\n n. For treatment-experienced patients, the availability of an ART regimen that</div>\n<div>\n includes at least two ART drugs that in the opinion of the site investigator are</div>\n<div>\n expected to have activity based on historical genotypic testing (if available)</div>\n<div>\n and treatment history.</div>\n<div>\n o. For participants who are to receive ART other than EFV/TDF/FTC, the</div>\n<div>\n availability of those ART components.</div>\n<div>\n Step 2 inclusion criteria include:</div>\n<div>\n a. KS progression after a complete or partial response as defined in sections 7.1</div>\n<div>\n of the protocol, while on Step 1 Arm 1A, between weeks 8 and 80.</div>\n<div>\n b. Need for ET for treatment of KS progression, in the opinion of the site</div>\n<div>\n investigator, after confirmation of KS progression by the IERC.</div>\n<div>\n c. Willingness to receive ET for treatment of KS progression.</div>\n<div>\n d. Female participants of reproductive potential must have a negative serum or</div>\n<div>\n urine pregnancy test with a sensitivity of 15-25mlIU/ml performed within 7</div>\n<div>\n days prior to initiating ET.</div>\n<div>\n e. Karnofsky Performance Score ≥ 50.</div>\n<div>\n f. The following laboratory values obtained within 14 days prior to Step 2</div>\n<div>\n entry:</div>\n<div>\n  ANC  1,000 cells/mm3.</div>\n<div>\n  Hemoglobin  9.0 g/dL.</div>\n<div>\n  Platelet count  100,000/mm3.</div>\n<div>\n  Estimated creatinine clearance of ≥ 60 mL/min using the Cockroft-Gault</div>\n<div>\n formula as indicated in the protocol.</div>\n<div>\n SSA (Protocol No ACTG A5264), Version 1.1 Page 13 of 96</div>\n<div>\n  AST (SGOT), ALT (SGPT), and alkaline phosphatase < 5 ï‚´ ULN.</div>\n<div>\n  Total bilirubin of < 1.5 X ULN.</div>\n<div>\n g. Ability to swallow oral medications.</div>\n<div>\n h. All participants must agree not to participate in a conception process (e.g.,</div>\n<div>\n active attempt to become pregnant or to impregnate, donate sperm, in vitro</div>\n<div>\n fertilization).</div>\n<div>\n i. Female participants who are participating in sexual activity that could lead to</div>\n<div>\n pregnancy must agree to use a combination of TWO of the following</div>\n<div>\n methods:</div>\n<div>\n ï‚· Condoms (male or female) with or without a spermicidal agent.</div>\n<div>\n ï‚· Diaphragm or cervical cap with spermicide</div>\n<div>\n ï‚· IUD</div>\n<div>\n ï‚· Hormonal-based contraception. This must be used while receiving ET,</div>\n<div>\n EFV, RIF, or other rifamycin, and for 12 weeks after stopping these</div>\n<div>\n drugs.</div>\n<div>\n Step 3 inclusion criteria include:</div>\n<div>\n a. Received at least one dose of ET (Arm 1B or Arm 2A).</div>\n<div>\n 5.4. Exclusion Criteria</div>\n<div>\n Step 1 exclusion criteria:</div>\n<div>\n a. Any manifestation of KS which, in the opinion of the site investigator,</div>\n<div>\n requires immediate chemotherapy.</div>\n<div>\n b. Receipt of ART within 6 months prior to study entry.</div>\n<div>\n c. Biopsy proven KS during previous ART.</div>\n<div>\n d. Breastfeeding.</div>\n<div>\n e. Allergy/sensitivity to any study drug or its formulations.</div>\n<div>\n f. Any prior systemic anti-neoplastic treatment for KS (including</div>\n<div>\n chemotherapy, biological therapy, immunotherapy or investigational</div>\n<div>\n therapy).</div>\n<div>\n SSA (Protocol No ACTG A5264), Version 1.1 Page 14 of 96</div>\n<div>\n g. Any prior local treatment of cutaneous marker lesions unless there was</div>\n<div>\n evidence of a clear-cut progression of the lesion.</div>\n<div>\n h. Receipt of any investigational therapy within 30 days prior to study entry.</div>\n<div>\n i. Current or anticipated receipt of any of the prohibited medications indicated</div>\n<div>\n in the protocol under section 5.4.2.</div>\n<div>\n j. In the opinion of the site investigator, any psychological or social condition,</div>\n<div>\n or addictive disorder that would preclude compliance with the protocol.</div>\n<div>\n k. Current chronic, acute, or recurrent infections that are serious, in the opinion</div>\n<div>\n of the site investigator, for which the participant has not completed at least 14</div>\n<div>\n days of therapy prior to study entry and/or is not clinically stable.</div>\n
