Request History

• Restore to current request
• applications/index/page:63/sort:protocol_no/direction:desc/approved:1
• applications/index/page:72/sort:study_title/direction:desc/approved:2
• applications/index/page:71/sort:protocol_no/direction:asc/approved:2
• applications/index/page:64/sort:study_title/direction:desc/approved:1

Session

• Config(array)
  • userAgent9c3d2c89526db53b7b69e8c9faa06145
  • time1746063848
  • countdown10

Request

Cake Params

• plugin(null)
• controllerapplications
• actionindex
• named(array)
  • page71
  • sortprotocol_no
  • directiondesc
  • approved2
• pass(empty)
• isAjax(false)
• paging(array)
  • Application(array)
    • page71
    • current5
    • count502
    • prevPage(true)
    • nextPage(true)
    • pageCount101
    • order(array)
      • Application.protocol_nodesc
    • limit5
    • options(array)
      • page71
      • order(array)
        • Application.protocol_nodesc
      • sortprotocol_no
      • directiondesc
    • paramTypenamed

Post data

• Application(array)
  • approved2

Query string

No querystring data.

Cookie

To view Cookies, add CookieComponent to Controller

Current Route

• keys(array)
  • 0controller
  • 1action
• options(empty)
• defaults(array)
  • plugin(null)
• template/:controller/:action/*

