IPM 014A protocol synopsis - International Partnership For ...

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IPM014A 24 February 2009Final Version 5.0 Page 9 of 76PROTOCOL SYNOPSISIPM014AA DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE I/II STUDY TOEVALUATE THE SAFETY AND ACCEPTABILITY OF DAPIVIRINE GEL 4759, 0.05% 2.5G, AVAGINAL MICROBICIDE, CONDUCTED USING DAILY MONITORED ADHERENCE INHEALTHY HIV-NEGATIVE WOMENBACKGROUND:OBJECTIVES:To date, candidate vaginal microbicides have been formulatedpredominantly as gels. Multiple safety and efficacy studies with variousmicrobicides are currently underway, most of which are designed todeliver the microbicide in gel form via a single-use vaginal applicator justprior to coitus. However, at the present time, there is no standardized andvalidated method to accurately ensure adherence of gel use. Furthermore,anecdotal evidence suggests that adherence of using gel before coitusmay be lower than expected and may be a critical factor in assessingmicrobicide efficacy in a Phase III study. Under certain situations wheretreatment non-adherence may be a public health concern, such as fortuberculosis and HIV infection, medication has been administered by amethod called Directly Observed Therapy (DOT) whereby a health careprovider, family member or member of the community directly observesthe administration of medication on a daily basis to ensure adherence andproper treatment. To reduce the influence of adherence as a factor in theinterpretation of efficacy results, IPM is considering using a DOT basedmethod for vaginal microbicide gel delivery in a future Phase III study. IPMhas denoted this DOT based method as Daily Monitored Adherence(DMA). IPM014A is a Phase I/II study designed: (1) to assess andcompare the safety of a once daily application of Dapivirine Gel 4759,0.05% 2.5g and a matching vehicle placebo gel; (2) to assess theacceptability of a once daily application of Dapivirine gel 4759, 0.05% 2.5gand a matching vehicle placebo gel; and (3) to assess the feasibility ofutilizing the DMA method for a large-scale phase III efficacy study.The primary objectives are:• To assess and compare the safety of a once daily application ofDapivirine Gel 4759, 0.05% 2.5g, a vaginal microbicide, to amatching vehicle placebo gel over a 6-week period in healthy,sexually active, HIV-negative women.The secondary objectives are:• To assess the acceptability of a once daily application of a vaginalmicrobicide over a 6-week period in healthy, sexually active, HIVnegativewomen.• To assess the feasibility of utilizing DMA in a Phase III vaginalmicrobicide gel study.• To evaluate adherence to daily use of vaginal gel and factorspredicting adherence.Restricted * Confidential – Limited Access*
IPM014A 24 February 2009Final Version 5.0 Page 10 of 76• To assess the effect of Dapivirine Gel 4759, 0.05% 2.5g on thevaginal flora and vaginal pH as compared with a matching vehicleplacebo gel.• To assess condom use and sexual behaviour of women using anintravaginal microbicide with DMA.ENDPOINTS:To address the primary objectives, the following will be assessed:• Gynaecological examinations, including pelvic/speculumexamination and colposcopy, and laboratory STI testing.• Safety laboratory tests.• Adverse event/serious adverse event reports.To address the secondary objectives, the following will be assessed:• Questionnaires concerning acceptability and adherence to dailyuse of vaginal gel.• Documentation of adherence to the DMA method including theApplicator Collection Checklist, focus groups and maleinterviews.• Quantitative measures of adherence to daily use of vaginal gelas assessed by reconciliation of returned applicators and coitallogs.• Vaginal flora and vaginal pH analysis.• Self-reported condom use and sexual behaviour.DESIGN:IPM014A is a double-blind, randomized, placebo-controlled Phase I/IIstudy conducted at up to 10 research centres in Kenya, Malawi, Rwanda,South Africa and Tanzania among approximately 320 healthy, sexuallyactive, HIV-negative women to assess the safety and acceptability ofDapivirine Gel 4759, 0.05% 2.5g, a vaginal microbicide. Upon enrolmentat each research centre, participants will be randomly assigned in a 1:1ratio to one of two study groups: those using dapivirine Gel 4759, 0.05%2.5g once daily for a period of 6 weeks, or those using the matchingvehicle placebo gel containing no dapivirine once daily for a period of 6weeks. Using the DMA method, designated study staff will monitoradherence by collecting used/unused applicators from both groups ofwomen on a daily basis Monday to Friday. On Saturday, Sunday andPublic Holidays participants may not have contact with study staff, and willthen return used/unused applicators on the following Monday, or in thecase of a public holiday, on the following working day. After the screeningperiod (up to 28 days), both groups will participate in the study for a periodof 10 weeks, including a follow-up visit 4 weeks post gel discontinuation.At each research centre, 12-20 women participating in the study may beasked to participate in focus groups to assess gel acceptability and thefeasibility of conducting a Phase III study utilizing the DMA method. Ateach research centre, 6-10 male partners of women participating in thestudy may be asked to participate in individual interviews to assess gelacceptability and the feasibility of conducting a Phase III study utilizing theDMA method. Assays may be performed on returned applicators toconfirm that intravaginal applicators have been used correctly.Restricted * Confidential – Limited Access*
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