      • principal_exclusion_criteria<div>\n Exclusion Criteria</div>\n<div>\n Step 1 exclusion criteria:</div>\n<div>\n a. Any manifestation of KS which, in the opinion of the site investigator,</div>\n<div>\n requires immediate chemotherapy.</div>\n<div>\n b. Receipt of ART within 6 months prior to study entry.</div>\n<div>\n c. Biopsy proven KS during previous ART.</div>\n<div>\n d. Breastfeeding.</div>\n<div>\n e. Allergy/sensitivity to any study drug or its formulations.</div>\n<div>\n f. Any prior systemic anti-neoplastic treatment for KS (including</div>\n<div>\n chemotherapy, biological therapy, immunotherapy or investigational</div>\n<div>\n therapy).</div>\n<div>\n SSA (Protocol No ACTG A5264), Version 1.1 Page 14 of 96</div>\n<div>\n g. Any prior local treatment of cutaneous marker lesions unless there was</div>\n<div>\n evidence of a clear-cut progression of the lesion.</div>\n<div>\n h. Receipt of any investigational therapy within 30 days prior to study entry.</div>\n<div>\n i. Current or anticipated receipt of any of the prohibited medications indicated</div>\n<div>\n in the protocol under section 5.4.2.</div>\n<div>\n j. In the opinion of the site investigator, any psychological or social condition,</div>\n<div>\n or addictive disorder that would preclude compliance with the protocol.</div>\n<div>\n k. Current chronic, acute, or recurrent infections that are serious, in the opinion</div>\n<div>\n of the site investigator, for which the participant has not completed at least 14</div>\n<div>\n days of therapy prior to study entry and/or is not clinically stable.</div>\n<div>\n Step 2 exclusion criteria:</div>\n<div>\n a. Current chronic, acute, or recurrent infections that are serious, in the opinion</div>\n<div>\n of the site investigator, for which the participant has not completed at least 14</div>\n<div>\n days of therapy prior to initiating ET and/or is not clinically stable.</div>\n<div>\n b. Current or anticipated receipt of any of the prohibited medications indicated</div>\n<div>\n in the protocol under section 5.4.2.</div>\n<div>\n c. Breastfeeding.</div>\n
      • primary_end_points<div>\n Rationale for Primary Endpoint</div>\n<div>\n The primary endpoint will be a composite endpoint of KS tumor response, KS</div>\n<div>\n progression, initiation of a new chemotherapy agent other than ET, and lost to follow-up</div>\n<div>\n (including death). The outcome variable is an ordinal response. The worst outcome is E1</div>\n<div>\n (Failure): disease progression as evidenced by tumor progression at week 48 compared</div>\n<div>\n to baseline or need for initiation of a new chemotherapy regimen other than ET, by week</div>\n<div>\n 48. In addition, participants who die or are lost-to-follow-up will be included in this group.</div>\n<div>\n The middle outcome is E2 participants with stable KS (i.e., no improvement and no</div>\n<div>\n progression) at week 48. The best outcome is E3 (Response) participants who have</div>\n<div>\n demonstrated regression or resolution of KS at week 48.</div>\n<div>\n A 48-week endpoint was chosen to allow a period off chemotherapy for most participants</div>\n<div>\n prior to the primary endpoint to allow for the possibility of worsening disease after</div>\n<div>\n discontinuing chemotherapy. It also allows ample time for participants on ART alone to</div>\n<div>\n mount an immune response against KSHV sufficient to cause tumor regression. The</div>\n<div>\n ordinal endpoint was chosen because having stable KS is clearly better than having KS</div>\n<div>\n progression, but cannot be viewed as a complete treatment success.</div>\n<div>\n 30 A5264/AMC067</div>\n<div>\n FINAL Version 1.0</div>\n<div>\n 08/04/10</div>\n<div>\n Prospective studies on the response of T0 KS cases treated with ART alone in the</div>\n<div>\n resource-limited setting are not available. Based on input from A5264/AMC067 site</div>\n<div>\n investigators we estimate that 30% of participants with T0 KS treated with ART alone or</div>\n<div>\n with delayed initiation of ET will have KS tumor progression compared to baseline at</div>\n<div>\n week 48 and 70% will not [3]. Based on observations from KS clinical care in Uganda</div>\n<div>\n (Jackson Orem, personal communication), we estimate that in participants treated with</div>\n<div>\n ART alone or those who have delayed initiation of ET, 40% will be stable and 30% will</div>\n<div>\n have at least partial response at week 48.