Sql Logs

Logs

View Variables

• trial_statuses(array)
  • 1Recruiting
  • 2Not yet recruiting
  • 3Suspended
  • 4Stopped
  • 5Completed
  • 6In follow-up
  • 7Analysing
  • 8Writing-up
  • 9Application withdrawn
• applications(array)
  • 0(array)
    • Application(array)
      • id578
      • user_id73
      • trial_status_id4
      • abstract_of_study<p>\n Women account for a large proportion of new HIV infections globally. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated that Tenofovir (TFV) vaginal gel reduced HIV acquisition by an estimated 39% overall. There are difficulties with adherence to daily or pericoitally dosed intravaginal gels. The development of delivery systems that overcome difficulties associated with adherence, such as intravaginal rings, may result in greater reductions in the rates of HIV-1 infection.</p>\n<p>\n This phase 1 study is a two-site, two-arm, randomized single-blind placebo-controlled trial which aims to assess safety of Tenofovir Disoproxil Fumarate (TDF) Intravaginal Ring (IVR) when used by healthy, HIV uninfected, sexually active women, as compared with the placebo IVR. Secondary objectives are to examine systemic and genital tract pharmacokinetics (PK) of TDF and its metabolites and evaluate the acceptability of the study IVR.</p>\n<p>\n The study will be conducted in Albert Einstein College of Medicine (Einstein), Bronx, USA and Partners in Health & Research Development Site, Thika, Kenya. The study will recruit 80 women (40 US and 40 African) who are Healthy, sexually active, HIV uninfected between the ages of 18 and 45 on contraception.</p>\n<p>\n Accrual of participants will require approximately 12 months. Each participant will engage in the screening process for up to 28 days prior to enrolment. Enrolled participants will use the TDF IVR continuously for 84 days, and will have clinic visits every 14 days. Twenty US women will participate in a 30-day run-in phase to assess safety prior to initiation of enrollment in Kenya.</p>\n
      • study_title<p align=\"center\">\n <strong>Phase 1 Safety and Pharmacokinetic Study of a Polyurethane Tenofovir Disoproxil Fumarate Vaginal Ring in Sexually Active Women (TDF IVR-002)</strong></p>\n
      • laymans_summary(null)
      • short_titleTDF IVR-002 Study
      • protocol_noECCT/17/05/03
      • version_no2.0
      • date_of_protocol30-08-2016
      • study_drugTenofovir Disoproxil Fumarate in IVR (TDF IVR)
      • disease_conditionSafety of TDF IVR in prevention of HIV acquisition
      • 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_nameTenofovir Disoproxil Fumarate in IVR (TDF IVR)
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressRwamba@csrtkenya.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_countries1
      • 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. Kenneth Ngure
      • declaration_date108-05-2017
      • declaration_principal_investigatorDr. Nelly R. Mugo
      • declaration_date208-05-2017
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n Women must meet all the following criteria to be eligible for inclusion in the study:</p>\n<ul>\n <li>\n Age 18-45 years (inclusive) at screening.</li>\n <li>\n General good health (by volunteer history and per investigator discretion) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, osteoporosis or bone disease, and diabetes).</li>\n <li>\n Able and willing to provide written informed consent to be screened for and take part in the study.</li>\n <li>\n Able and willing to provide adequate locator information.</li>\n <li>\n Able and willing to avoid receptive vaginal and anal intercourse for 1 week after each biopsy.</li>\n <li>\n HIV-uninfected based on testing performed by study staff during screening procedures (per applicable algorithm in Appendix II).</li>\n</ul>\n<ul>\n <li>\n Using a copper IUD or any hormonal contraceptive method, other than an IVR, for a minimum of 2 months and intending to use the same method for the duration of study participation.</li>\n <li>\n Per participant report, sexually active, defined as having vaginal intercourse at least once in the month prior to screening.</li>\n</ul>\n<ul>\n <li>\n Have a regular sex partner and willing to have at least 4 sex acts per month for the duration of the study. <em>Sex act is defined as penile-vaginal penetrative intercourse. Study staff will provide condoms to all study participants. Participants will not be restricted from engaging in oral sex. </em></li>\n <li>\n Has not used pre- or post-exposure prophylaxis for HIV exposure in the 3 months prior to Screening.</li>\n <li>\n Per participant report at Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, or vaginal products for the duration of study participation.</li>\n <li>\n At Screening, participant states she is able and willing to refrain from taking traditional herbs or medicines and is willing to refrain from inserting any non-study vaginal products or objects into the vagina, including but not limited to, spermicides, diaphragms, contraceptive vaginal rings, vaginal medications, vaginal probiotics/pre-biotics, menstrual cups, cervical caps (or any other vaginal barrier method), douches, lubricants, vaginal drying agents and sex toys (vibrators, dildos, etc.). <em>Tampons may be used, but for menses only.</em></li>\n <li>\n Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy genital tract sample collection.      </li>\n</ul>\n
      • principal_exclusion_criteria<p>\n Women must meet none of the following criteria prior to genital sampling at Enrollment:</p>\n<ul>\n <li>\n Participant report of any of the following at Screening:</li>\n <li style=\"margin-left: 0.75in;\">\n Sex in the past 3 months or any possibility of sex during study participation with a partner who is HIV+ or with a partner of unknown HIV status.</li>\n <li style=\"margin-left: 0.75in;\">\n Known adverse reaction to polyurethane or to any components of the study product or allergy to both silver nitrate and Monsel’s solution.</li>\n <li style=\"margin-left: 0.75in;\">\n Active hepatitis B infection.</li>\n <li style=\"margin-left: 0.75in;\">\n Chronic, recurrent, and/or acute vulvar or vaginal symptoms (pain, irritation, spotting, etc.).</li>\n <li style=\"margin-left: 0.75in;\">\n Known bleeding disorder that could lead to prolonged or continuous bleeding with biopsy.</li>\n <li style=\"margin-left: 0.75in;\">\n Intending to become pregnant during the period of study participation.</li>\n <li style=\"margin-left: 0.75in;\">\n Currently breastfeeding or planning to breastfeed during the course of the study.</li>\n <li style=\"margin-left: 0.75in;\">\n Menopause.</li>\n <li style=\"margin-left: 0.75in;\">\n History of unexplained or unresolved intermenstrual bleeding in the 3 months prior to screening.</li>\n <li style=\"margin-left: 0.75in;\">\n History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix in the last 14 days.</li>\n <li style=\"margin-left: 0.75in;\">\n Hysterectomy.</li>\n <li style=\"margin-left: 0.75in;\">\n Women using contraceptive IVRs because the study product is an IVR.</li>\n <li style=\"margin-left: 0.75in;\">\n Systemic use in the last 2 weeks or anticipated use during the study period of any of the following: corticosteroids, anticoagulants or ARVs.</li>\n <li style=\"margin-left: 0.75in;\">\n Plans to relocate away from the study site area during the period of study participation.</li>\n</ul>\n<p style=\"margin-left:.5in;\">\n ·        Grade 1 or higher laboratory abnormality, as defined by the DAIDS Table for Grading the Severity of Adult and Pediatric AEs, Version 2.0, Nov 2014.</p>\n<p style=\"margin-left:.5in;\">\n ·         At Screening or Enrollment, is pregnant (based on urine pregnancy test).</p>\n<p style=\"margin-left:.5in;\">\n ·         In the last three months, diagnosed with or treated for any STI.</p>\n<p style=\"margin-left:.5in;\">\n <em>Note: Women with a history of condylomata </em>or <em>genital herpes may be considered for eligibility as long as there are no lesions on exam. HSV 1 and 2 serologies will be obtained. Participants will be included regardless of the results of these serologies</em>.   </p>\n<p style=\"margin-left:.5in;\">\n ·         Reproductive tract infection (RTI) or pelvic inflammatory disease (PID) requiring treatment per local guidelines in Kenya and CDC guidelines in the US at Screening or Enrollment.</p>\n<p style=\"margin-left:.5in;\">\n <em>Note: Otherwise eligible women diagnosed with symptomatic vulvovaginal candidiasis (VVC)</em>,<em> symptomatic BV or urinary tract infection (UTI) will be eligible if Visit 2 (Enrollment) is scheduled after all symptoms have resolved and at least two weeks after completing treatment. Women with recurrent VVC and symptomatic BV despite treatment will be offered another course of treatment and will not be eligible.</em></p>\n<p style=\"margin-left:.5in;\">\n ·         Positive test for <em>Trichomonas vaginalis</em>, <em>Neisseria go</em><em>norrhea</em> or <em>Chlamydia trachomatis</em> at screening.</p>\n<p style=\"margin-left:.5in;\">\n ·         Positive test for hepatitis B (defined as positive for hepatitis B surface antigen).</p>\n<p style=\"margin-left:.5in;\">\n ·         Reactive serologic test for syphilis at screening (per local guidelines).</p>\n<p style=\"margin-left:.5in;\">\n <em>Note: Women with a history of syphilis that was not acquired and/or treated within the past 3 months and that has been appropriately treated may be considered for eligibility. </em></p>\n<p style=\"margin-left:.5in;\">\n ·         At Screening or Enrollment, has a clinically apparent Grade 1 or higher pelvic exam finding (observed by study clinician or designee) per the DAIDS Table for Grading the Severity of Adult and Pediatric AEs, Addendum 1, Female Genital Grading Table for Use in Microbicide Studies.</p>\n<p style=\"margin-left:.5in;\">\n <em>Note: Cervical friability bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the PL/designee is considered expected non-menstrual bleeding and is not exclusionary.</em></p>\n<p style=\"margin-left:.5in;\">\n ·         Pap result Grade 2 or higher according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric AEs, Version 1.0, December 2004 (Clarification dated August 2009).</p>\n<p style=\"margin-left:.5in;\">\n <em>Note: Women 21 years of age or older with a documented normal result within the 12 months prior to enrollment need not have Pap smear during the screening period. Women with a Grade 1 abnormal Pap smear can be enrolled upon completion of the initial phase of evaluation if no current treatment is indicated (based on local standard of care for management of abnormal cervical cytology). Need for a repeat Pap within 6 months does not preclude enrollment prior to that result becoming available. </em></p>\n<p style=\"margin-left:.5in;\">\n ·         At Screening, has severe pelvic relaxation such that either the vaginal walls or the uterine cervix descend beyond the vaginal introitus with Valsalva maneuver.</p>\n<p style=\"margin-left:.5in;\">\n ·         Has any condition that, in the investigator’s opinion, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.</p>\n
      • primary_end_points<p style=\"margin-left:2.0in;\">\n The proportion of women in each arm experiencing adverse events (AEs):</p>\n<p style=\"margin-left:2.0in;\">\n Genitourinary events Grade 2 or higher as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events judged to be related to study product.</p>\n<p style=\"margin-left:2.0in;\">\n Adverse events Grade 2 or higher as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifySecond administration to humans
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Partners in Health & Research Development (Formerly Partners in Prevention), has 38 full time clinical trial staff (including physicians, nurses, counsellors, pharmacists, social scientists ).</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Principal Investigator: Dr. Nelly R. Mugo  MBCHB,MMED,MPH</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Co-Investigator: Dr. Kenneth Ngure  BSc,MPH,MSc,PhD</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n
      • other_details_explanation<p>\n This clinical trial will be conducted in Kenya and the United States. In Kenya, it will be conducted at Partners in Health Research and Development, Thika site. The The Thika site is located 25 miles northeast of Nairobi in Kiambu County Kenya. The rates of sexually transmitted infection (STI) in previous studies have been fairly low. The most common infections are Trichomonas and candidiasis. The prevalence of HIV is higher among women (5.6%) in Kiambu County than in men (2%). The flow of participants through the Thika clinic includes a counseling visit that is focused on the prevention of STI, including HIV. The counselors are skilled and experienced in HIV and STI risk reduction. This experience is demonstrated through the lowered HIV-1 incidence among participants at high risk for HIV randomized to the placebo arm to less than 2% (HSV/HIV Transmission Study and Partners PrEP Study) compared to incidence rates of 10-14% reported elsewhere.</p>\n<p>\n The fact that there is a high rate of HIV and STI is known in the Thika community, and many women want to take an active part in designing potential solutions, and their families support such involvement. The Thika team has worked with the local community conducting research for the past 10 years. The site also has extensive experience collecting biopsies in research studies. </p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Kenya Medical Research Institute's ERC - 8 December 2016</p>\n<p>\n University of Washington IRB                     - 24 May 2016</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration2 Years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindYes
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo IVR
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaPartners in Health Research & Development (Thika Partners Clinical Trial Site)
      • single_site_physical_addressOAU Road, Near Thika Nursing Home, Thika Section 9 P.O Box 19865-00202 Contact person County Kiambu
      • single_site_contact_personDr. Kenneth Ngure
      • single_site_telephone067 2222561
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_listUnited States of America \nKenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site40
      • total_participants_worldwide80
      • 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_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMarla
      • investigator1_middle_name
      • investigator1_family_nameKeller
      • investigator1_qualificationMD, Professor
      • investigator1_professional_addressAlbert Einstein College of Medicine, 1300 Morris Park Avenue, Block Building, Room 512, Bronx, NY 10461
      • investigator1_telephone718-430-3240
      • investigator1_emailmarla.keller@einstein.yu.edu
      • organisations_transferred_Yes
      • number_participants40
      • notification
      • approval_date18-07-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted23-05-2017
      • 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)
      • modified2017-10-16 09:17:33
      • created2016-12-22 16:57:51
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id374
        • application_id578
        • given_nameNelly
        • middle_nameRwamba
        • family_nameMugo
        • qualificationMBChB, MMeD, MPH
        • professional_address19865-00202
        • telephone067-2222561, 0723914057
        • emailrwamba@csrtkenya.org
        • created2016-12-22 16:58:58
        • modified2017-05-23 13:21:33
    • SiteDetail(array)
      • 0(array)
        • id471
        • application_id578
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-12-22 16:58:58
        • modified2017-05-23 13:21:33
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id300
        • application_id578
        • sponsorAlbert Einstein College of Medicine
        • sponsor_type(null)
        • contact_personDr. Nelly Rwamba Mugo
        • address19865 - 00202
        • telephone_number067-2222561,
        • fax_number
        • cell_number0723914057
        • email_addressrwamba@csrtkenya.org
        • created2016-12-22 16:58:58
        • modified2017-05-23 13:21:33
  • 1(array)
    • Application(array)
      • id603
      • user_id365
      • trial_status_id8
      • abstract_of_study<p>\n <strong>Purpose: </strong>The goals of this project are; to identify and test 700 men who have sex with men (MSM); to assess the success of a comprehensive package of find, test, link and retain in care (FTLR) interventions delivered to HIV-infected MSM; to retain those who test negative in a peer-led behavioral risk reduction program that includes retesting every 3 months; and to offer pre exposure prophylaxis (PrEP) to a subset of the negative men who are at high risk for HIV acquistion.</p>\n<p>\n <strong>Significance: </strong>This study will generate evidence to inform <strong>feasibility, acceptability, and expected outputs</strong> necessary to guide PEPFAR programming for expansion of counseling, testing, and comprehensive care and treatment as effective HIV prevention interventions adapted for MSM in sub-Saharan Africa.</p>\n<p>\n <strong>Design: </strong>This is an observational cohort study. Over 6 months, 700 MSM will be tested and counseled for HIV. Outreach will occur using existing peer networks, snowballing, and Time Location Recruitment (TLR) strategies. Those who meet the eligibility criteria will be asked to enroll in the study. HIV-positive participants will be recruited into care and offered ART, regardless of CD4 count, then followed up for retention in care and treatment adherence. HIV-negative participants will be recruited to a risk reduction program with quarterly counseling, linkage to support groups, and repeat HIV counseling and testing every 3 months. A subset of HIV-negative participants will be offered PrEP. Each participant will be followed for 12 months from enrolment or from PrEP initiation, during which structured HIV behavioral assessments, medical examinations, and collection of biological samples for STI/HIV tests will be conducted. Mid-way and exit qualitative interviews with participants will explore barriers to retention in periodic testing and HIV prevention. Participants who do not complete 12 months of follow-up will be contacted to explore reasons for no longer participating. Approximately 30 clinicians and peer outreach staff will be interviewed to get their views on unmet needs and program improvement.</p>\n<p>\n <strong>Study Population: </strong>Men who report oral or anal sex with a man in the past 6 months, are ≥18 years of age, and are residents of Kisumu, irrespective of HIV infection status.      </p>\n<p>\n <strong>Study Size: </strong>A total of approximately 700 men will be enrolled, plus approximately 30 staff.</p>\n<p>\n <strong>Study: </strong>Total study duration is 24 months</p>\n<p>\n <strong>Study Aims: </strong>            Aim 1: To find and test 700 MSM for HIV</p>\n<p style=\"margin-left: 80px;\">\n          Aim 2: To link and retain HIV-positive MSM in HIV care including ART</p>\n<p style=\"margin-left: 80px;\">\n          Aim 3: To link and retain HIV-negative MSM in a non-ART care and risk reduction program including retesting every 3 months post-enrollment</p>\n<p style=\"margin-left: 80px;\">\n          Aim 4: To assess uptake and adherence to PrEP among a subset of high risk HIV-negative MSM</p>\n<p>\n <strong>Study Sites</strong>:             Anza Mapema, Tom Mboya, Kisumu and Kisumu Town Office</p>\n
      • study_title<p>\n <strong>Expanding test and treat for HIV prevention in MSM in Kisumu, Kenya: T</strong><strong>he Anza Mapema Study</strong></p>\n
      • laymans_summary(null)
      • short_titleThe Anza Mapema Study
      • protocol_noECCT/17/05/02
      • version_no7
      • date_of_protocol20-09-2016
      • study_drugTruvada
      • disease_conditionHIV
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameTDF/FTC
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressfotieno@nrhskenya.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 Fredrick Odhiambo Otieno
      • declaration_date110-04-2017
      • declaration_principal_investigatorDr Fredrick Odhiambo Otieno
      • declaration_date210-04-2017
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n Men must meet all of the following criteria to be eligible for inclusion in this study:</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Biologically male at birth, according to self-report</p>\n<p style=\"margin-left:14.2pt;\">\n ·      ≥18 years of age</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Resident of Kisumu</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Willing and able to provide informed consent</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Agree to be tested for HIV</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Reports at least one act of anal or oral intercourse in the previous 6 months with another man</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Able to provide complete locator identification</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Willing to participate in all scheduled study visits</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Not currently participating in any HIV intervention or vaccine study</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Planning to remain in the study area for at least one year</p>\n
      • principal_exclusion_criteria<p>\n Men who meet any of the following criteria will be excluded from this study:</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Already enrolled in an HIV care program and taking ART within the past 3 months</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Unwilling to adhere to study procedures</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Currently under the influence of alcohol or drugs</p>\n<p style=\"margin-left:14.2pt;\">\n ·      Unable to understand the study purpose and procedures</p>\n
      • primary_end_points<p>\n <strong>Aim 1: </strong>The number of MSM tested and the number and percentage who are newly tested (i.e., first HIV test); the number and percentage of MSM with newly diagnosed HIV; and the number with known HIV who are not in care and have not received ART in the last six months. These process measures will be compared by age-group and testing service (e.g., outreach, clinic, office), providing useful guidance for targeting HIV testing services to MSM.</p>\n<p>\n <strong>Aim 2: </strong>Linkage outcomes will be time to engagement in care (i.e., visit with an ART provider), proportion linked to care within 4 weeks of testing, proportion initiating ART, and time from enrolment to ART initiation. The primary retention outcome will be missed follow-up visits and completion of 12 months of study follow-up. For those men who initiate ART, the primary outcome measures are adherence, defined as high adherence (≥90% vs. <90% of pills taken by monthly pill count, as well as self-reported adherence), and virologic suppression (defined as plasma HIV-1 RNA <1,000 copies/mL) at 6 and 12 month visits (59). Virologic suppression will also be measured among those who have not initiated ART at a study clinic, since they may be obtaining ART elsewhere. Lastly, we will examine two primary sexual risk behaviors: any UAI in the past 3 months (yes vs. no); number of sex partners in past 3 months. Men with no outcome data at a given time point will be considered non-adherent, unless a formal study withdrawal with transfer to another clinical care provider is documented. Additional outcomes are sexually transmitted infections (STI) including HSV-2, syphilis, gonorrhea and chlamydia, as well as HBV and HCV infection. For qualitative interviews with staff, the main outcomes include factors perceived to be associated with retention of study participants in care.</p>\n<p>\n <strong>Aim 3: </strong>The primary outcome measure is HIV testing at month 6 and month 12. We will also report the diagnostic yield of HIV testing in this group, estimating number of new infections and HIV incidence in this population. Additional outcomes are reduction in sexual partners and UAI (as above), proportion linked to the program within 4 weeks of testing, proportion completed 12 months of follow-up. Additional outcomes are STIs including HSV-2, syphilis, gonorrhea and chlamydia, as well as HBV and HCV. For the qualitative interviews with staff and study participants, outcomes include perceptions about the barriers and facilitators to retention in HIV treatment, as well as HIV testing and engagement in HIV prevention activities.</p>\n<p>\n <strong>Aim 4: </strong>While PrEP is highly efficacious in reducing risk of HIV acquisition, protection is highly dependent on adherence. In parallel to detection of FTC-TP and TFV-DP, we will assess adherence through pill count, and multiple self-reported measures: visual analog scale (VAS) of 0-100% of pills taken, number of days missed in past week and past month, and frequency of taking pills. Previous studies have used <u>></u>80% vs. <80% by pill count as the cutoff for high adherence, so we will examine drug levels in those above and below those reported levels. Due to cost, we will limit drug testing to 160 subjects. Our sample size of 160 will provide 80% power to detect a 16.7% discordance in adherence by drug vs. pill count of <u>></u>80% of pills taken (McNemar Test for paired measures, two-sided test, alpha=0.05, PASS v11) assuming drug-detected adherence of 50%-67%, which is in keeping with findings from previous PrEP studies. Other outcomes to be analyzed include the associations of PrEP initiation and PrEP adherence with risk behavior outcomes including 1) unprotected anal intercourse in the past 3 months (yes vs. no); 2) number of sex partners in past 3 months (continuous); and 3) incident STI (yes vs. no). We will also examine the incidence of adverse effects and test the few incident HIV cases for the presence of antiretroviral resistance mutations to TDF or FTC. Lastly, we will examine complete follow-up (attended all scheduled visits) and missed visits as outcomes. Complete description of statistical methods and modeling strategies is below.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyStudy assessing adherence and acceptability
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n The Nyanza Reproductive Health Society (NRHS) is a Kenyan NGO established in 2002 and is registered under the Kenyan Societies Act. It has an Executive Board which meets quarterly to oversee NRHS functions and to which the Director reports. NRHS is composed of numerous programs devoted to reproductive health, HIV prevention practice and research, and support for people living with HIV and AIDS (PLWHA). Each program has its own designated accounting staff, overseen by a Finance Director, to ensure compliance with international accounting standards. Audits are conducted annually by a U.S. Government designated auditing firm. Expenses are invoiced monthly. NRHS enjoys the support of numerous Kenyan collaborators as well as the County Governments, community leaders, NGOs, CBOs, the MOH and youth organizations throughout Kisumu and western Kenya. All NRHS activities are coordinated by the Director, Dr. Edmon Obat . Under his supervision is the Scientific Director, Dr. Fredrick Otieno, who has over ten years of experience in clinical practice and research. Dr. Otieno supervises the coordinators for each project and the different sections, which include: clinic staff, counselors, reception/clerical, data management, administrative, human resources, procurement, stores, transport, quality control, and others.</p>\n<p>\n NRHS has in place policies and practices with standard operating procedures for procurement, human resource management, accounting and finance, and inventory. Staff are trained to follow sound and ethical practices regarding all of these areas. All NRHS investigators and staff, except the security guards, have up-to-date Human Subject Protection training and certification. Laboratory staff are GCLP certified and have IATA certification for handling of dangerous goods. All laboratory and research staff are trained in post-exposure prophylaxis. Fire extinguishers are placed throughout the offices and emergency evacuation plans are in place. In cases of clinical emergency, SOPs are in place and transport available to access the major referral hospital in the region, JOOTRH and private hospitals. NRHS has a pool of vehicles available for rent from its different projects. Vehicles are maintained by NRHS transport department staff, and each vehicle has a tracking device to monitor speed and fuel consumption and to map travel.</p>\n<p>\n <em>Community Engagement:</em> NRHS research and community outreach activities are regularly presented and discussed with a community advisory board (CAB) that has provided ongoing feedback on the implementation of HIV prevention research. In addition, the ongoing Anza Mapema program has a CAB that oversees its HIV prevention research with MSM in Kisumu; that CAB will oversee the proposed work in this project.</p>\n<p>\n <em>Clinical: </em>The Anza Mapema research clinic includes 2 reception areas and 1 waiting room, 2 clinical rooms, 2 counseling rooms, 1 outreach and community office, a communal kitchen a data room with cubicles for conducting self-risk assessments (ACASI), a pharmacy and secure office space for keeping records. There is also space for the Project Coordinator, an accountant and common space for Research Assistants. Specimens are stored at the UNIM Research and Training Centre (URTC) laboratory (GCLP-accredited) across town (daily transport of specimens). The clinic is in a large compound with a garden and space for outdoor events; a surrounding wall lends privacy and enhances security. Participants in the field test of our novel MP3 intervention will be followed prospectively at this clinic. The clinic houses a small antiretroviral treatment program, with drugs are supplied by the Kenya National AIDS and STD Control Programme (NASCOP) with PEPFAR support. In addition, CDC directly supports staff training and logistical support for the HIV prevention and care programs at Anza Mapema through PEPFAR.</p>\n<p>\n <em>Laboratory: </em>The URTC laboratory has capacity for receipt and processing of specimen, microscopy, chemistry assays, RPR/TPHA testing, hepatitis B serologic assays, cryopreservation, storage, and shipping of specimen, and is equipped with one biologic safety cabinets (Class II, Type A). All clinical testing and sample preparation/storage for this proposal will be performed in this laboratory, in accordance with current WHO and CDC biosafety guidelines. The URTC laboratory is licensed by the Kenya Medical Laboratory Technician and Technologist board (KMLTTB), as required by Kenyan law.</p>\n<p>\n <em>Computer: </em>NRHS has approximately 24 desktops that are networked within a LAN to three servers – an internal proxy email server that uses ADSL, a back-up server, and a data server. These are all guarded by a Sonic Firewall. Data stored are automatically downloaded and backed-up nightly. Wireless connection to the server is available throughout. There is a generator with an automatic switch and ample capacity in case of municipal power failures.</p>\n<p>\n <em>Office: </em>NRHS has 4 clinical rooms, 2 counseling rooms, an equipped laboratory, several office spaces and a conference room at the URTC in Kisumu. Its administrative offices are in the nearby United Mall with 2400 sq ft of space. There is space for Project Coordinators, an accountant and common space for Research Assistants. There is also office space available for visiting scientists and site visits for the PIs and co-investigators. There is additional storage space in an adjacent converted container and a large warehouse which is off the premises.</p>\n<p>\n Anza Mapema has 23 staff headed by a study coordinator Dancun Okal, BA, MPH(c). the staff comprise of 1 quality management officer, 2 clinical officers, 2 nurse counselors, 1 pharmaceutical technologist, 4 psychological counselors, 1 outreach coordinator, 2 tracers, 1 data clerk, 1 data management officer, 2 receptionists, 2 cleaners, 1 driver and 2 groundsmen. Additionally the study has 15 peer educators who are participants in the study but assist with tracing other participants.</p>\n
      • other_details_explanation<p>\n Kenya is the host country</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Maseno University Ethical Research Committee, initial approval 17-DEC-2014</p>\n<p>\n University of Illinois at Chicago IRB, initial approval 04-FEB-2015</p>\n<p>\n University of Washington IRB, initial approval 15-JAN-2015</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration4 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_stateYes
      • location_of_areaAnza Mapema Study Clinic
      • single_site_physical_addressAnza Mapema Clinic, Tom Mboya Estate, Dakar Road
      • single_site_contact_personDr Fredrick Odhiambo Otieno
      • single_site_telephone+254721759867
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site700
      • total_participants_worldwide700
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female0
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • 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_othersYes
      • subjects_others_specifyGay and Bisexual Men who have Sex with Men
      • investigator1_given_nameFredrick
      • investigator1_middle_nameOdhiambo
      • investigator1_family_nameOtieno
      • investigator1_qualificationPhD
      • investigator1_professional_addressNyanza Reproductive Health Society, UNIM Research and Training Centre, Inside Lumumba Sub County Hospital, Off Ondiek Highway
      • investigator1_telephone+254721759867
      • investigator1_emailfotieno@nrhskenya.org
      • organisations_transferred_No
      • number_participants700
      • notification
      • approval_date01-09-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-05-2017
      • 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)
      • modified2019-01-23 07:27:43
      • created2017-04-05 08:49:30
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id382
        • application_id603
        • given_nameFredrick
        • middle_nameOdhiambo
        • family_nameOtieno
        • qualificationPhD
        • professional_addressNyanza Reproductive Health Society, UNIM Research and Training Centre, Inside Lumumba Sub County Hospital, Off Ondiek Highway
        • telephone+254721759867
        • emailfotieno@nrhskenya.org
        • created2017-04-05 10:11:30
        • modified2017-04-24 07:59:51
    • SiteDetail(array)
      • 0(array)
        • id482
        • application_id603
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2017-04-05 10:11:30
        • modified2017-04-24 07:59:51
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id306
        • application_id603
        • sponsorNyanza Reproductive Health Society
        • sponsor_type(null)
        • contact_personDr Fredrick Odhiambo Otieno
        • addressNyanza Reproductive Health Society, UNIM Research and Training Centre, Inside Lumumba Sub County Hospital, Off Ondiek Highway
        • telephone_number+254572024065
        • fax_number
        • cell_number+254721759867
        • email_addressfotieno@nrhskenya.org
        • created2017-04-05 10:11:30
        • modified2017-04-24 07:59:51
  • 2(array)
    • Application(array)
      • id579
      • user_id63
      • trial_status_id4
      • abstract_of_study<p>\n <strong>Background</strong>; although Kenya has a well-organized National Tuberculosis Control Programme, the rate of TB disease remains among the highest in the world. The country is ranked 13th among the 22 TB high burden countries that constitute 80% of the global incidence of TB cases. Approximately 4 years ago, a new test called the Xpert MTB/Rif test became available for rapid and sensitive diagnosis of TB.</p>\n<p>\n <strong>Problem</strong>. To obtain additional performance data for a TB diagnostic that, in aggregate, covers a range of performance profiles suitable for the realities of tiered healthcare systems that include specimen testing at point of care as well as in more centralized laboratories.  To that end, this study expects to assess the accuracy and operational characteristics of the BD MAX assay, which is expected to be most suitable for use in central laboratories in which large numbers of specimens are tested and minimal operator hands-on time is desirable.</p>\n<p>\n <strong>Objectives;</strong> The primary objectives is to evaluate the performance of the BD MAX™ MDR-TB assay for the detection of <em>Mycobacterium tuberculosis</em> complex, and to determine whether <em>M. tuberculosis</em> complex detected is resistant to rifampin and to isoniazid from raw sputum or concentrated sputum sediments prepared from induced or expectorated sputa collected from patients with symptoms of pulmonary tuberculosis (TB) in a clinical setting.</p>\n<p>\n <strong>Methodology</strong>; Participants will be screened for TB symptoms and those with signs and symptoms will be consented and enrolled into the study.  Sputum specimens will be obtained from adults with signs/symptoms of tuberculosis who are enrolled prospectively into this study.  In addition, up to 250 existing de-identified sputum specimens will be shipped to study sites for in vitro laboratory testing.           </p>\n<p>\n One sputum specimen ≥3mls will be collected from each participant at the implementing sites within Kisumu and siaya counties after consenting and transported to KEMRI/CDC TB laboratory for processing using both this investigational test and standard tests including culture and standard Xpert. Data will be collected and analyzed using statistical packaged like STATA and SAS. It is expected that the results of this study will be able to improve on the accuracy and duration of MDR- TB diagnosis.</p>\n<p>\n <strong>Population</strong>: Sputum specimens will be obtained from up to 500 adults with signs/symptoms of tuberculosis who are enrolled prospectively into this study at the KEMRI site.  In addition, up to 250 existing de-identified sputum specimens will be shipped to KEMRI study site for in vitro laboratory testing. </p>\n<p>\n <strong>Sites</strong>:  This is a multicenter study.  Participant enrollment in Kenya will done at health facilities within Kisumu and siaya counties in western Kenya. Laboratory in vitro testing will occur at KEMRI/CDC TB laboratory at Kisian.</p>\n<p>\n <strong>Summary</strong>; The proposed study will assess the performance of BD MAX™ MDR-TB assay in clinical laboratories for MDR-TB case detection with rifampin and isoniazid resistance. Early analytical data for the BD MAX™ MDR-TB assay show promising results, but there is a need for additional performance data obtained in multiple settings of intended use and under rigorous clinical trial conduct.  This study will also assess accuracy and operational characteristics of the BD MAX™ MDR-TB assay in clinical laboratories in TB-endemic settings</p>\n
      • study_title<p align=\"center\">\n <strong>Multicenter Study of the Accuracy of the BD MAX™MDR-TB Assay for Detection of <em>M. tuberculosis Complex </em>and Mutations Associated with Resistance to Rifampin or Isoniazid</strong></p>\n
      • laymans_summary(null)
      • short_titleMulticenter Study of the Accuracy of the BD MAXâ„¢MDR-TB Assay
      • protocol_noECCT/17/05/01
      • version_no1.0
      • date_of_protocol04-01-2016
      • study_drugBD MAXâ„¢MDR-TB Assay
      • disease_conditionTuberculosis
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameBD MAXâ„¢MDR-TB Assay
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressEokeyo@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_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_applicant+254 710 602 786