</div>\n<div>\n Rationale for Secondary Endpoints</div>\n<div>\n Even though the planned primary endpoint will analyze treatment response at 48 weeks,</div>\n<div>\n A5264/AMC067 is designed to obtain follow-up data to 96 weeks in each participant.</div>\n<div>\n Follow-up to 96 weeks will allow assessment of the durability of treatment response and</div>\n<div>\n will provide assessment of delayed treatment responses that might occur between</div>\n<div>\n weeks 48 and 96. Individuals randomized to Arm 1A (ART only) may experience KS</div>\n<div>\n progression at a variable time after starting protocol treatment and thus may then have</div>\n<div>\n ET added to their regimen at variable times. Participants who initiate ET may then be</div>\n<div>\n treated with up to eight 2-week cycles of chemotherapy. Following participants for 96</div>\n<div>\n weeks will allow adequate time to evaluate the response to chemotherapy in individuals</div>\n<div>\n in whom such therapy is initiated after 24 or more weeks of ART alone and will permit a</div>\n<div>\n more robust evaluation of response duration in these participants.</div>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • 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 Dr. Elisha Okeyo- MD</p>\n<p>\n Dr. Joan Cain - Oncologist</p>\n<p>\n Dr. Esther Mumbi Makanga- MD</p>\n<p>\n Dr. Victor Mudhune - Pharmacist</p>\n<p>\n Dr. Kevin P. Cain - MD</p>\n<p>\n Dr. Victor Akelo MD</p>\n<p>\n Dr. Kenneth Masamaro - MD</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n it is also conducted in the USA</p>\n
      • other_details_regulatory_notapproved<p>\n KEMRI Scientific Ethics Review Unit 9 SERU) - approval 28th Sept 2015</p>\n
      • other_details_regulatory_approved<p>\n KEMRI - for WRP KERICHO</p>\n<p>\n MOI UNIVERSITY - AMPATH ELDORET</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration5 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorEFV/FTC/TDF and ET
      • design_controlled_other_medicinalYes
      • 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_countriesYes
      • multiple_member_states12
      • number_of_sites2 more
      • multi_country_listWestern Cape-South Africa, Rio de Janeiro-Brazil,\nBlantyre-Malawi, Durban-South Africa, Kampala-Uganda, Kericho-Kenya,\nLilongwe-Malawi, Harare-Zimbabwe, Eldoret-Kenya, Lima-Peru, Johanesburg-\nSouth Africa)
      • data_monitoring_committeeYes
      • total_enrolment_per_site50
      • total_participants_worldwide468 participants (234 in each Arm of Step 1)
      • 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_female1
      • gender_male1
      • subjects_healthyNo
      • 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. Elisha
      • investigator1_middle_nameOchieng
      • investigator1_family_nameOkeyo
      • investigator1_qualificationMD
      • investigator1_professional_addressKEMRI CDC - 1578 Kisumu
      • investigator1_telephone+254721410654
      • investigator1_emaileokeyo@kemricdc.org
      • organisations_transferred_No
      • number_participants50
      • notification
      • approval_date05-05-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted10-11-2015
      • 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)
      • modified2016-05-23 10:08:52
      • created2015-11-05 11:15:54
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id297
        • application_id446
        • given_nameDr. Victor
        • middle_nameOtieno
        • family_nameMudhune
        • qualificationBpharm, MPH
        • professional_addressKEMRICDC 1578 Kisumu
        • telephone0722687430
        • emailvmudhune@kemricdc.org
        • created2015-11-05 14:54:01
        • modified2015-11-10 12:09:56
    • SiteDetail(array)
      • 0(array)
        • id356
        • application_id446
        • county_id42
        • site_nameKEMRI CDC
        • physical_addressKEMRI CDC CLINICAL RESEARCH CENTRE
        • contact_details1578, KISUMU 40100
        • contact_personDR. VICTOR MUDHUNE
        • site_capacity(null)
        • misc(null)
        • created2015-11-05 14:54:01
        • modified2015-11-10 12:09:56
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id232
        • application_id446
        • sponsorThe National Institute of Allergy and Infectious Diseases (NIAID) National Cancer Institute (NCI) National Institute of Dental Craniofacial Research (NIDCR)
        • sponsor_type(null)
        • contact_personThomas B. Campbell, M.D.