      • declaration_date113-02-2017
      • declaration_principal_investigatorDr Kevin P Cain
      • declaration_date213-02-2017
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<h3>\n Inclusion Criteria</h3>\n<ul>\n <li>\n <h3>\n Age 18 years or above</h3>\n </li>\n <li>\n <h4>\n Provision of written informed consent</h4>\n </li>\n <li>\n <h4>\n Clinical suspicion of pulmonary TB (including cough ≥2 weeks and at least 1 other symptom typical of TB)</h4>\n </li>\n</ul>\n
      • principal_exclusion_criteria<h3>\n Exclusion Criteria</h3>\n<ul>\n <li>\n <h3>\n Receipt of more than 2 doses (2 days) of TB treatmentwithin 6 months prior to enrollment</h3>\n </li>\n</ul>\n
      • primary_end_points<h3>\n Primary</h3>\n<h3>\n Clinical sensitivity and specificity with 95% confidence intervals will be estimated for detection of <em style=\"font-size: 12px;\">M. tuberculosis</em><span style=\"font-size: 12px;\">complex comparing the BD MAX™ assay result to the Reference method result.</span></h3>\n<h3>\n Clinical sensitivity and specificity with 95% confidence intervals will be estimated for detection of rifampin resistance and isoniazid resistance comparing the BD MAX™ assay result to the Reference method resultfor those specimens found to be positive for<em style=\"font-size: 12px;\"> M. tuberculosis</em><span style=\"font-size: 12px;\"> complex.</span></h3>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • 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_specifyThis is a diagnostic trial
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n STAFF IN THIS STUDY: 1 PHARMACIST, 1 FULL-TIME NURSE, 1 PART TIME NURSE, 1 CO-ORDINATOR, 1 COMMUNITY MOBILISATION OFFICER, 1 QA MANAGER, OFFICERS, 1 QC OFFICER, 1 DATA MANAGER, 1 DATA OFFICER, 1 DATA SPECIALIST.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n SITE FACILITIES: CLINICAL TRIALS PHARMACY, BIO-SAFETY LEVEL 2 AND 3 TB LABORATORIES, LABORATORY FOR SAFETY PROFILE, ARRANGEMENT FOR IN AND OUT-PATIENT FACILITIES ATJARAMOGI OGINGA ODINGA TEACHING AND REFERRAL HOSPITAL</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u><strong>Profiles of key staff in TB Branch at KEMRI/CDC:</strong></u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u>Dr Samuel Gurrion Ouma Ngaywa</u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Position Coordinating PI</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Dr OUma is a Medical Doctor and Epidemiologist with 10 years clinical experience and 5 years clinical research experience. He has a Bachelors degree in Medicine and Bachelors degree in Surgery ( MbCHB)  from the University of Nairobi  and  a Masters in Public Health ( Epidemiology) – MPH from the University of Liverpool. He is a Principal investigator in 2 studies in KEMRI CGHR and a Co Investigator in numerous studies in KEMRI CGHR.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n His current responsibilities are : Administering protocol training to staff, leading studies as a Principal Investigator and Co Principal Investigator, supervising staff in a research setting and clinical setting, ensuring protocols are implemented in compliance with study protocol and regulatory ( local and International) requirements, triaging and managing study related medical emergencies, triaging and managing clinical trial participants  medical problems,  reading and interpreting chest x rays, source document development , development of site specific addenda for multicenter international protocols, safety reporting in clinical trials, SOP development, abstract and manuscript development and proposal writin</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u>Dr. Kevin Cain</u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong><u>Position: TB branch Technical advisor</u></strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Dr. Cain is the technical advisor the TB branch for KEMRI/CDC and PI for this study. Dr. Cain received his MD degree from the University of Pennsylvania School of Medicine in 2001. He then completed a 3 year residency training in internal medicine, is board certified in internal medicine, and is licensed in the state of Michigan. After completing internal medicine training in 2004, Dr. Cain joined CDC in Atlanta, where he completed 2 years of applied epidemiology training as an Epidemic Intelligence Service (EIS) officer with the International Research and Programs Branch of the Division of Tuberculosis Elimination. After completing EIS in 2006, he remained at CDC in the same branch. He became team lead for TB/HIV in 2008, and he was acting chief of the branch in late 2010 and early 2011 before accepting a position with CDC Kenya as the Chief of the TB Branch for KEMRI/CDC in Kisumu.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Dr. Cain has led a variety of epidemiologic studies during his time at CDC, including studies of TB among foreign-born persons in the United States and of TB screening and diagnosis in people with HIV. Dr. Cain has over 20 publications in peer-reviewed literature, including first-author publications in the New England Journal of Medicine and the Journal of the American Medical Association. He also has authored several editorial commentaries at the invitation of scientific journals, has given multiple presentations at international conferences, and has worked closely with World Health Organization on global and regional policy. He led the development of a revised framework for TB/HIV for WHO in the Western Pacific Region. Currently, he is the US representative to the technical advisory group for TB for WHO Western Pacific Region.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u>Lazarus Odeny</u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong><u>Position: Senior Data Manager</u></strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He holds the position of TB branch Senior Data Manager</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He has over 10 years of data management, biostatistics and epidemiology experience. He is currently registered for a doctor of science in Epidemiology (PhD) at the Erasmus University in Rotterdam, Netherlands.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He has held the following positions:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1.    Senior Data Analyst and Data manager – <strong>KEMRI/CDC</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2.    Senior Data manager – International Centre for Reproductive Health (<strong>ICRH</strong>)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3.    Data manager – <strong>KEMRI/CDC</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He is proficient in SAS, SPSS, EPIINFO, STATA, Microsoft office 2003 suite (Word, Excel, PowerPoint, Access), VFP, Visual CE for PDA, Microsoft visual basic, DOTNET framework, S-Plus, C + +, SQL, ISA firewall server administrator and SQL servers. All large studies conducted by the TB branch in the past several years have utilized electronic data collection and management, and this process has been designed and managed by Lazarus.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u>Rose Abwunza</u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong><u>Quality Assurance Manager</u></strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n She holds the position of QA manager since 2015 in the TB research branch.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A graduate of the University of Nairobi in <strong>Masters in Arts (project planning and management).</strong> she graduated in 2013.<strong> </strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The position of Quality Assurance (QA) in the TB research branch has allowed her to participate in several studies: 2 regulated epidemiological studies i.e. Adolescent Cohort study (an epidemiological study on TB prevalence and Incidence in adolescents), Infant Cohort study (an epidemiological study investigating the incidence of TB in Infants), and a TB vaccine study,  and other operations research studies and drug trials.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The QA duties include management of regulatory submissions, tracking of all annual approvals, management of the essential documents<strong>, </strong>safety and deviation tracking and reporting<strong>, </strong>quality control and verification of source documents and CRFs<strong>, </strong>preparation of study files for data collection<strong>, </strong>hosting monitoring and audit visits<strong>, </strong>corrective actions follow up and archiving of study documents .</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n She has gained relevant trainings and skills during her research experience which include:  Good Clinical Practice, trial site management as a study coordinator, trial site management as a study monitor (CRA), ethical aspects in clinical research, and epidemiology and biostatistics; all trainings were offered by the Vienna School of Clinical Research (VSCR). </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u>Dr. Victor Mudhune</u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong><u>Position: Clinical Trials Pharmacist</u></strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He holds the position of study pharmacist in the HIV research and TB branches and is the pharmacist for the TBTC drug trial. He previously worked as a hospital pharmacist.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n His major duties as a clinical trials pharmacist include:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1.    Coordination of all issues related to study drug/placebo supply and preparing all doses for administration and dispensing by the nurses.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2.    Maintaining appropriate records of the receipt and disposition of the study vaccine, placebos, benefit vaccine and inventory of all medicines.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3.    Monitoring and documenting cold chain maintenance for all study vaccines to ensure quality of the products is not compromised.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4.    Managing study participant randomization process and preparing the study vaccine/placebo doses for administration to study participants as per the study vaccine management manual.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 5.    Maintaining the blinding of the participant’s treatment assignment to investigators, study nurses, clinic staff and participant.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 6.    Maintaining the confidentiality of the participant, participant’s pharmacy file and the study drug/placebo accountability record.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 7.    Establishing a system to ensure that the participants sign an informed consent before dispensing the drugs and ensuring that the current IRB approved version of the protocol is adhered to in dispensing the drug/placebo.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 8.    Ensuring the security of all documents and investigational drug/placebo.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 9.    Preparing pharmacy related standard operating procedures ensuring they meet GCP, NIH and other regulatory requirements.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 10.  Following established departmental policies, procedures and objectives, continuous quality improvement objectives and safety, environmental and/or infection control standards.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 0.25in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 11.  Providing overall supervision to senior TB branch staff on pharmacy related activities.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 1in; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He has worked as a research pharmacist for the last 4.5 years as a research pharmacist and is trained in GCP, Human Subject Protection, NIH online training, and clinical trial management. He is currently training others in the same courses at the KEMRI/CDC field stations.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He has been involved in site preparations for the PAVE 100 trial, a DAIDS sponsored trial and in a completed study (the Kisumu Breastfeeding Study). He also functioned as backup pharmacist in a completed vaccine study (Rotavirus Vaccine Study).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He is the clinical trial pharmacist for the HPTN 052, a DAIDS sponsored trial, and the pharmacist to:  Aeras 402 vaccine trial (TB vaccine study), the TBTC drug trial and GSK MAL055/058 Vaccine trial.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u>Albert Ochieng Okumu</u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong><u>Position: Laboratory Manager</u></strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He holds the position of Laboratory Manager for the KEMRI/CDC, TB laboratory at the Kisian field station. His focus is on the quality and excellent performance of the KEMRI/CDC TB research laboratory. He has been able to receive into this laboratory study monitors, lab assessment visitors and auditors conducting assessments of the TB clinical trials at the site.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He has received and also coordinated trainings in: Good Clinical Laboratory Practice, participation in external quality assessment programmes and developed in house Quality Control systems.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He has worked previously with government health facilities in Kenya in different capacities, such as a laboratory technologist, government health facility laboratory in-charge and government laboratories district in-charge. His work with the Ministry of Health gave him experience in routine laboratory tests and procedures, laboratory diagnostics including in patients with TB and HIV of all ages.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n His initial research experience was at the Kenya Medical Research Institute, Centre for Microbiology Research, Kisumu, in an ‘Investigational New Drug’ HIV trial sponsored by the Gates foundation. This study was conducted for five years and it was implemented by Partners in Prevention (University of Washington). In his role in the study he was able to establish a functional clinical research laboratory. He also supported various sub- studies that conducted several laboratory assays for participants in microbicide studies such as: Female ViVaGel-USA, IPM (International partnerships for microbicides) of South Africa.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He has received trainings and skills in Good Clinical Laboratory Practice (GCLP) and Ethics (IAVI and Vienna School of Clinical Research), International shipping regulations (IATA, Mayo) and he has coordinated trainings in: GCLP, participation in external quality assessment programs and developed in-house Quality Control systems.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u>Janet Agaya</u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong><u>Position: Study Coordinator Tuberculosis Trials Consortium (TBTC) study</u></strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n She holds the position of study coordinator in the Tuberculosis Trials Consortium (TBTC) study</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n She is has worked previously as a Public Health officer at the Ministry of Health, Kenya and holds a Masters degree in Public Health. She has participated in many research projects in different capacities with products in reports, published and unpublished papers.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n She has successfully coordinated TB studies in KEMRI/CDC including TB prevalence surveys from 2005 to date. This has involved management of field activities for several TB research studies and working with people from different communities and cultural backgrounds.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n She has received training that is relevant to her work in research and this includes: Good Clinical Practice, Scientific Writing, Epidemiology, Research Ethics, Health Behavior and Education for Community Health Workers.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <u>Benard Owuor</u></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong><u>Position: TB branch Administrative Manager</u></strong></p>\n<p align=\"left\" font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p align=\"left\" font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n He holds the position of TB branch Administrative Manager. His qualifications include: MBA (finance), BBA (Accounting), CPA and Diploma in information technology and computer sciences.</p>\n<p align=\"left\" font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p align=\"left\" font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n His work experience in accounting, auditing and management covers 10 years at KEMRI/CDC and at 2 educational institutions. He also has 6 years experience as an administrator where he has been able to demonstrate: good leadership, organisational management, team-building skills, flexibility and strong communication skills.</p>\n<p align=\"left\" font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n In his capacity as administrative manager in the TB research branch, KEMRI/CDC he has been able to oversee financial management, organisational management and administrative tasks for several TB branch research studies, managing budgets of millions of dollars, and handling all reporting and auditing requirements for sponsors.</p>\n
      • other_details_explanation<p>\n The trial is being conducted in Kenya because Kenya is a TB endemic setting.</p>\n
      • other_details_regulatory_notapproved<p>\n Centers for Disease Control and Prevention-Seeking Reliance on KEMRI approval</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SCIENTIFIC AND ETHICS REVIEW UNIT-APPROVED ON 5TH JAN 2017</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted
      • estimated_durationApproximately 12 months
      • design_controlled_randomisedNo
      • design_controlled_openYes
      • design_controlled_single_blindYes
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyOnly the staff handling the IP will be blinded to the test results of the conventional methods
      • design_controlled_comparatorCulture and Standard Xper
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyWe intend to compare the results of the new assay to the standard approved tests
      • single_site_member_stateYes
      • location_of_areaKENYA MEDICAL RESEARCH INSTITIUTE
      • single_site_physical_addressKISIAN CAMPUS OFF BUSIA ROAD
      • single_site_contact_personKevin P Cain
      • single_site_telephone+254 710 602 786
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites
      • multi_country_listKisumu, Kenya; Cape Town, South Africa; Kampala, Uganda; Lima, Peru; Pune, India
      • data_monitoring_committeeNo
      • total_enrolment_per_siteUP TO 500
      • total_participants_worldwideUP TO 2000
      • 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_nameSAMUEL
      • investigator1_middle_nameGURRION
      • investigator1_family_nameOUMA
      • investigator1_qualificationMEDICAL DOCTOR
      • investigator1_professional_addressP.O BOX 1578 KISUMU, 40100
      • investigator1_telephone0722957050
      • investigator1_emailSouma@kemricdc.org
      • organisations_transferred_No
      • number_participantsUP TO 500
      • notification
      • approval_date20-08-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted16-06-2017
      • 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)
      • modified2018-07-02 08:52:44
      • created2017-01-17 11:28:48
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id375
        • application_id579
        • given_nameSAMUEL
        • middle_nameGURRION
        • family_nameOUMA
        • qualificationMEDICAL DOCTOR
        • professional_addressP.O BOX 1578 KISUMU, 40100
        • telephone0722957050
        • emailSouma@kemricdc.org
        • created2017-01-17 11:40:22
        • modified2017-06-16 08:28:35
    • SiteDetail(array)
      • 0(array)
        • id472
        • application_id579
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2017-01-17 11:40:22
        • modified2017-06-16 08:28:35
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id301
        • application_id579
        • sponsorBECTON DICKINSON $ COMPANY
        • sponsor_type(null)
        • contact_personMaunank Shah
        • address Johns Hopkins University School of Medicine 725 North Wolfe Street, PCTB Room 224 Baltimore, Maryland, USA 21205
        • telephone_numberTel:443-287-0401
        • fax_number
        • cell_numberTel:443-287-0401
        • email_addressmshah28@jhmi.edu
        • created2017-01-17 11:40:22
        • modified2017-06-16 08:28:35
  • 3(array)
    • Application(array)
      • id513
      • user_id336
      • trial_status_id4
      • abstract_of_study<p>\n The specific aim of the proposed study is to test the safety and feasibility (Phase 1) and preliminary efficacy (Phase 2) of a new low cost device (Odon Device) to deliver the fetus during prolonged second stage of labor. Although the focus of the proposed study is on the Odon Device as an alternative to available management options for complicated second stage of labour, other potential indications to be studied in the future could include use for assistance during normal delivery and prevention of infections acquired during delivery.</p>\n<p>\n This device may be potentially safer and easier to apply than forceps/vacuum extractor for assisted deliveries, and a safe alternative to some Caesarean sections. It has potential for wide application in resource poor settings even by mid-level providers. If proven safe and effective, the Odon Device will be the first innovation in operative vaginal delivery since the independent development of forceps and the vacuum extractor centuries ago. The Odon device could play a major role in improving intrapartum obstetric care in low resource settings by making possible effective management of intrapartum complications in facilities lacking surgical capacity and/or personnel adequately trained in the use of forceps and the vacuum extractor.</p>\n<p>\n Intrapartum complications are responsible for approximately half of all maternal deaths and two million stillbirth and neonatal deaths per year. Prolonged second stage of labor is associated with potentially fatal maternal complications such as hemorrhage and infection and is a major cause of stillbirth and newborn morbidity and mortality. Evidence indicates that the majority of intrapartum deaths in low-resource settings could be prevented through the introduction of innovative strategies that would increase accessibility of obstetric care (e.g., task shifting). Technological developments such as the Odon device that reduce the skill level and equipment required to provide quality obstetric care are clearly needed.      </p>\n<p>\n Currently, the three main options for managing prolonged second stage of labor are Cesarean section, forceps and vacuum extractor. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for cesarean section) and highly trained staff that are often not available in low resource settings. Even when these options are available, their use is associated with increased maternal and perinatal complications. Safe use of forceps requires very high-level training that is seldom available in low-resource settings. Use of the vacuum extractor is limited by the need for fairly complex equipment requiring maintenance, and it is contra-indicated in women who are HIV positive or with unknown HIV status.</p>\n<p>\n The Odon device is a low cost, easy to use technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby.  It may also protect the baby from intrapartum infection. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care in low resource settings. </p>\n<p>\n The Odon Device was invented by Mr Jorge Odon who holds an intellectual property patent. Mr Odon does not have a medical or biological research background and will participate in the proposed study only in relation to issues on device development.</p>\n<p>\n This study has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) as one of the Primary Registries in the WHO Registry Network. The registration number of this trial is ACTRN12613000141741.</p>\n<p>\n The Department of Reproductive Health and Research (HRP/RHR) at the World Health Organization (WHO) is the sponsor of the trial and performs overall coordination.</p>\n
      • study_title<p>\n Feasibility, safety and preliminary efficacy study of a new device (Odón  Device) for assisted vaginal delivery</p>\n
      • laymans_summary<p>\n The specific aim of the proposed study is to test the safety and feasibility (Phase 1) and preliminary efficacy (Phase 2) of a new low cost device (Odon Device) to deliver the fetus during prolonged second stage of labor. Although the focus of the proposed study is on the Odon Device as an alternative to available management options for complicated second stage of labour, other potential indications to be studied in the future could include use for assistance during normal delivery and prevention of infections acquired during delivery.</p>\n<p>\n This device may be potentially safer and easier to apply than forceps/vacuum extractor for assisted deliveries, and a safe alternative to some Caesarean sections. It has potential for wide application in resource poor settings even by mid-level providers. If proven safe and effective, the Odon Device will be the first innovation in operative vaginal delivery since the independent development of forceps and the vacuum extractor centuries ago. The Odon device could play a major role in improving intrapartum obstetric care in low resource settings by making possible effective management of intrapartum complications in facilities lacking surgical capacity and/or personnel adequately trained in the use of forceps and the vacuum extractor.</p>\n<p>\n Intrapartum complications are responsible for approximately half of all maternal deaths and two million stillbirth and neonatal deaths per year. Prolonged second stage of labor is associated with potentially fatal maternal complications such as hemorrhage and infection and is a major cause of stillbirth and newborn morbidity and mortality. Evidence indicates that the majority of intrapartum deaths in low-resource settings could be prevented through the introduction of innovative strategies that would increase accessibility of obstetric care (e.g., task shifting). Technological developments such as the Odon device that reduce the skill level and equipment required to provide quality obstetric care are clearly needed.      </p>\n<p>\n Currently, the three main options for managing prolonged second stage of labor are Cesarean section, forceps and vacuum extractor. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for cesarean section) and highly trained staff that are often not available in low resource settings. Even when these options are available, their use is associated with increased maternal and perinatal complications. Safe use of forceps requires very high-level training that is seldom available in low-resource settings. Use of the vacuum extractor is limited by the need for fairly complex equipment requiring maintenance, and it is contra-indicated in women who are HIV positive or with unknown HIV status.</p>\n<p>\n The Odon device is a low cost, easy to use technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby.  It may also protect the baby from intrapartum infection. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care in low resource settings. </p>\n<p>\n The Odon Device was invented by Mr Jorge Odon who holds an intellectual property patent. Mr Odon does not have a medical or biological research background and will participate in the proposed study only in relation to issues on device development.</p>\n<p>\n This study has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) as one of the Primary Registries in the WHO Registry Network. The registration number of this trial is ACTRN12613000141741.</p>\n<p>\n The Department of Reproductive Health and Research (HRP/RHR) at the World Health Organization (WHO) is the sponsor of the trial and performs overall coordination.</p>\n
      • short_titleOdón Device for assisted vaginal delivery
      • protocol_noECCT/17/04/01
      • version_noOdon device Protocol Phase I v8 June 2016
      • date_of_protocol01-06-2016
      • study_drugOdon device
      • disease_conditionDelivery process
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameOdon device
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresszahida@qureshi.co.ke
      • 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_countries1
      • 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_plan1
      • applicant_contractual_agreement1
      • declaration_applicantZahida Qureshi
      • declaration_date120-02-2017
      • declaration_principal_investigatorZahida Qureshi
      • declaration_date220-02-2017
      • placebo_presentNo
      • study_objectives<div>\n The main objective of the study is to evaluate the safety and feasibility, in terms of ease of application </div>\n<div>\n and successful delivery, of the BD Odonâ„¢ Device in assisting vaginal delivery in singleton term </div>\n<div>\n pregnancies during the second stage of labour.</div>\n<div>\n  </div>\n
      • principal_inclusion_criteria<div>\n Written informed consent obtained preferably during an antenatal care visit, and always before the initiation of labour. In centres where regular attendance of antenatal care visits might be limited or where no on-site visits are proposed, it is planned that women could be ask to consent during early labour (less than 4 cm dilatation) if not too distressed),</div>\n<div>\n 2. Woman attended at least one antenatal visit at 36 weeks of gestation or more,</div>\n<div>\n 3. Woman is able to read and fully understand the consent information,</div>\n<div>\n 4. Age ≥ 18 and less or equal to 35 years of age,</div>\n<div>\n 5. Singleton pregnancy,</div>\n<div>\n 6. Gestational age equal to or more than 37+0 weeks by best estimate according to local protocols,</div>\n<div>\n 7. Live fetus assessed by methods used according to local protocols,</div>\n<div>\n 8. Fully dilated cervix,</div>\n<div>\n 9. Ruptured membranes (spontaneous or artificial),</div>\n<div>\n 10. Any anterior occiput presentation,</div>\n<div>\n 11. Station level equivalent to 2 cm or more below the spines (e.g. station +2 or lower), or equivalent grading used in study sites,</div>\n<div>\n 12. Fetal heart rate pattern recorded by continuous fetal electronic monitoring meeting the following criteria:</div>\n<div>\n a. Stable baseline rate between 110 and 160 beats/min,</div>\n<div>\n b. normal short and long term variability,</div>\n<div>\n c. absence of late decelerations,</div>\n<div>\n 13. Slightly prolonged second stage of labour, defined as women who have been pushing for at least 30 minutes if nulliparous and 15 minutes if multiparous.</div>\n
      • principal_exclusion_criteria<div>\n Suspected or confirmed maternal infection: Suspected infection will be diagnosed if any of the following are present:</div>\n<div>\n i. Fever ≥ 38 ºC,</div>\n<div>\n ii. Foul smelling amniotic fluid.</div>\n<div>\n 2. More than 24 hours rupture of membranes at the time of delivery or timing of rupture of membranes unknown,</div>\n<div>\n 3. Meconium-stained amniotic fluid,</div>\n<div>\n 4. History of coagulation disorder,</div>\n<div>\n 5. Previous uterine surgery,Intrapartum haemorrhage,</div>\n<div>\n 7. Absolute cephalopelvic disproportion,</div>\n<div>\n 8. Known recto-vaginal-urethral Streptoccocus B Haemolyticcus colonization,</div>\n<div>\n 9. Known HIV positive women,</div>\n<div>\n 10. A history of allergy or previous adverse reaction to latex</div>\n<div>\n 11. Any other condition or circumstance that, in investigator’s opinion, would compromise the safety of the mother or the fetus.</div>\n
      • primary_end_points<p>\n Failure rate of device application</p>\n<div>\n delivery with forceps or vacuum extraction</div>\n<div>\n ï‚· Caesarean section</div>\n<div>\n ï‚· Episiotomy</div>\n<div>\n ï‚· Lacerations of the low genital tract (vulvar, vaginal)</div>\n<div>\n ï‚· Perineal lacerations</div>\n<div>\n ï‚· Cervical laceration</div>\n<div>\n ï‚· Uterine rupture</div>\n<div>\n ï‚· Pelvic haematoma</div>\n<div>\n ï‚· Perineal or vaginal haematoma</div>\n<div>\n ï‚· Postpartum haemorrhage as routinely assessed and defined at the study centres</div>\n<div>\n ï‚· Postpartum endometritis or other infection as reported by study centres</div>\n<div>\n ï‚· Blood transfusion</div>\n<div>\n ï‚· Maternal pain during insertion of the device, using a scale</div>\n<div>\n ï‚· Perineal pain after delivery</div>\n<div>\n ï‚· Maternal experience</div>\n<div>\n 3.3.3.2. Infant outcomes</div>\n<div>\n Incidence of:</div>\n<div>\n ï‚· Abnormal respiratory rate at 2 hours after birth</div>\n<div>\n ï‚· Birth trauma or injuries (skull fracture, caput succedaneum, cephalohaematoma, cutaneous facial lesions and facial palsy, extracranial haemorrhages, subgaleal haemorrhage, subaponeurotic haemorrhage, intracranial injuries)</div>\n<div>\n ï‚· Low Apgar Scores (less than 7 at 1st minute and less than 7 at 5th minute)</div>\n<div>\n ï‚· Any other measure of asphyxia at birth, if collected routinely</div>\n<div>\n ï‚· Admission to Neonatal Intensive Care Unit</div>\n<div>\n ï‚· Length of stay (> 7 days) in neonatal intensive care unit</div>\n<div>\n <div>\n ï‚· Retinal haemorrhage</div>\n <div>\n ï‚· Anaemia</div>\n <div>\n ï‚· Jaundice</div>\n <div>\n ï‚· Infection</div>\n <div>\n ï‚· Phototherapy</div>\n <div>\n ï‚· Fetal or neonatal death</div>\n</div>\n<p>\n  </p>\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_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyPhased trial in humans
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Staff</p>\n<p>\n Prof Zahida Qureshi MBChB MMed ObGyn- PI</p>\n<p>\n Dr Alfred Osoti MBChB MMed (ObGyn) MPH-CoPI</p>\n<p>\n Midwives (2) to be identfied</p>\n<p>\n Infraestructure</p>\n<p>\n Comprehensive emergency obstetric and newborn care available on-site</p>\n
      • other_details_explanation<p>\n The study wil be implemented in low-middle-income countries</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Kenyatta National Hospital University of Nairobi ERC</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration6 months
      • 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_stateYes
      • location_of_areaKenyatta National Hospital
      • single_site_physical_addressOff Ngong Road
      • single_site_contact_personZahida Qureshi
      • single_site_telephone00254733605140
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states3
      • number_of_sites
      • multi_country_listArgentina, South Africa, kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site20
      • total_participants_worldwide108
      • 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_male0
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameZahida
      • investigator1_middle_name
      • investigator1_family_nameQureshi
      • investigator1_qualificationMBChB MMed
      • investigator1_professional_addressDepartment of Obs and Gyn, University of Nairobi,PO Box 19676 Nairobi Kenya
      • investigator1_telephone00254733605140
      • investigator1_emailzahida@qureshi.co.ke
      • organisations_transferred_Yes
      • number_participants20
      • notification
      • approval_date22-06-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-08-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n This was a proposal for implementation of the WHO A65711 study in four hospitals in South AfricaThis was a proposal for implementation of the WHO A65711 study in one hospital at Kenyatta Hospital, in Nairobi. No woman was recruited under this study in Kenya.</p>\n<p>\n A prototype of the BD Odon device^TM  (BD, Franklin Lakes, NJ, USA) was used in one case in South Africa in 2017, before the company decided to stop supplying the devices to the WHO study and this trial was consequently terminated.One woman was recruited and application of the device failed.</p>\n<p>\n  </p>\n
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2020-08-14 11:45:02
      • created2016-07-01 14:46:35
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id337
        • application_id513
        • given_nameZahida
        • middle_name
        • family_nameQureshi
        • qualificationMBCHB MMed
        • professional_addressDepartment of Obs and Gyn, University of Nairobi,PO Box 19676 Nairobi Kenya
        • telephone00254733605140
        • emailzahida@qureshi.co.ke
        • created2016-07-06 06:48:19
        • modified2020-08-14 11:45:02
    • SiteDetail(array)
      • 0(array)
        • id399
        • application_id513
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-07-06 06:48:19
        • modified2020-08-14 11:45:02
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id267
        • application_id513
        • sponsorThe World Health Organization
        • sponsor_typeResearch Institution
        • contact_personMercedes Bonet
        • addressThe World Health Organization Headquarters
        • telephone_number004122 791 3347
        • fax_number
        • cell_number004122 791 3347
        • email_addressbonetm@who.int
        • created2016-07-06 06:48:19
        • modified2020-08-14 11:45:02
  • 4(array)
    • Application(array)
      • id598
      • user_id377
      • trial_status_id6