        • addressUniversity of Colorado Denver Box B-168 12700 E. 19th Avenue Aurora, CO 80045
        • telephone_numberPhone: (303) 724-4929
        • fax_number
        • cell_numberPhone: (303) 724-4929
        • email_addressThomas.Campbell@ucdenver.edu
        • created2015-11-05 14:54:01
        • modified2015-11-10 12:09:56
  • 4(array)
    • Application(array)
      • id1300
      • user_id622
      • trial_status_id6
      • abstract_of_study<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"color: rgb(0, 0, 0);\"><strong>PROTOCOL NUMBER</strong>: </span><span style=\"color: rgb(34, 34, 34);\">BO42451</span></span></span></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"color: rgb(0, 0, 0);\"><strong>STUDY NAME</strong>: Crosswalk c</span></span></span></div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"color: rgb(0, 0, 0);\"><strong>VERSION NUMBER</strong>: </span>2 (Africa)</span></span></div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"color: rgb(0, 0, 0);\"><strong>TEST COMPOUND(S)</strong>: </span>Crovalimab (RO7112689)</span></span></div>\n <div>\n  </div>\n <div>\n  </div>\n</div>\n<div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">This randomized, multicenter, placebo-controlled, double-blinded Phase IIa study is designed to evaluate the efficacy, safety, and pharmacokinetics of crovalimab compared with placebo as adjunct therapy in the prevention of VOE in patients with SCD. The study will enroll approximately 90 patients at approximately 30 sites globally. The screening period of the study will be up to 28 days in length. Patients who do not meet the criteria for participation in this study (screen failure) may qualify for two rescreening opportunities (for a total of three screenings per patient) at the investigator’s discretion.</span></span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Eligible patients will be randomized 1:1 to receive either crovalimab or placebo in addition to their current SCD therapy. Patients in both treatment arms will receive standard treatment for SCD as guided by the treating physician and/or institutional guidelines, including but not limited to treatments currently approved for SCD within each country participating in this study (e.g., hydroxyurea, L-glutamine, crizanlizumab, or voxelotor), pain management treatment (e.g., opioid analgesics, NSAIDs), hydration, oxygen, and other best supportive care (BSC).</span></span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Stratification factors at randomization are:</span></span></div>\n<div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">- Number of VOEs in the 12 months prior to enrollment (less than 4 vs. more than or equal to 4 VOEs)</span></span></div>\n<div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">- Use of concurrent SCD-directed therapy in any combination (e.g., hydroxyurea, L-glutamine, crizanlizumab, or voxelotor) (yes vs. no)</span></span></div>\n<div>\n  </div>\n<div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The primary analysis will be performed when all patients have either completed 48 weeks of the study treatment (refers to crovalimab or placebo) or have discontinued from the study, whichever occurs first.</span></span></div>\n <div>\n  </div>\n <div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">An initial crovalimab (or matching placebo) intravenous (IV) loading dose will be administered on Week 1 Day 1 followed by 4 weekly subcutaneous (SC) doses of the study treatment on Week 1 Day 2, then on Weeks 2, 3, and 4. Maintenance dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter, for a total of 48 weeks of treatment. All patients will receive the study treatment according to a weight-based tiered dosing schedule. Study treatment dosing will continue per protocol schedule during any medical facility or home VOE occurring on treatment.</span></span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">For patients who discontinue from study treatment, a safety follow-up visit will be conducted at 24 weeks after the last dose of study treatment, and a safety follow-up telephone call will be conducted at 46 weeks after the last dose of study treatment.</span></span></div>\n </div>\n <div>\n  </div>\n <div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><strong>NUMBER OF PATIENTS</strong></span></span></div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Approximately 90 patients with SCD will be randomized in this study.</span></span></div>\n </div>\n <div>\n  </div>\n <div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><strong>END OF STUDY</strong></span></span></div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The end of this study is defined as the date when the last patient, last visit, occurs, which is defined as completion of 48 weeks of the study treatment, followed by the end of safety follow-up period of 46 weeks. The end of the study is expected to occur approximately 2 years  after the last patient is enrolled. In addition, the study treatment may be discontinued, the patient may discontinue from the study, or the Sponsor may decide to terminate the study or discontinue a site at any time.</span></span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><strong>LENGTH OF STUDY</strong></span></span></div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The total length of the study, from screening of the first patient to the end of the study, is expected to be approximately 3.5 years.</span></span></div>\n </div>\n</div>\n<p>\n  </p>\n
      • study_title<div>\n A RANDOMIZED DOUBLE-BLIND PHASE IIA STUDY EVALUATING THE EFFICACY, SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF CROVALIMAB AS ADJUNCT TREATMENT IN PREVENTION OF VASO-OCCLUSIVE EPISODES (VOE) IN SICKLE CELL DISEASE (SCD) (CROSSWALK-c)</div>\n