      • abstract_of_study<p>\n  </p>\n<table align=\"right\" border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"98%\">\n <tbody>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Protocol Title</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of GBT440 Administered Orally to Patients with Sickle Cell Disease</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Protocol Number</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n GBT440-031</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Sponsor </strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n Global Blood Therapeutics, Inc.<br />\n 400 East Jamie Court Suite #101<br />\n South San Francisco, CA  94080</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Study Drug</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p style=\"margin-left: 12.95pt;\">\n ·    GBT440 capsules or tablets, 300 mg each, administered orally</p>\n <p style=\"margin-left: 12.95pt;\">\n ·    Matching placebo, administered orally</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Number of Clinical Sites</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n The study will be conducted at approximately 75 international clinical sites.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%; height: 48px;\">\n <p>\n <strong>Number of Study Participants</strong></p>\n </td>\n <td style=\"width: 81.9%; height: 48px;\">\n <p>\n Approximately 340 total participants with Sickle Cell Disease (SCD), adults and adolescents (up to approximately 400) will be enrolled, as follows:</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 1</u></strong><strong>:</strong> Approximately 60 participants</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 2</u></strong><strong>:</strong> Up to approximately 90 participants; enrollment begins with participant #61 and ends when the Group 3 dose has been selected from the Group 1 Analysis</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 3</u></strong><strong>:</strong> At least 190 participants and up to 250 participants; enrollment begins when the Group 3 dose has been selected from the Group 1 Analysis</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%; height: 48px;\">\n <p>\n <strong>Treatment</strong></p>\n </td>\n <td style=\"width: 81.9%; height: 48px;\">\n <p style=\"margin-left: 12.95pt;\">\n <strong><u>Group 1</u></strong>: Participants will be randomized in a 1:1:1 ratio to receive GBT440 900 mg/day, GBT440 1500 mg/day, or matching placebo</p>\n <p style=\"margin-left: 12.95pt;\">\n <strong><u>Group 2</u></strong><strong>:</strong> Participants will be randomized in a 1:1:1 ratio to receive GBT440 900 mg/day, GBT440 1500 mg/day, or matching placebo</p>\n <p style=\"margin-left: 12.95pt;\">\n <strong><u>Group 3</u></strong><strong>:</strong> Participants will be randomized in a 1:1 ratio to receive GBT440 (900 mg/day or 1500 mg/day), or matching placebo</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Objectives</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p style=\"margin-left: -0.4pt;\">\n <strong>Primary</strong></p>\n <p>\n The primary objective is to assess the efficacy of GBT440 in adolescents and adults with SCD as measured by improvement in anemia.</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong>Secondary</strong></p>\n <p>\n The secondary objectives are to evaluate the effects of GBT440 compared to placebo on SCD symptom exacerbation and Total Symptom Score (TSS) from Patient Reported Outcome measurement (PRO), measures of anemia and hemolysis, and other clinical measures (e.g., vaso-occlusive crisis [VOC], Acute Chest Syndrome [ACS], hospitalization, red blood cell [RBC] transfusions, opioid use).</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong>Exploratory</strong></p>\n <p>\n The exploratory objectives are to evaluate the effects of GBT440 compared to placebo on the EuroQol EQ-5D-5L health questionnaire (EQ-5D-5L™), days missed from work/school, and measures related to SCD pathophysiology and to evaluate measures predictive of response to GBT440.</p>\n <p>\n <strong>Safety</strong></p>\n <p>\n The safety objectives are to assess the safety of GBT440 compared to placebo based on adverse events (AEs), clinical laboratory tests, physical examinations, and other clinical measures (e.g., discontinuations due to AEs, dose reductions).</p>\n <p>\n <strong>Pharmacokinetics </strong></p>\n <p>\n The pharmacokinetic (PK) objective is to assess the PK of GBT440 as evaluated by population PK analysis.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Study Design</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n <strong>STUDY DESIGN</strong></p>\n <p>\n This study is a randomized, placebo-controlled, double blind, parallel group, multicenter study of participants, age 12 to 65 years, with SCD (HbSS, HbSC,HbSβ0 thalassaemia or other Sickle Cell Syndrome variants) conducted in three groups of study participants, Groups 1, 2, and 3. The key purposes for each group are:</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong><u>Group 1</u>:</strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Dose selection: GBT440 dose (900 or 1500 mg) for further study.</p>\n <p style=\"margin-left: 36pt;\">\n ·      Final definition of endpoints for patient reported outcomes measure for the Main Population Analysis</p>\n <p style=\"margin-left: 36pt;\">\n ·      Electronic patient reported outcomes (ePRO) qualification for the Main Population Analysis</p>\n <p>\n <strong><u>Group 2</u>:</strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      To allow for a seamless transition from Group 1 to Group 3 by continuing enrollment and data collection in the study during the Group 1 treatment period and data analysis (referred to as Group 1 Analysis).</p>\n <p>\n <strong><u>Group 3</u>:</strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Establish efficacy and safety of GBT440 at the selected dose. The final data analysis set ( referred to as the Main Population) will include</p>\n <p style=\"margin-left: 108pt;\">\n §  Group 2 participants</p>\n <p style=\"margin-left: 144pt;\">\n ·      Assigned to placebo</p>\n <p style=\"margin-left: 144pt;\">\n ·      Assigned to the selected dose and</p>\n <p style=\"margin-left: 108pt;\">\n §  All Group 3 participants.</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong><u>Open Label Extension (under separate protocol)</u></strong></p>\n <p>\n Participants will be given the option to enroll in an open label extension study to receive GBT440 at the selected dose.</p>\n <p>\n The open label extension study will be available to eligible participants who:</p>\n <p style=\"margin-left: 22.1pt;\">\n ·      Were included in the Group 1 Analysis regardless of the treatment arm to which they were randomized.</p>\n <p style=\"margin-left: 22.1pt;\">\n ·      Were randomized in Group 2 to the dose not selected for Group 3.</p>\n <p style=\"margin-left: 22.1pt;\">\n ·      Were included in Group 3 and completed through end of treatment.</p>\n <p>\n The Study Schematic is provided in Figure 1, at the end of the Synopsis.</p>\n <p>\n <strong>Adolescent Participants </strong></p>\n <p>\n Initially only adult participants will be enrolled. Adolescent participants (12 to <18 years) will be included in enrollment/randomization when:</p>\n <p style=\"margin-left: 17.6pt;\">\n 1) Single dose PK data and modeling from Study GBT440-007 are available to confirm the appropriate dose for adolescent participants, and</p>\n <p style=\"margin-left: 17.6pt;\">\n 2) The Data Safety Monitoring Board (DSMB) has reviewed the safety data from at least 18 adults enrolled in this study of which at least 6 adults have received 1500 mg GBT440 for at least 4 weeks to confirm acceptable safety and tolerability before adolescents can be enrolled. Sites will be notified when adolescent participants can be enrolled in this study.</p>\n <p>\n At the time that these criteria are met, adolescents will begin to enroll (as early as in Group 1); a minimum of 50 adolescents will be included in the Main Population.</p>\n <p>\n <strong>Screening and Randomization</strong></p>\n <p>\n After signing the informed consent form (ICF), participant screening will include medical history, vital signs, electrocardiogram (ECG), complete physical exam (PE) including height and weight, blood chemistry including iron studies, hematology laboratory tests, serum pregnancy test for women, and urinalysis. The ePRO measure assessment must be completed for at least 75% of days of a 28-day Screening period. All screening procedures must be completed within 35 days before randomization. Laboratory tests will be performed by a central laboratory.</p>\n <p>\n <strong>Study DRUG INFORMATION</strong></p>\n <p>\n Participants receiving 1500 mg GBT440 will receive five 300 mg capsules or tablets, administered orally, once daily; participants receiving 900 mg GBT440 will receive three 300 mg capsules or tablets, and 2 placebo capsules or tablets administered orally, once daily. Participants randomized to placebo will receive 5 placebo capsules or tablets administered orally, once daily. Study drug may be taken with or without food. Participants in Group 1 must take their study drug in the mornings and must avoid high fat meals for 4 hours before and 4 hours after taking study drug. Group 2 and Group 3 participants may take study drug in the morning or evening, preferably at same time each day throughout the study ( Group 2 and Group 3 participants have no food restrictions/requirements).</p>\n <p>\n <strong>Dose Modifications</strong></p>\n <p>\n Guidelines for dose modification are provided in Table 1and Table 2at the end of the Synopsis. The Medical Monitor should be notified of all dose modifications within 72 hours. Details regarding study medication kit preparation and dispensation are provided in the Site Operations Manual.</p>\n <p>\n <strong>ANALYSIS GROUPS AND specifications </strong></p>\n <p>\n <strong>Analysis will be conducted on populations: </strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Group 1 Population</p>\n <p style=\"margin-left: 36pt;\">\n ·      Main Population: Group 2 (placebo and selected dose treatment arm only) and Group 3, combined</p>\n <p>\n <strong><u>Group 1</u>:  </strong></p>\n <p style=\"margin-left: 18pt;\">\n ·      When the 60^th participant reaches 12 weeks of treatment, data from the 60 participants will be unblinded, and a Group 1 Analysis will be conducted.</p>\n <p style=\"margin-left: 36pt;\">\n ·      The Group 1 Analysis will include PK, efficacy (primarily Hb response, ePRO endpoints, proportions of days with symptom exacerbation and change from Baseline in TSS), and safety endpoints, to inform the following for Group 3:</p>\n <p style=\"margin-left: 72pt;\">\n o   Dose selection will be performed: GBT440 dose (900 or 1500 mg) for further study.</p>\n <p style=\"margin-left: 72pt;\">\n o   Final definition of endpoints for patient reported outcomes measure for the Main Population Analysis</p>\n <p style=\"margin-left: 72pt;\">\n o   Electronic patient reported outcomes (ePRO) qualification for the Main Population Analysis.</p>\n <p style=\"margin-left: 72pt;\">\n o   Other potential modifications to the study: Allowable modifications will be to continue both doses if risk/benefit is unclear, to discontinue one of the doses if the second dose risk/benefit is clear, selection of intermediate dose (1200 mg) if the analysis suggests a better risk/benefit</p>\n <p style=\"margin-left: 36pt;\">\n ·      Data from Group 1 will not be combined with data from Groups 2 and 3 for the Main Population Analysis. </p>\n <p style=\"margin-left: 36pt;\">\n ·      The Sponsor may change or re-order the secondary endpoints for the Main Population Analysis based on the Group 1 Analysis and prior to unblinding of Main Population data.</p>\n <p style=\"margin-left: -0.4pt;\">\n <strong><u>Group 2</u>: </strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Group 2 includes study participants who enroll while the Group 1 Analysis is conducted.</p>\n <p style=\"margin-left: 36pt;\">\n ·      Randomization will continue 1:1:1 until a decision has been reached on the dose selected for use in Group 3.</p>\n <p style=\"margin-left: 36pt;\">\n ·      Once the GBT440 dose is selected for Group 3, participants who have received the non-selected GBT440 dose in Group 2 will be offered open label treatment under a separate protocol.</p>\n <p style=\"margin-left: 36pt;\">\n ·      Only participants in Group 2 assigned to placebo, and to the selected GBT440 dose for Group 3, will be included in the Main Population Analysis.</p>\n <p>\n <strong><u>Group 3</u>: </strong></p>\n <p style=\"margin-left: 36pt;\">\n ·      Group 3 participants will be randomized in a 1:1 ratio to receive the GBT440 selected dose or placebo. Group 3 will be included in the Main Population Analysis.</p>\n <p>\n <strong>BLINDING</strong></p>\n <p>\n This study is a double-blind study. The GBT440 and placebo capsules or tablets will be matched for shape, size, and color.</p>\n <p>\n For Group 1, with the exception of those noted below in Unblinding for Analysis, all individuals involved in the conduct of the study (i.e., site staff and study participants, contract research organization [CRO] personnel, Sponsor personnel) will be blinded to randomized treatment assignment.  </p>\n <p>\n For Groups 2 and 3, all individuals involved in the conduct of the study (i.e., site staff and study participants, Clinical CRO personnel, all Sponsor personnel) will be blinded to randomized treatment assignment. Drug Supply will remain unblinded throughout the study.</p>\n <p>\n <strong>Unblinding for Analysis</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 1</u></strong><strong>:</strong> To facilitate the Group 1 Analysis, certain Sponsor representatives and Sponsor designees will be unblinded to treatment assignments prior to and during the analysis (including the biostatistics CRO and external groups for bioanalytical PK/PD, and ePRO analyses). The blinded Sponsor study team members will be unblinded to the Group 1 Analysis results only after the Group 1 Analysis is complete.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 2</u>:</strong> Participants randomized to the non-selected dose will be unblinded and offered the option to enroll in an open label extension study. For the remaining Group 2 participants, unblinding to treatment assignment will occur after database lock for the Main Population Analysis.</p>\n <p style=\"margin-left: 12.95pt;\">\n <strong><u>Group 3</u>:</strong> Unblinding to treatment assignment will occur after database lock for the Main Population Analysis.</p>\n <p>\n <strong>Unblinding for Laboratory Test Assessment</strong></p>\n <p>\n Local laboratory tests including hematology laboratory tests may be used as needed per standard of care to manage AEs (such as hospitalization for VOC), and in these circumstances, the laboratory data may need to be unblinded.</p>\n <p>\n Because knowledge of certain laboratory assessments (Hb, hematocrit [Hct], RBC count, total and unconjugated bilirubin, and absolute and % reticulocyte count) may suggest the treatment assignment, these measurements will be redacted to the Investigator and monitored on a regular basis by the DSMB. Results of redacted laboratory tests will be communicated to the Investigator if a participant’s absolute reticulocyte count declines to <80 × 10⁸/L or Hb declines to <5.0 g/dL (but this does not require breaking of the treatment assignment blind). This is to ensure participant safety by allowing the Investigator to monitor for potential bone marrow suppression, as described in hydroxyurea (HU) monitoring guidelines (NHLBI 2014) (National Heart, Lung, and Blood Institute; NHLBI; 2014). All other laboratory assessments (not redacted) will be available to the Investigator. Anonymized laboratory results will be available to the Sponsor.</p>\n <p>\n <strong>Unblinding for Medical Need</strong></p>\n <p>\n If a medical condition should arise for which appropriate treatment cannot be decided without knowledge of the GBT440-031 study treatment assignment, the Investigator will contact the Sponsor to request permission to unblind. Pregnancy is considered a medical condition that requires unblinding. Upon written approval of the Sponsor, unblinding procedures will be followed as outlined in the Site Operations Manual and documented in the Investigator site file and the case report form (CRF).</p>\n <p>\n <strong>Data AND Safety Monitoring Board </strong></p>\n <p>\n An independent DSMB will monitor the safety and conduct of the trial. The DSMB will be comprised of medical and statistical representatives. The DSMB can provide recommendations to the Sponsor regarding stopping the study or discontinuing a treatment arm or otherwise modifying the study design or conduct.</p>\n <p>\n The DSMB will review:</p>\n <p style=\"margin-left: 36pt;\">\n ·       The Group 1 Analysis and provide an assessment of the benefit to risk ratio of the 900 mg and 1500 mg doses.</p>\n <p style=\"margin-left: 36pt;\">\n ·       Safety data from at least 18 adults enrolled in this study of which at least 6 adults have received 1500 mg GBT440 for at least 4 weeks to confirm acceptable safety and tolerability before adolescents can be enrolled. The sites will be notified when adolescent participants can be enrolled in this study.</p>\n <p style=\"margin-left: 36pt;\">\n ·       Safety data on a periodic basis as defined in the DSMB Charter.</p>\n <p>\n Sites will be informed of the DSMB recommendations only if the recommendations lead to changes in the study conduct.</p>\n <p>\n The composition, responsibilities, and other details of the DSMB will be described in the DSMB Charter.</p>\n <p>\n <strong>Safety Assessments </strong></p>\n <p>\n Participant safety and tolerability will be monitored during the study using standard measures, including physical examinations, vital signs (including blood pressure [BP] and pulse rate), 12 lead ECGs, safety laboratory tests, urinalysis, concomitant medication usage and AE monitoring. All laboratory tests (including during the screening period) will be performed through a central laboratory.</p>\n <p>\n Assessments will be performed at Screening, and prior to dosing (Baseline), and at defined times during the study. Assessments will include blood chemistry and hematology, GBT440 whole blood and plasma concentrations (for population PK analysis), erythropoietin levels, hemoglobin fetal (HbF) levels (Baseline, and End of Treatment [EOT]), physical examinations, ECGs, blood samples for biomarker testing, ePRO SCD Severity Measure (SCDSM), and eDiary. Once the participant initiates study drug treatment, assessments will be conducted every 2 weeks for the first 8 weeks, then every 4 weeks until end of study drug treatment. Safety assessments will be conducted at approximately 30 days after the last dose of study drug.</p>\n <p>\n Assessment of AEs will begin at the time of signing the ICF and will continue through the last study visit. AEs and laboratory values will be graded with National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (v4.03: June 14, 2010).</p>\n <p>\n Participants enrolled will complete the EQ-5D-5L™ at defined times during the study. EQ-5D-5L™ is a standardized instrument for use as a measure of health outcome; it provides a simple descriptive profile and a single index value for health status.</p>\n <p>\n <strong>Restrictions Regarding Concomitant Medications </strong></p>\n <p>\n GBT440 should be used with caution with CYP3A4 substrates with a narrow therapeutic index.</p>\n <p>\n The use of strong inducers of CYP2B6, CYP2C9, CYP2C19, and CYP3A4/CYP3A5 is prohibited. The use of herbal medications (e.g., St. John’s Wort) is not allowed.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%; height: 48px;\">\n <p>\n <strong>Duration of Study Participation</strong></p>\n </td>\n <td style=\"width: 81.9%; height: 48px;\">\n <p>\n <strong>Duration of Treatment</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 1</u>:</strong> Minimum duration is 12 weeks, maximum duration is 72 weeks or up to the completion of the Group 1 Analysis, whichever comes first.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 2</u>:</strong> Minimum duration is 2 weeks, maximum duration is 72 weeks.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 3</u>:</strong> Minimum duration is 24 weeks, maximum duration is 72 weeks.</p>\n <p>\n <strong>Duration of Study</strong></p>\n <p>\n Duration of study for an individual participant includes Screening (at least 28 days, but up to 35 days to account for Screening window flexibility), treatment for a minimum of 12 weeks and a maximum of 72 weeks, and an End of Study (EOS) visit at 4 weeks (± 7 days) after the last dose of study drug. From Screening through follow-up, total participation in this study for an individual participant may last from approximately 22 weeks to up to 81weeks. The minimum study duration is approximately 10 weeks (for participants in Group 2 enrolled at a dose not selected for Group 3). Participants will continue to be followed for efficacy and safety through at least the endpoint visit (Week 12 for Group 1 and Week 24 for the Main Population) regardless of treatment discontinuation.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Study Population</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n <strong>Inclusion Criteria</strong></p>\n <p style=\"margin-left: 18pt;\">\n 1.     Male or female study participants with sickle cell disease</p>\n <p style=\"margin-left: 37.5pt;\">\n ·      Documentation of SCD genotype (HbSS, HbSC, HbSβthalassemia or other sickle cell syndrome variants) may be based on history of laboratory testing or must be confirmed by laboratory testing during screening</p>\n <p style=\"margin-left: 18pt;\">\n 2.     Participants have had at least 1 episode of VOC in the past 12 months. For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis <strong>(</strong>for which there was no explanation other than VOC<strong>)</strong> which required prescription or healthcare professional‑instructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening)</p>\n <p style=\"margin-left: 18pt;\">\n 3.     Age 12 to 65 years</p>\n <p style=\"margin-left: 18pt;\">\n 4.     Hemoglobin (Hb) ≥6.0 and ≤10.5 g/dL during Screening</p>\n <p style=\"margin-left: 18pt;\">\n 5.     Absolute reticulocyte count and % reticulocyte count must be >1.5 × upper limit of normal (ULN) during Screening</p>\n <p style=\"margin-left: 18pt;\">\n 6.     For participants taking HU, the dose of HU (mg/kg) must be stable for at least 3 months prior to signing the ICF and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator</p>\n <p style=\"margin-left: 18pt;\">\n 7.     Participants must demonstrate 75% compliance with ePRO measure completion to be enrolled (participants will be given an ePRO device for at least 28 days during Screening; participants who are 60 to 74% compliant can re-screen once with Investigator approval; re‑screening is not allowed for participants who are <60% compliant)</p>\n <p style=\"margin-left: 18pt;\">\n 8.     Participants, who if female and of child bearing potential, are using highly effective methods of contraception from study start to 3 months after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 3 months after the last dose of study drug</p>\n <p style=\"margin-left: 18pt;\">\n 9.     Participant has provided documented informed consent or assent (the ICF must be reviewed and signed by each participant; in the case of pediatric participants, both the consent of the participant’s legal representative or legal guardian, and the participant’s assent must be obtained)</p>\n <p>\n <strong>Exclusion Criteria</strong></p>\n <p style=\"margin-left: 18pt;\">\n 1.     More than 10 VOCs within the past 12 months that required a hospital, emergency room or clinic visit</p>\n <p style=\"margin-left: 18pt;\">\n 2.     Female who is breast feeding or pregnant</p>\n <p style=\"margin-left: 18pt;\">\n 3.     Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 28 days of signing the ICF</p>\n <p style=\"margin-left: 18pt;\">\n 4.     Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to ICF )</p>\n <p style=\"margin-left: 18pt;\">\n 5.     Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × ULN</p>\n <p style=\"margin-left: 18pt;\">\n 6.     Participants with clinically significant bacterial, fungal, parasitic or viral infection which require therapy:</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. 