      • laymans_summary<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"color: rgb(0, 0, 0);\">This study is designed to evaluate the efficacy, safety and pharmacokinetics of crovalimab compared with placebo as adjunct therapy in the prevention of VOEs in participants with SCD.</span></span></span></p>\n<div>\n This randomized, multicenter, placebo-controlled, double-blinded Phase IIa study is designed to evaluate the efficacy, safety, and pharmacokinetics of crovalimab compared with placebo as adjunct therapy in the prevention of VOE in patients with SCD. The study will enroll approximately 90 patients at approximately 30 sites globally. The screening period of the study will be up to 28 days in length. Patients who do not meet the criteria for participation in this study (screen failure) may qualify for two rescreening opportunities (for a total of three screenings per patient) at the investigator’s discretion.</div>\n<p>\n  </p>\n
      • short_titleCROSSWALK Chronic (C)
      • protocol_noECCT/23/10/01
      • version_no2 (Africa)
      • date_of_protocol06-02-2023
      • study_drugCrovalimab (RO7112689)
      • disease_conditionSICKLE CELL DISEASE (SCD)
      • 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_namePlacebo
      • comparator_registeredN/A
      • comparator_countriesN/A
      • 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_applicantDr. Faith Wanjau
      • declaration_date122-08-2023
      • declaration_principal_investigatorProf. Fredrick Chite Asirwa
      • declaration_date222-08-2023
      • placebo_presentYes
      • study_objectives<ul>\n <li>\n The primary efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo on the basis of the following endpoint:  Annualized rate of medical facility VOEs (AVR) as defined in Section 4.5.1.1 of the protocol</li>\n</ul>\n<div>\n <ul>\n <li>\n The secondary efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo on the basis of the following endpoints:</li>\n </ul>\n <div>\n - Annualized rate of home VOE (defined in Section 4.5.1.5) captured by patient report on a handheld device at home</div>\n <div>\n - Annualized rate of uncomplicated medical facility VOE as defined in Section 4.5.1.2</div>\n <div>\n - Annualized rate of ACS as defined in Section 4.5.1.3</div>\n <div>\n - Annualized rate of days hospitalized for medical facility VOE (defined in Section 4.5.1.1)</div>\n <div>\n - Annualized rate of days hospitalized for treatment of non-VOE complications of SCD (defined in Section 4.5.1.7)</div>\n <div>\n - Change in hematologic measures from baseline to Week 49</div>\n <div>\n - Time to first medical facility VOE from randomization as defined in primary efficacy endpoint (Section 4.5.1.1)</div>\n <div>\n - Change in urinary albumin-creatinine ratio from baseline to Week 49</div>\n <div>\n - Change from baseline to Week 49 in tricuspid regurgitant jet velocity (TRV)</div>\n <div>\n - Proportion of patients with TRV more than 2.5 m/s at Week 49</div>\n <div>\n - Change from baseline to Week 49 in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue score in adults</div>\n <div>\n <ul>\n <li>\n The exploratory efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo on the basis of the following endpoints:</li>\n </ul>\n <div>\n -  Combined rate of VOEs leading to medical facility visit (defined in Section 4.5.1.1) or treated only at home (defined in Section 4.5.1.5)</div>\n <div>\n - Annualized rate of home VOE (defined in Section 4.5.1.5) captured by patient recall at study clinic visits</div>\n <div>\n - Annualized number of RBC transfusions</div>\n <div>\n - Endpoints collected during any medical facility VOE (defined in Section 4.5.1.1) and requiring hospitalization between baseline visit and Week 49:</div>\n <div>\n – Re-admission rate for a subsequent medical facility VOE within 28 days of</div>\n <div>\n discharge</div>\n <div>\n – Duration in days of hospitalization for each medical facility VOE</div>\n <div>\n – Need for RBC transfusion during admission for each medical facility VOE</div>\n <div>\n  </div>\n <div>\n - Change from baseline to Week 49 in the scores of the following PROs:</div>\n <div>\n - Emotional impact and stiffness impact as assessed by the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) in adults</div>\n <div>\n - Physical functioning as assessed by the PROMIS Physical Function in adults</div>\n <div>\n <div>\n - Physical functioning as assessed by the Pediatric Quality of Life Inventory (PedsQL) Core in adolescents</div>\n <div>\n - Fatigue as assessed by the PROMIS Pediatric Fatigue in adolescents</div>\n </div>\n </div>\n</div>\n<ul>\n <li>\n The safety objective for this study is to evaluate the safety and tolerability of crovalimab compared with placebo on the basis of the following endpoints:</li>\n</ul>\n<div>\n - Incidence and severity of adverse events with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events,</div>\n<div>\n Version 5.0 (NCI CTCAE v5.0)</div>\n<div>\n - Change from baseline in targeted vital signs and clinical laboratory test results of clinical significance</div>\n<div>\n - Incidence and severity of injection-site reactions, infusion-related reactions (IRRs), hypersensitivity, and infections (including meningococcal meningitis)</div>\n<div>\n <ul>\n <li>\n The PK objective for this study is to evaluate the pharmacokinetics of crovalimab on the basis of the following endpoint:</li>\n </ul>\n <div>\n - Serum concentrations of crovalimab over time</div>\n <ul>\n <li>\n The exploratory PK objective for this study is:</li>\n </ul>\n <div>\n - To evaluate potential relationships between drug exposure, pharmacodynamics, efficacy, and safety of crovalimab (in patients randomized to crovalimab)</div>\n <div>\n <ul>\n <li>\n The immunogenicity objective for this study is to evaluate the immune response to crovalimab on the basis of the following endpoints:</li>\n </ul>\n <div>\n - Prevalence of ADAs at baseline