</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive</p>\n <p style=\"margin-left: 18pt;\">\n 6.     Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory) <30mL/min/1.73 m² or on chronic dialysis</p>\n <p style=\"margin-left: 18pt;\">\n 7.     History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non‑melanoma skin malignancy).</p>\n <p style=\"margin-left: 18pt;\">\n 8.     History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Unstable angina pectoris or myocardial infarction or elective coronary intervention</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Congestive heart failure requiring hospitalization</p>\n <p style=\"margin-left: 31.1pt;\">\n ·    Uncontrolled clinically significant arrhythmias</p>\n <p style=\"margin-left: 18pt;\">\n 10.  Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).</p>\n <p style=\"margin-left: 18pt;\">\n 11.  Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).</p>\n <p style=\"margin-left: 18pt;\">\n 12.  Inadequate venous access as determined by the Investigator/site staff.</p>\n <p style=\"margin-left: 18pt;\">\n 13.  Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may confound study interpretation, interfere with compliance, or preclude informed consent.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 18.1%;\">\n <p>\n <strong>Statistical Methods</strong></p>\n </td>\n <td style=\"width: 81.9%;\">\n <p>\n <strong>Study Endpoints</strong></p>\n <p>\n The endpoints listed below are for the <strong><u>Main Population</u></strong><u> <strong>Analysis</strong></u><strong> (</strong>Groups 2 and 3). The same endpoints will be evaluated for Group 1 participants at the Week 12 visit. In addition, for the Group 1 population, the primary efficacy measure is evaluated as two endpoints (details are provided in Section 10.2).</p>\n <p>\n <strong>Primary Endpoint</strong></p>\n <p>\n Increase in Hb >1 g/dL from Baseline to Week 24. Participant is responder if Week 24 Hb is >1 g/dL compared to Baseline.</p>\n <p>\n <strong>Secondary Endpoints</strong></p>\n <p>\n The first four endpoints are alpha-controlled.</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    Proportion of days with SCD symptom exacerbation during the first 24 weeks of treatment. This is the first-rank secondary endpoint.</p>\n <p style=\"margin-left: 13.1pt;\">\n •    Change from Baseline to Weeks 21–24 in the SCDSM TSS; for each participant, the TSS will be computed as follows: The Baseline TSS is the average of the score during the 28-day Screening period; during the treatment period, the TSS is the average score each 4-week period on treatment. The 4-week periods are Weeks 1–4, 5–8, 9–12, 13–16, 17–20, and 21–24 (and follows similarly for participants whose participation exceeds 24 weeks). This is the second-rank secondary endpoint.</p>\n <p style=\"margin-left: 13.1pt;\">\n •    Normalization of reticulocyte count at Week 24 (% reticulocytes <1.5 × ULN weeks)</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    VOC during the treatment period is defined as:</p>\n <p style=\"margin-left: 13.1pt;\">\n A composite of acute painful crisis or ACS and includes the following:</p>\n <p style=\"margin-left: 35.6pt;\">\n o   Moderate to severe pain lasting at least 2 hours</p>\n <p style=\"margin-left: 35.6pt;\">\n o   No explanation other than VOC</p>\n <p style=\"margin-left: 36pt;\">\n o   Requires oral or parenteral opioids, ketorolac, or other analgesics prescribed or directed by a healthcare professional</p>\n <p style=\"margin-left: 36pt;\">\n o   Must be documented in patient medical record that the patient was seen, or contacted the physician, within 1 day of the event. The event may take place in a medical setting (hospital, clinic, emergency room)</p>\n <p style=\"margin-left: 36pt;\">\n o   May include episodes of ACS (ACS is defined as an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray</p>\n <p style=\"margin-left: 15pt;\">\n ·     Rate of hospitalization for VOC during the treatment period</p>\n <p style=\"margin-left: 15pt;\">\n ·     Change from Baseline to 24 weeks in hemolysis and related measures: % reticulocytes, unconjugated bilirubin, Hb, dense RBCs</p>\n <p style=\"margin-left: 15pt;\">\n ·     Time to first ACS during the treatment period</p>\n <p style=\"margin-left: 15pt;\">\n ·     Time to first RBC transfusions during the treatment period</p>\n <p style=\"margin-left: 15pt;\">\n ·     Rate of opioid use, calculated as the proportion days that opioids were used each 4‑week period as recorded in an eDiary</p>\n <p style=\"margin-left: 15pt;\">\n ·     Length of hospitalization for VOC</p>\n <p>\n <strong>Exploratory Endpoints</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n ·    Change in health status compared to Baseline utilizing the EQ-5D-5L™</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    School and work attendance as measured in an eDiary. The rate of missed school and work days for each participant will be calculated as the proportion of days that school or work was missed every 4 weeks</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    Change from Baseline to 24 weeks in measures related to SCD pathophysiology, including lactate dehydrogenase (LDH), carboxyhemoglobin, glycated Hb Soluble P‑selectin, VCAM, ICAM, E-Selectin (and other exploratory measures that may be related to disease activity), urine albumin to creatinine ratio, serum cystatin C, Hb distribution width, RBC deformability (to be assessed at select centers), RBC phosphatidylserine expression (to be assessed at select centers), and TR jet velocity as assessed by echocardiography (to be assessed at select centers)</p>\n <p style=\"margin-left: 13.1pt;\">\n ·    Resolution of jaundice at Week 24 (total bilirubin >2 × ULN at Baseline and ≤2 × ULN at 24 weeks)</p>\n <p>\n <strong>Safety Endpoint</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n ·    AEs, clinical laboratory tests, physical examinations, and vital signs</p>\n <p>\n <strong>Pharmacokinetic Endpoint</strong></p>\n <p style=\"margin-left: 13.1pt;\">\n ·    PK of GBT440 as evaluated by population PK analysis using nonlinear mixed effects modeling</p>\n <p>\n <strong>Sample Size</strong></p>\n <p>\n The sample size for the study is estimated to be approximately 340 participants (up to approximately 400 participants).</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 1</u></strong><strong>:</strong> Approximately 60 participants will be randomized 1:1:1 to GBT440 900 mg, 1500 mg, or placebo.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 2</u></strong><strong>:</strong> Up to approximately 90 participants will be randomized 1:1:1 to GBT440 900 mg, 1500 mg, or placebo.</p>\n <p style=\"margin-left: 13.1pt;\">\n <strong><u>Group 3</u>:</strong> At least 190 participants and up to 250 participants will be randomized 1:1 to GBT440 at the selected dose or placebo.</p>\n <p>\n <strong>Sample Size for Group 1</strong>:</p>\n <p>\n The primary efficacy measure , Hb, will be evaluated as 2 endpoints:</p>\n <p style=\"margin-left: 17.3pt;\">\n ·       as change from Week 12 to Baseline (primary)</p>\n <p style=\"margin-left: 17.3pt;\">\n ·       as a responder endpoint (change from Week 12 to Baseline >1 g/dL)</p>\n <p>\n For the endpoint of change from Baseline in Hb, power calculations assume a mean treatment effect of 0.8 g/dL (GBT440 at either dose, minus placebo), the placebo change from Baseline is equal to 0, a per-group standard deviation (SD) of 0.6 g/dL. With N = 20 participants per arm, the power exceeds 95% of detecting a difference between either GBT440 arm (900 mg or 1500 mg) versus placebo. Power is calculated for the t-test and assumes that the data are normally distributed. The estimates of 0.8 g/dL and 0.6 g/dL for the treatment effect and SD, respectively, are based on data at Day 90 from Cohorts 16 and 17 from the GBT440-001 study.</p>\n <p>\n For the responder endpoint at Week 12, the GBT440 dose arms will be pooled. Assuming responder proportions of 35% and 5% for GBT 440 (N = 40 after pooling data from the 900 and 1500 mg groups) and placebo (N = 20), respectively, the power with Fisher’s exact test at a two-sided alpha = 0.05 is 80%.</p>\n <p>\n <strong>Sample Size for the Main Population Analysis: </strong></p>\n <p>\n The Main Population Analysis consists of Group 2 participants (estimated to be approximately 60, which includes approximately 30 selected GBT440 dose and 30 placebo patients) and Group 3 participants (minimum 190 patients and maximum 250 patients) for a total of 250 (minimum) to 310 (maximum).</p>\n <p>\n For the Hb responder endpoint at Week 24, power exceeds 95% based on Fisher’s exact test and a two-sided alpha of 0.05, assuming a 35% and 5% response rate for GBT440 and placebo. A sample size larger than required for an adequately powered primary endpoint was selected for the safety database. The sample size for the primary and ePRO secondary endpoints for the Main Population Analysis will be re‑estimated from the Group 1 Analysis, and if necessary, will be increased up to a maximum of 310 participants to ensure adequate power for the first key secondary endpoint (proportion of days with SCD symptom exacerbation). The estimation will not require an alpha adjustment because data from the Group 1 Analysis will not be included in the Main Population Analysis .</p>\n <p>\n <strong>Stratification</strong></p>\n <p>\n At the time of randomization, participants will be stratified for HU use (yes/no), geographic region (US, Europe, Other), and age (adolescent, 12 to <18 years, and adults, 18 to 65 years).</p>\n <p>\n <strong>Efficacy Population and Analysis</strong></p>\n <p>\n For each population, efficacy analysis will be performed on the Intent to Treat (ITT) population which includes all randomized participants.</p>\n <p>\n The Group 1 Analysis will determine the GBT440 dose selected, and determine any further modifications to the study. There will no adjustment for multiplicity for the Group 1 population. If both GBT440 dose groups are selected in the Main Population Analysis, the comparisons will be of each GBT440 dose versus placebo, and will be adjusted for multiplicity via gatekeeping procedures outlined in the SAP.</p>\n <p>\n <strong>Group 1 and Main Population Analysis</strong></p>\n <p>\n <strong>Primary Endpoint:</strong></p>\n <p>\n Hb Week 12 change from Baseline will be analyzed with a mixed effect repeated measures model (MMRM). The model will include terms for treatment, time, and treatment by time interaction. An unstructured covariance matrix will be used.</p>\n <p>\n This analysis will be performed for the Group 1 Analysis: The comparison of treatments at Week 12 for each GBT440 dose versus placebo; the data beyond Week 12 will be presented descriptively.</p>\n <p>\n This analysis will be performed for the Group 1 Analysis and Main Population Analysis: The Hb responder endpoint will be analyzed by the Cochran‑Mantel‑Haenszel (CMH) test for each GBT440 dose versus placebo.</p>\n <p>\n <strong>Secondary Endpoints:</strong></p>\n <p>\n Where applicable, the Group 1 and Main Population will be analyzed with respect to their endpoint visit which is Week 12 for Group 1 and Week 24 for the Main Population. Analyses for Group 1 and the Main Population will be summarized beyond the endpoint visit. For example, for Group 1, proportion of days with SCD symptom exacerbation and change from Baseline in TSS will be summarized for visits after the endpoint visit, including Week 24.</p>\n <p>\n The proportion of days with SCD exacerbation during the first 12 weeks of treatment will be analyzed by a fixed effects linear model.</p>\n <p>\n Change from Baseline in the TSS will be analyzed with an MMRM.</p>\n <p>\n Normalization of reticulocyte count will be analyzed by the CMH test.</p>\n <p>\n The rate of VOC and rate of hospitalization due to VOC will be analyzed by the CMH row means scores test.</p>\n <p>\n The plan for the Main Population Analysis will be described in further detail in the Statistical Analysis Plan (SAP) after results from the Group 1 Analysis become available and before unblinding the Main Population Analysis.</p>\n <p>\n <strong>Missing Data:</strong> Proportion of participants with missing data for the primary and key secondary efficacy endpoints will be summarized by treatment group for study scheduled visits. Handling of missing data for analysis is described in the body of the protocol. The general rule is assigning a worst score for missing data due to hospitalization for VOC, and a worst score for RBC transfusions regardless of whether or not data are missing.</p>\n <p>\n <strong>Safety Population and Analysis (Group 1 and Main Population)</strong></p>\n <p>\n The Safety Population is defined as all randomized participants who have received at least one dose of study medication. Participants will be analyzed based on medication received.</p>\n <p>\n Data for participants who provide eDiary data but discontinue treatment will be included in the analysis. Descriptive statistics for healthcare utilization will be summarized in a separate report.</p>\n <p>\n The incidence of treatment-emergent adverse events (TEAEs) will be tabulated by System Organ Class (SOC), preferred term, severity, and relationship to study drug. AEs that are considered to be related to study drug by the Investigator will be summarized. Changes in laboratory parameters and vital signs over time will be summarized.</p>\n <p>\n Demographics (age, sex, ethnicity, and race) and Baseline characteristics (height and weight) will be summarized by treatment and overall medical history will be provided in a data listing.</p>\n <p>\n Descriptive summaries will be provided for AEs, laboratory tests (hematology, serum chemistry, and coagulation), and vital signs (BP and pulse rate).</p>\n <p>\n <strong>Pharmacokinetics Population and Analysis (Group 1 and Main Population)</strong></p>\n <p>\n The PK Population will consist of all participants who receive active study drug and have at least one measured concentration at a scheduled PK time point after the start of dosing. If any participants are found to be noncompliant with respect to dosing or have incomplete data, protocol violations, or clinical events that affect PK, a decision will be made on a case-by-case basis as to their inclusion in the analysis. Participants in this population will be used for all PK summaries.</p>\n <p>\n Population PK analyses using nonlinear mixed effects modeling will be performed to characterize GBT440 PK in plasma, if applicable, or whole blood. The influence of demographic covariates (such as body weight, age, gender) on GBT440 PK parameters (i.e., clearance [CL] and volume of distribution) will be investigated. If appropriate, the GBT440 PK data may be pooled with PK data from other studies.</p>\n <p>\n Summary statistics of PK parameters for whole blood, plasma, and RBCs will be presented including means, geometric means, SD, and coefficient of variation (CV), medians, and ranges.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • study_title<p>\n A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of GBT440 Administered Orally to Patients With Sickle Cell Disease</p>\n
      • laymans_summary<div>\n Sickle cell disease (SCD) is an inherited disorder caused by a point mutation in the β-globin gene leading to formation of sickle hemoglobin (HbS). SCD predominantly occurs in individuals whose ancestors originated from sub-Saharan Africa, Spanish speaking regions of the Western Hemisphere (South America, Caribbean, and Central America); Saudi Arabia; India; and Mediterranean countries including Turkey, Greece, and Italy. SCD is the most common single gene</div>\n<div>\n disorder in African Americans. A primary and obligatory event in the molecular pathogenesis of SCD is the polymerisation of deoxygenated HbS and the resultant sickling of red blood cells (RBCs). SCD is characterized by hemolytic anemia and vaso-occlusion leading to progressive end-organ damage with a clinical course of life-long pain, disability, and early death. Management strategies for SCD have evolved very slowly, and treatment of SCD remains a serious unmet medical need. Hydroxyurea (HU) is the only approved therapy for SCD and is indicated to reduce the frequency of painful crisis requiring visiting a medical facility, although it has a minimal effect on the severe burden of daily pain (Smith 2011). HU is limited by its side effect profile, poor patient adherence, variable patient responses, and concerns of long-term toxicity. In addition to HU treatment, blood transfusions are used in this patient population to alleviate symptomatic anemia and to prevent certain SCD complications (especially cerebrovascular complications). Attaining anti-sickling activity by blood transfusions has its own limitations: the treatments are expensive, not uniformly accessible and accompanied by risks (Wahl 2009) (Platt 1996). The only curative treatment is bone marrow transplantation from a histocompatible donor, an option that has been available since the 1990s (Platt 1996), but bone marrow transplantation carries significant risks and</div>\n<div>\n is associated with a ~5% mortality rate. Despite the current standard of care, including HU, blood transfusion, and palliative therapy for acute attacks, patients with SCD continue to suffer serious morbidity and premature mortality (Steinberg 2003). To date, no drugs have been approved that specifically and directly target HbS polymerization, the underlying mechanism of SCD. There is a significant unmet need in SCD for new mechanism based,</div>\n<div>\n preventive, and potentially disease-modifying therapies. Because oxyhemoglobin is a potent inhibitor of HbS, allosteric modification of Hb to increase the</div>\n<div>\n proportion of oxyhemoglobin is a promising strategy to achieve inhibition of HbS in all RBCs (Noguchi 1988). Prior experimental drugs and approaches (discontinued due to poor pharmaceutical properties or off-target toxicity) have provided proof of concept for the Hb modification approach by</div>\n<div>\n demonstrating an increase in oxyhemoglobin, a decrease in clinical biomarkers of hemolysis, and an improvement in incidence of vaso-occlusive crisis (VOC) (Keidan 1986; Arya 1996; Deiderich 1976). Global Blood Therapeutics (GBT) has developed GBT440, a small molecule allosteric modulator of</div>\n<div>\n <div>\n Hb oxygen affinity, for the treatment of SCD. GBT440 is administered orally. The mechanism of action of GBT440 involves inhibition of HbS polymerisation by increasing the affinity of Hb for oxygen. Hb exists in both a relaxed (R) and a tense (T) state with high and low affinity for oxygen, respectively (Eaton 1999). Upon binding to HbS, GBT440 effectively maintains a targeted fraction of HbS in the R state. Hb S molecules that are in the R (oxygenated) state are</div>\n <div>\n <div>\n potent inhibitors of HbS polymerisation and, conversely, only deoxygenated HbS is capable o polymerizing to create sickling of RBCs. Because GBT440 binds to the Hb α chain, its effects on the oxygen equilibrium curves (OECs) are similar in normal and sickle blood. Nonclinical data, data from prior experimental Hb modifying agents, and genetic data from humans with hereditary persistence of fetal Hb (HPFH) and high affinity Hb mutations demonstrate that a target of modifying 20 to 30% of Hb molecules and possibly as low as 10% should be sufficient to inhibit sickling without impairing tissue oxygen delivery (Akinsheye 2011; Perrine 1972).</div>\n <div>\n Because of its mechanism of action as direct HbS polymerization inhibitor, GBT440 has the potential to be a chronic, preventive, disease modifying therapy for SCD.</div>\n </div>\n</div>\n<p>\n  </p>\n