and incidence of ADAs during the study (patients randomized to crovalimab)</div>\n <div>\n  </div>\n <ul>\n <li>\n The exploratory immunogenicity objective for this study is:</li>\n </ul>\n <div>\n - To evaluate the potential effects of ADA on PD, efficacy, safety, and PK endpoints</div>\n <div>\n <ul>\n <li>\n The exploratory biomarker objective for this study is to identify and/or evaluate biomarkers that are predictive of a response to crovalimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), are associated with resistance to crovalimab, are associated with susceptibility to developing adverse events or can lead to improved adverse event monitoring or investigation (i.e., safety biomarkers), can provide evidenceof crovalimab activity (i.e., PD biomarkers), or can increase the knowledge and understanding of disease biology on the basis of the following endpoints:</li>\n </ul>\n <div>\n - Change over time in PD biomarkers, including CH50 measured by a LIA, total and free C5 concentrations, and sC5b-9 concentration</div>\n <div>\n - Change over time in additional exploratory biomarkers, including, but not limited to, markers of hemolysis, immune cell activation, inflammation, endothelial/vascular damage, and end-organ injury</div>\n <div>\n - Relationship between biomarkers in blood and urine and efficacy, safety, PK, immunogenicity, or other biomarker endpoints</div>\n <div>\n - Change in biomarkers collected during hospitalization for medical facility VOE, from baseline to discharge</div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p 1ex=\"\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Inclusion Criteria:</span></span></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 <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Body weight >=40 kg.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia).</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Two or more (>=2) to <=10 documented VOEs in the 12 months prior to randomisation.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">If receiving concurrent SCD-directed therapy, the participant must have been on a stable dose for a minimum of 3 months prior to study enrollment. There should be no plans to modify the participants' dosing throughout the study duration, other than for safety reasons.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">If receiving erythropoietin, the participant must have been prescribed this medication for the preceding 3 months and be dose-stabilised for at least 3 months prior to study enrollment.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Vaccination against N. meningitides serotypes A, C, W, and Y and Vaccinations against H. influenza type B and S. pneumonia.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Participants who have been vaccinated (partially or in full) against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Adequate hepatic and renal function.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">For women of childbearing potential: agreement to remain abstinent or use contraception during the treatment period and for 10.5 months after the final dose of study treatment.</span></span></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 <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Exclusion Criteria:</span></span></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 <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">History of hematopoietic stem cell transplant.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Received active treatment on another investigational trial within 28 days (or within five half-lives of that agent, whichever is greater) prior to screening visit, or plans to participate in another investigational drug trial.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Hemoglobin <6 g/dL.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Known or suspected hereditary complement deficiency.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Presence of fever (>=38 degrees Celsius) within 7 days before the first drug administration.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Immunised with a live attenuated vaccine within 1 month before first drug administration.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Pregnant or breastfeeding, or intending to become pregnant during the study or within 10.5 months after the final dose of study treatment.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Known HIV infection with documented CD4 count <200 cells/microliter within 24 weeks prior to screening.</span></span></li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">History of N. meningitidis infection within the prior 6 months.</span></span></li>\n</ul>\n
      • primary_end_points<ul>\n <li>\n <span style=\"font-size:12px;\">The primary efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo on the basis of the following endpoint:  Annualized rate of medical facility VOEs (AVR) as defined in Section 4.5.1.1 of the protocol</span></li>\n</ul>\n<div>\n <ul>\n <li>\n <span style=\"font-size:12px;\">The secondary efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo on the basis of the following endpoints:</span></li>\n </ul>\n <div>\n <span style=\"font-size:12px;\">- Annualized rate of home VOE (defined in Section 4.5.1.5) captured by patient report on a handheld device at home</span></div>\n <div>\n <span style=\"font-size:12px;\">- Annualized rate of uncomplicated medical facility VOE as defined in Section 4.5.1.2</span></div>\n <div>\n <span style=\"font-size:12px;\">- Annualized rate of ACS as defined in Section 4.5.1.3</span></div>\n <div>\n <span style=\"font-size:12px;\">- Annualized rate of days hospitalized for medical facility VOE (defined in Section 4.5.1.1)</span></div>\n <div>\n <span style=\"font-size:12px;\">- Annualized rate of days hospitalized for treatment of non-VOE complications of SCD (defined in Section 4.5.1.7)</span></div>\n <div>\n <span style=\"font-size:12px;\">- Change in hematologic measures from baseline to Week 49</span></div>\n <div>\n <span style=\"font-size:12px;\">- Time to first medical facility VOE from randomization as defined in primary efficacy endpoint (Section 4.5.1.1)</span></div>\n <div>\n <span style=\"font-size:12px;\">- Change in urinary albumin-creatinine ratio from baseline to Week 49</span></div>\n <div>\n <span style=\"font-size:12px;\">- Change from baseline to Week 49 in tricuspid regurgitant jet velocity (TRV)</span></div>\n <div>\n <span style=\"font-size:12px;\">- Proportion of patients with TRV more than 2.5 m/s at Week 49</span></div>\n <div>\n <span style=\"font-size:12px;\">- Change from baseline to Week 49 in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue score in adults</span></div>\n <div>\n <ul>\n <li>\n <span style=\"font-size:12px;\">The exploratory efficacy objective for this study is to evaluate the efficacy of crovalimab compared with placebo on the basis of the following endpoints:</span></li>\n </ul>\n <div>\n <span style=\"font-size:12px;\">-  Combined rate of VOEs leading to medical facility visit (defined in Section 4.5.1.1) or treated only at home (defined in Section 4.5.1.5)</span></div>\n <div>\n <span style=\"font-size:12px;\">- Annualized rate of home VOE (defined in Section 4.5.1.5) captured by patient recall at study clinic visits</span></div>\n <div>\n <span style=\"font-size:12px;\">- Annualized number of RBC transfusions</span></div>\n <div>\n <span style=\"font-size:12px;\">- Endpoints collected during any medical facility VOE (defined in Section 4.5.1.1) and requiring hospitalization between baseline visit and Week 49:</span></div>\n <div>\n <span style=\"font-size:12px;\">– Re-admission rate for a subsequent medical facility VOE within 28 days of</span></div>\n <div>\n <span style=\"font-size:12px;\">discharge</span></div>\n <div>\n <span style=\"font-size:12px;\">– Duration in days of hospitalization for each medical facility VOE</span></div>\n <div>\n <span style=\"font-size:12px;\">– Need for RBC transfusion during admission for each medical facility VOE</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:12px;\">Change from baseline to Week 49 in the scores of the following PROs:</span></div>\n <div>\n <span style=\"font-size:12px;\">- Emotional impact and stiffness impact as assessed by the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) in adults</span></div>\n <div>\n <span style=\"font-size:12px;\">- Physical functioning as assessed by the PROMIS Physical Function in adults</span></div>\n <div>\n <div>\n <span style=\"font-size:12px;\">- Physical functioning as assessed by the Pediatric Quality of Life Inventory (PedsQL) Core in adolescents</span></div>\n <div>\n <span style=\"font-size:12px;\">- Fatigue as assessed by the PROMIS Pediatric Fatigue in adolescents</span></div>\n </div>\n </div>\n <div>\n  </div>\n</div>\n<ul>\n <li>\n <span style=\"font-size:12px;\">The safety objective for this study is to evaluate the safety and tolerability of crovalimab compared with placebo on the basis of the following endpoints:</span></li>\n</ul>\n<div>\n <span style=\"font-size:12px;\">- Incidence and severity of adverse events with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events,</span></div>\n<div>\n <span style=\"font-size:12px;\">Version 5.0 (NCI CTCAE v5.0)</span></div>\n<div>\n <span style=\"font-size:12px;\">- Change from baseline in targeted vital signs and clinical laboratory test results of clinical significance</span></div>\n<div>\n <span style=\"font-size:12px;\">- Incidence and severity of injection-site reactions, infusion-related reactions (IRRs), hypersensitivity, and infections (including meningococcal meningitis)</span></div>\n<div>\n <ul>\n <li>\n <span style=\"font-size:12px;\">The PK objective for this study is to evaluate the pharmacokinetics of crovalimab on the basis of the following endpoint:</span></li>\n </ul>\n <div>\n <span style=\"font-size:12px;\">- Serum concentrations of crovalimab over time</span></div>\n <ul>\n <li>\n <span style=\"font-size:12px;\">The exploratory PK objective for this study is:</span></li>\n </ul>\n <div>\n <span style=\"font-size:12px;\">- To evaluate potential relationships between drug exposure, pharmacodynamics, efficacy, and safety of crovalimab (in patients randomized to crovalimab)</span></div>\n <div>\n <ul>\n <li>\n <span style=\"font-size:12px;\">The immunogenicity objective for this study is to evaluate the immune response to crovalimab on the basis of the following endpoints:</span></li>\n </ul>\n <div>\n <span style=\"font-size:12px;\">- Prevalence of ADAs at baseline and incidence of ADAs during the study (patients randomized to crovalimab)</span></div>\n <ul>\n <li>\n <span style=\"font-size:12px;\">The exploratory immunogenicity objective for this study is:</span></li>\n </ul>\n <div>\n <span style=\"font-size:12px;\">- To evaluate the potential effects of ADA on PD, efficacy, safety, and PK endpoints</span></div>\n <div>\n <ul>\n <li>\n <span style=\"font-size:12px;\">The exploratory biomarker objective for this study is to identify and/or evaluate biomarkers that are predictive of a response to crovalimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), are associated with resistance to crovalimab, are associated with susceptibility to developing adverse events or can lead to improved adverse event monitoring or investigation (i.e., safety biomarkers), can provide evidenceof crovalimab activity (i.e., PD biomarkers), or can increase the knowledge and understanding of disease biology on the basis of the following endpoints:</span></li>\n </ul>\n <div>\n <span style=\"font-size:12px;\">- Change over time in PD biomarkers, including CH50 measured by a LIA, total and free C5 concentrations, and sC5b-9 