      • short_titleHOPE Sickle Cell Disease Clinical Study
      • protocol_noECCT/17/03/05
      • version_noAmendment 1
      • date_of_protocol09-11-2016
      • study_drugGBT440
      • disease_conditionSickle Cell Disease
      • 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_nameGBT440
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressbernadette.kimotho@quintilesims.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries1
      • 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_plan0
      • applicant_contractual_agreement0
      • declaration_applicantBernadette Gathoni Kimotho (Clinical Researc Associate, Quinitles)
      • declaration_date120-03-2017
      • declaration_principal_investigatorProf Jessie Nyokabi Githanga
      • declaration_date216-03-2017
      • placebo_presentYes
      • study_objectives<div>\n Primary</div>\n<div>\n The primary objective is to assess the efficacy of GBT440 in adolescents and adults with SCD as measured by improvement in anemia.</div>\n<div>\n  </div>\n<div>\n Secondary</div>\n<div>\n The secondary objectives are to evaluate the effects of GBT440 compared to placebo on SCD symptom exacerbation and Total Symptom Score (TSS) from Patient</div>\n<div>\n Reported Outcome measurement (PRO), measures of anemia and hemolysis, and other clinical measures (e.g., vaso-occlusive crisis [VOC], Acute Chest Syndrome</div>\n<div>\n [ACS], hospitalization, red blood cell [RBC] transfusions, opioid use).</div>\n<div>\n  </div>\n<div>\n Exploratory</div>\n<div>\n The exploratory objectives are to evaluate the effects of GBT440 compared to placebo on the EuroQol EQ-5D-5L health questionnaire (EQ-5D-5L™), days missed</div>\n<div>\n from work/school, and measures related to SCD pathophysiology and to evaluate measures predictive of response to GBT440.</div>\n<div>\n  </div>\n<div>\n <div>\n Safety</div>\n <div>\n The safety objectives are to assess the safety of GBT440 compared to placebo based on adverse events (AEs), clinical laboratory tests, physical examinations, and other clinical measures (e.g., discontinuations due to AEs, dose reductions).</div>\n <div>\n  </div>\n <div>\n <div>\n Pharmacokinetics</div>\n <div>\n The pharmacokinetic (PK) objective is to assess the PK of GBT440 as evaluated by</div>\n <div>\n population PK analysis.</div>\n </div>\n <div>\n  </div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n <strong>Inclusion Criteria</strong></p>\n<p style=\"margin-left: 18pt;\">\n 1.     Male or female study participants with sickle cell disease</p>\n<p style=\"margin-left: 37.5pt;\">\n ·      Documentation of SCD genotype (HbSS, HbSC, HbSβthalassemia or other sickle cell syndrome variants) may be based on history of laboratory testing or must be confirmed by laboratory testing during screening</p>\n<p style=\"margin-left: 18pt;\">\n 2.     Participants have had at least 1 episode of VOC in the past 12 months. For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis <strong>(</strong>for which there was no explanation other than VOC<strong>)</strong> which required prescription or healthcare professional‑instructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening)</p>\n<p style=\"margin-left: 18pt;\">\n 3.     Age 12 to 65 years</p>\n<p style=\"margin-left: 18pt;\">\n 4.     Hemoglobin (Hb) ≥6.0 and ≤10.5 g/dL during Screening</p>\n<p style=\"margin-left: 18pt;\">\n 5.     Absolute reticulocyte count and % reticulocyte count must be >1.5 × upper limit of normal (ULN) during Screening</p>\n<p style=\"margin-left: 18pt;\">\n 6.     For participants taking HU, the dose of HU (mg/kg) must be stable for at least 3 months prior to signing the ICF and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator</p>\n<p style=\"margin-left: 18pt;\">\n 7.     Participants must demonstrate 75% compliance with ePRO measure completion to be enrolled (participants will be given an ePRO device for at least 28 days during Screening; participants who are 60 to 74% compliant can re-screen once with Investigator approval; re‑screening is not allowed for participants who are <60% compliant)</p>\n<p style=\"margin-left: 18pt;\">\n 8.     Participants, who if female and of child bearing potential, are using highly effective methods of contraception from study start to 3 months after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 3 months after the last dose of study drug</p>\n<p>\n  </p>\n<p style=\"margin-left: 18pt;\">\n 9.     Participant has provided documented informed consent or assent (the ICF must be reviewed and signed by each participant; in the case of pediatric participants, both the consent of the participant’s legal representative or legal guardian, and the participant’s assent must be obtained)</p>\n
      • principal_exclusion_criteria<p>\n <strong>Exclusion Criteria</strong></p>\n<p style=\"margin-left: 18pt;\">\n 1.     More than 10 VOCs within the past 12 months that required a hospital, emergency room or clinic visit</p>\n<p style=\"margin-left: 18pt;\">\n 2.     Female who is breast feeding or pregnant</p>\n<p style=\"margin-left: 18pt;\">\n 3.     Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 28 days of signing the ICF</p>\n<p style=\"margin-left: 18pt;\">\n 4.     Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to ICF )</p>\n<p style=\"margin-left: 18pt;\">\n 5.     Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × ULN</p>\n<p style=\"margin-left: 18pt;\">\n 6.     Participants with clinically significant bacterial, fungal, parasitic or viral infection which require therapy:</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed. 
</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive</p>\n<p style=\"margin-left: 18pt;\">\n 7.     Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory) <30mL/min/1.73 m² or on chronic dialysis</p>\n<p style=\"margin-left: 18pt;\">\n 8.     History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non‑melanoma skin malignancy).</p>\n<p style=\"margin-left: 18pt;\">\n 9.     History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Unstable angina pectoris or myocardial infarction or elective coronary intervention</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Congestive heart failure requiring hospitalization</p>\n<p style=\"margin-left: 31.1pt;\">\n ·    Uncontrolled clinically significant arrhythmias</p>\n<p style=\"margin-left: 18pt;\">\n 10.  Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).</p>\n<p style=\"margin-left: 18pt;\">\n 11.  Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).</p>\n<p style=\"margin-left: 18pt;\">\n 12.  Inadequate venous access as determined by the Investigator/site staff.</p>\n<p>\n  </p>\n<p style=\"margin-left: 18pt;\">\n 13.  Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may confound study interpretation, interfere with compliance, or preclude informed consent.</p>\n
      • primary_end_points<p>\n  </p>\n<p>\n The primary objective is to assess the efficacy of GBT440 in adolescents and adults with SCD as measured by improvement in anemia.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic1
      • 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<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 729px; height: 872px;\">\n <tbody>\n <tr>\n <td>\n SITE</td>\n <td>\n STAFF</td>\n <td>\n Facilities</td>\n <td>\n Experience</td>\n </tr>\n <tr>\n <td>\n Gertrude's Children's Hospital</td>\n <td>\n <p>\n PI - Prof Jessie Githanga (Mmed Path)</p>\n <p>\n Sub -I/SCC - Dr Jaspreet Gharial (Mmed Paeds)</p>\n <p>\n Pharmacist - Dr Monica Mirigo(Bpharm)</p>\n <p>\n Lab Technologist - Penina Chege</p>\n </td>\n <td>\n <p>\n Consultation Rooms</p>\n <p>\n Hospitalization facilities</p>\n <p>\n Air conditioned Pharmacy with temperature montoring</p>\n <p>\n Laboratory</p>\n <p>\n Emergency Trolley and ICU</p>\n <p>\n Phone and internet access</p>\n <p>\n  </p>\n </td>\n <td>\n <p>\n PI and Staff have experience conducting Randomized clinical trials in the sickle cell therapeutic area. The site has previously conducted two phase 3 clinical trials in sickle cell disease.</p>\n </td>\n </tr>\n <tr>\n <td>\n Strathmore University Medical Center</td>\n <td>\n <p>\n PI - Dr Bernhards Ogutu (MMed Paeds)</p>\n <p>\n Sub-I - Dr Anastacia Omoding (MBCHB)</p>\n <p>\n Investigator - Dr Elizabeth Juma (MBCHB)</p>\n <p>\n SCC - Amina Salim</p>\n </td>\n <td>\n <p>\n Consultation Rooms</p>\n <p>\n Emergency Trolley</p>\n <p>\n Pharmacy</p>\n <p>\n Laboratory</p>\n <p>\n Phone and internet access</p>\n </td>\n <td>\n <p>\n PI has over 10 years experience conducting clinical trials phase 1 to 4,and has experience in the similar sickle cell therapy trials, pharmacokinetic and pharmacogenomic studies.</p>\n </td>\n </tr>\n <tr>\n <td>\n KEMRI CRDR Research clinic at Chandaria Health Center</td>\n <td>\n <p>\n PI - Dr Videlis Nduba (MBCHB, MPH, PHD)</p>\n <p>\n Sub - I/SCC- Dr Grace Kiringa (MBCHB, Msc Clinical Trials)</p>\n <p>\n Pharmacist - Dr Tony Sang (BPharm)</p>\n <p>\n Lab Technician - Eric Njuki</p>\n </td>\n <td>\n <p>\n Consultation rooms</p>\n <p>\n Emergency Trolley</p>\n <p>\n Pharmacy</p>\n <p>\n Laboratory</p>\n <p>\n Phone and internet access</p>\n </td>\n <td>\n <p>\n PI has over 10 years experience conducting clinical trails phase 1 to 4. PI and site staff have experiece conducting sickle cell disease related trials including PK, PD and pharmacogenomic trials.</p>\n </td>\n </tr>\n <tr>\n <td>\n KEMRI Kondele Children's Hospital Center for Research</td>\n <td>\n <p>\n PI - Dr Bernhards Ogutu (MMed Paeds)</p>\n <p>\n Sub - I - Dr Godfrey Alan Otieno (MMed Paeds)</p>\n <p>\n SCC - Ishamel Sports</p>\n <p>\n  </p>\n </td>\n <td>\n <p>\n Consultation Rooms</p>\n <p>\n Hospitalization facilities</p>\n <p>\n Emergency Trolley, HDU</p>\n <p>\n Pharmacy</p>\n <p>\n Laboratory</p>\n <p>\n Phone and Internet access</p>\n </td>\n <td>\n <p>\n PI has over 10 years conducting clinical trials, phase 1 to 4 trials. PI , Sub-I and staff have previously conducted similar phase 3 Randomized Clinical Trials  in the sickle cell disease therapy area.</p>\n </td>\n </tr>\n <tr>\n <td>\n KEMRI Siaya Referral Hospital</td>\n <td>\n <p>\n PI - Dr Videlis Nduba (MBCHB. MPH, PHD)</p>\n <p>\n Sub - I - Dr Grace Kiringa(MBCHB, MSC. Clinical Trials)</p>\n <p>\n Pharmacist - Dr Tony Sang (Bpharm)</p>\n <p>\n SCC/Study Nurse - Elizabeth Akinyi</p>\n <p>\n Lab Technician  - Evans Ongesa</p>\n </td>\n <td>\n <p>\n Consultation rooms</p>\n <p>\n Hospitalization facilities</p>\n <p>\n Emergency Trolley</p>\n <p>\n Pharmacy</p>\n <p>\n Laboratory</p>\n <p>\n Phone and internet access</p>\n <p>\n  </p>\n </td>\n <td>\n <p>\n PI has over 10 years experience conducting Randomized clinical trials. PI and site staff have previously conducted similar phase 3 trials in the sickle cell therapy area. Site has experience in PK, PD and pharmacogenomic trials.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The trial will be conducted in the USA - the host country of the sponsor. There are 42 planned sites in United States.</p>\n
      • other_details_regulatory_notapproved<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 500px;\">\n <tbody>\n <tr>\n <td>\n COUNTRY and RA</td>\n <td>\n DATE OF SUBMISSION</td>\n </tr>\n <tr>\n <td>\n Egypt, Egyptian MOH central directorate of research and health development</td>\n <td>\n 23 Feb 2017</td>\n </tr>\n <tr>\n <td>\n Italy, Agenzia Italiano del Farmaco</td>\n <td>\n 27 Feb 2017</td>\n </tr>\n <tr>\n <td>\n Jamaica</td>\n <td>\n 01 Dec 2016</td>\n </tr>\n <tr>\n <td>\n Netherlands CCMO</td>\n <td>\n 14 Mar 2017</td>\n </tr>\n <tr>\n <td>\n Turkey, Turkish Medicine and Medical Device Agency</td>\n <td>\n 30 Dec 2016</td>\n </tr>\n </tbody>\n</table>\n<p>\n *Lebanon and Oman - Only EC submission only.</p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 500px;\">\n <tbody>\n <tr>\n <td>\n COUNTRY</td>\n <td>\n DATE OF APPROVAL</td>\n </tr>\n <tr>\n <td>\n UK, Medicines and Health Products Regulatory Authority</td>\n <td>\n 03 Feb 2017</td>\n </tr>\n <tr>\n <td>\n Canada, Health Canada</td>\n <td>\n 20 Jan 2017</td>\n </tr>\n <tr>\n <td>\n USA, Food and Drug Authority</td>\n <td>\n <p>\n Investigational New Drug submitted, Key elements of protocol - No Objection. FDA does not provide approval for ammendments.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration2 years (First site was opened in 29 Nov 2016. Study end is planned for Dec 2018)
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states15
      • number_of_sites5
      • multi_country_listCanada, Egypt, France, Ghana, Italy, Kenya, Nigeria, Jamaica, Lebanon, Netherlands, Oman, Qatar, Turkey, UK, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteminimum 2 maximum 30
      • total_participants_worldwide400
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJessie
      • investigator1_middle_nameNyokabi
      • investigator1_family_nameGithanga
      • investigator1_qualificationMBCHB, MMED (Path), FCPath
      • investigator1_professional_addressGertrude\'s Children\'s Hospital, Muthaiga Road, Off Thika Super Highway P.O Box 42325 - 00100, Nairobi, Kenya
      • investigator1_telephone+254721245721
      • investigator1_emailjgithanga3@gmail.com
      • organisations_transferred_Yes
      • number_participants100
      • notification<p>\n 1. Trial participants are adolescents from 12 - 17 years and adults 18 - 65 years.</p>\n<p>\n 2. The DSMB charter and Schedule of meetings is still under review. The draft document is attached.</p>\n<p>\n 3. The sites Budget is still not finalized. The breakdown of budget items is attached.</p>\n<p>\n 4. The scope of the study is the same at all sites. Same protocol through all sites globally.</p>\n
      • approval_date14-07-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-06-2021
      • 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)
      • modified2025-04-30 17:49:50
      • created2017-03-03 13:04:10
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id378
        • application_id598
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMBCHB, MPH (epi), PHD (epi)
        • professional_addressKEMRI CRDR, KNH Complex P.O Box 47855, Nairobi, Kenya
        • telephone+254724522474
        • emailvnduba@gmail.com
        • created2017-03-03 13:17:32
        • modified2021-06-28 11:42:10
      • 1(array)
        • id379
        • application_id598
        • given_nameJessie
        • middle_nameNyokabi
        • family_nameGithanga
        • qualificationMBCHB, MMED (Path), FCPath
        • professional_addressGertrude\'s Children\'s Hospital, Muthaiga Rd, Off Thika super-highway, P.O BOX 42325 - 00100, Nairobi, Kenya
        • telephone+254721245721
        • emailjgithanga3@gmail.com
        • created2017-03-03 13:23:11
        • modified2021-06-28 11:42:10
    • SiteDetail(array)
      • 0(array)
        • id475
        • application_id598
        • county_id47
        • site_nameGertrude\'s Children\'s Hospital
        • physical_addressAlong Muthaiga Road, Off Thika superhighway
        • contact_detailsP.O Box 42325 - 00100, Nairobi, Kenya
        • contact_personProf. Jessie Nyokabi Githanga
        • site_capacity(null)
        • misc(null)
        • created2017-03-03 13:17:32
        • modified2021-06-28 11:42:10
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id476
        • application_id598
        • county_id47
        • site_nameStrathmore University Medical Center
        • physical_addressMadaraka Estate, Ole Sangale Road, off Langata road
        • contact_detailsP.O. Box 59857 - 00200 Nairobi, Kenya
        • contact_personDr Benhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2017-03-09 10:39:23
        • modified2021-06-28 11:42:10
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id477
        • application_id598
        • county_id47
        • site_nameKEMRI CRDR Clinical Research clinic at Chandaria Health Center
        • physical_addressThogoto Mutarakwa Road - Near Dagoretti Market
        • contact_detailsP.O. Box 43678 - 00200, Nairobi, Kenya
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2017-03-09 10:39:23
        • modified2021-06-28 11:42:10
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id478
        • application_id598
        • county_id42
        • site_nameKEMRI Kondele Childrens Hospital Center for Clinical Research
        • physical_addressWithin Jaramogi Oginga Odinga Teaching and Referral Hospital, Along Kisumu - Kakamega Highway
        • contact_detailsP.O. Box 54 - 40100 Kisumu, Kenya
        • contact_personDr Benhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2017-03-09 10:39:23
        • modified2021-06-28 11:42:10
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 4(array)
        • id479
        • application_id598
        • county_id41
        • site_nameKEMRI Clinical Research Center at Siaya County Referral Hospital
        • physical_addressKEMRI/CDC Research Building at Siaya County Referral Hospital, Siaya
        • contact_detailsP.O. Box 144 - Siaya, Kenya
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2017-03-09 10:39:23
        • modified2021-06-28 11:42:10
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id304
        • application_id598
        • sponsorGlobal Blood Therapeutics, inc.
        • sponsor_typeResearch Institution
        • contact_personAllison Intondi
        • address400 East Jamie Court, Suite 101 South San Francisco, CA 94080, USA
        • telephone_number+1650 351 4720
        • fax_number+1650 751 7716
        • cell_numberNot applicable
        • email_addressaintondi@globalbloodtx.com
        • created2017-03-03 13:17:32
        • modified2021-06-28 11:42:10
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • approved2
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 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

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php