concentration</span></div>\n <div>\n <span style=\"font-size:12px;\">- Change over time in additional exploratory biomarkers, including, but not limited to, markers of hemolysis, immune cell activation, inflammation, endothelial/vascular damage, and end-organ injury</span></div>\n <div>\n <span style=\"font-size:12px;\">- Relationship between biomarkers in blood and urine and efficacy, safety, PK, immunogenicity, or other biomarker endpoints</span></div>\n <div>\n <span style=\"font-size:12px;\">- Change in biomarkers collected during hospitalization for medical facility VOE, from baseline to discharge</span></div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • 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_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n This has been elaborated in the the respective site specific addendums attached in the checklist sections.</p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable</span></p>\n
      • other_details_regulatory_notapproved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable</span></p>\n
      • other_details_regulatory_approved<p>\n <span id=\"docs-internal-guid-2960da1a-7fff-1f77-6bb2-0c6db95a0e16\"><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; vertical-align: baseline; white-space-collapse: preserve;\"><span style=\"border:none;display:inline-block;overflow:hidden;width:415px;height:246px;\"><img height=\"246\" src=\"https://lh4.googleusercontent.com/bcTJE_1-Joi-ANNDdm_3DCSU9iPAAZO-zj_GISuBiJfHmAclaXv0uOtZG1_rjeM7g_hiSiKuLeZmtTLKe7dp6drlPqX5upUccV9MU_L5ceJFKbPSOu5ycFpF8qgh2pVzwYv4oRbumCcioNl8IJoEKg\" style=\"margin-left:0px;margin-top:0px;\" width=\"415\" /></span></span></span></p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_durationThe total length of the study, from screening of the first patient to the end of the study, is expected to be approximately 3.5 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_comparatorN/A
      • 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_states10
      • number_of_sites2
      • multi_country_listBrazil France Italy Spain Turkey USA UK Netherlands South Africa Lebanon
      • data_monitoring_committeeYes
      • total_enrolment_per_siteGertrude\'s Children\'s Hospital- At least 5 patients \nInternational Cancer Institute- At least 5 patients
      • total_participants_worldwide90
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • 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_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFredrick
      • investigator1_middle_nameChite
      • investigator1_family_nameAsirwa
      • investigator1_qualificationProfessor of Hematology and Oncology
      • investigator1_professional_addressInternational Cancer Institute, Nandi Road 8/10, Eldoret, Kenya, 8088-30100
      • investigator1_telephone+254 700 522 149
      • investigator1_emaildirector@intercancer.com
      • organisations_transferred_Yes
      • number_participants15 patients
      • notification
      • approval_date10-01-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted02-10-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been resolved
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-12-31 17:46:40
      • created2023-08-18 14:02:18
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id956
        • application_id1300
        • given_nameFredrick
        • middle_nameChite
        • family_nameAsirwa
        • qualificationProfessor of Hematology and Oncology
        • professional_addressInternational Cancer Institute, Nandi Road 8/10, Eldoret, Kenya, 8088-30100
        • telephone+254 700 522 149
        • emaildirector@intercancer.com
        • created2023-08-18 15:32:28
        • modified2023-10-02 12:06:01
      • 1(array)
        • id957
        • application_id1300
        • given_nameDoreen
        • middle_nameTerry
        • family_nameKarimi
        • qualificationHospital Resident Pediatrician
        • professional_addressGertrudes Childrens Hospital
        • telephone0722384218
        • emailtessmutua@gmail.com
        • created2023-08-18 15:48:10
        • modified2023-10-02 12:06:01
    • SiteDetail(array)
      • 0(array)
        • id1573
        • application_id1300
        • county_id47
        • site_nameGertrudes Childrens Hospital
        • physical_addressMuthaiga, Nairobi
        • contact_detailsP. O. Box 42325 -00100 GPO NAIROBI
        • contact_personDr. Doreen Karimi Mutua -0722384218
        • site_capacity(null)
        • misc(null)
        • created2023-08-18 15:32:28
        • modified2023-10-02 12:06:01
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1574
        • application_id1300
        • county_id27
        • site_nameInternational Cancer Institute
        • physical_addressEldoret, Kenya
        • contact_detailsNandi Road 8/10, Eldoret, Kenya, 8088-30100
        • contact_personProfessor Chite Asirwa
        • site_capacity(null)
        • misc(null)
        • created2023-08-18 16:00:10
        • modified2023-10-02 12:06:01
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
    • Sponsor(array)
      • 0(array)
        • id685
        • application_id1300
        • sponsorHoffmann La Roche
        • sponsor_typeIndustry
        • contact_personDr. Eileen Koske
        • addressP.O. Box 44212-00100 Nairobi, Kenya
        • telephone_number +254 721375237
        • fax_number
        • cell_number +254 721375237
        • email_addresseileen.koske@roche.com
        • created2023-08-18 15:32:28
        • modified2023-10-02 12:06:01
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(empty)
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
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  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

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  • Config(array)
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