- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03965923
Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy
Phase 3b, Randomized, Open Label Safety Trial of Dapivirine Vaginal Ring and Oral TRUVADA® Use in Pregnancy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The purpose of this study is to evaluate the maternal and infant safety of the dapivirine (DPV) vaginal ring (VR) and daily oral Truvada in HIV-uninfected pregnant women and their infants.
Participants will be assigned to one of three cohorts based on gestational age:
- Cohort 1: 36 0/7 weeks - 37 6/7 weeks
- Cohort 2: 30 0/7 weeks - 35 6/7 weeks
- Cohort 3: 12 0/7 weeks - 29 6/7 weeks
Within each cohort, participants will be randomized to receive either DPV VR or oral Truvada. Participants randomized to the DPV VR will use the VR continuously for approximately one month, replacing the VR each month. Participants taking the Truvada tablet will take one tablet orally per day. Participants will use their assigned study product until their pregnancy outcome, but no later than 41 6/7 weeks of gestation.
Participants will attend several study visits throughout the study and study staff will also contact participants by phone at different timepoints throughout the study.
The total duration of study participation will vary depending on gestational age at time of enrollment and length of pregnancy prior to pregnancy outcome and will range from approximately 12 weeks or less for Cohort 1 to approximately 36 weeks or less for Cohort 3. Infants born to study participants will be followed for approximately 52 weeks.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Blantyre, Malawi
- Blantyre CRS (Johns Hopkins Research Project/College of Medicine)
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Gauteng
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Johannesburg, Gauteng, South Africa, 2001
- Wits RHI Shandukani Research Centre CRS
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Kampala, Uganda
- MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
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Mashonaland East
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Chitungwiza, Mashonaland East, Zimbabwe
- Zengeza CRS
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18 through 40 years (inclusive) at Enrollment, verified per site standard operating procedures (SOPs).
At Enrollment, evidence of a viable, intrauterine, singleton pregnancy with sonographic confirmation, including for gestational age assessment.
- Note: If adequate (per judgment of Investigator of Record [IoR]/designee) sonographic results are not available from medical records at Screening, an ultrasound must be performed and results be available for review at Enrollment for all Cohorts. The ultrasound should be performed no later than the 36th week of gestation for Cohort 1 or the 28th week of gestation for Cohort 2.
- At Enrollment, pregnancy within gestational age limits of the currently enrolling cohort (per the study protocol).
- HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithm in the study protocol).
- At Screening and Enrollment, intending to continue her pregnancy until delivery.
At Screening and Enrollment, intending to deliver at a health center or hospital where adequate records may be obtained, as defined in site SOPs.
- Note: Plans to deliver at a health center or hospital where adequate records may be obtained is inclusionary due to logistical challenges related to collection of vaginal rings (VRs), specimens and delivery outcome data outside of those settings.
- At Screening and Enrollment, willing to be randomized at time of enrollment to either of the two study arms, and to continue study product use until delivery.
- Able and willing to comply with all study requirements and complete all study procedures.
Able and willing to provide the following:
- Informed consent for her and her infant to be screened for and to enroll in MTN-042, as defined in site SOPs.
- Adequate locator information, as defined in site SOPs.
- Adequate documentation of registration for antenatal care, as defined in site SOPs.
- Permission to contact participant's antenatal and postpartum care provider(s) and to obtain copies of antenatal and postpartum care records.
- At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation, unless approved by the Protocol Safety Review Team (PSRT).
Exclusion Criteria:
Per participant report at Screening and/or Enrollment, intends to do any of the following during the study participation period:
- Use oral pre-exposure prophylaxis (PrEP) outside the context of study participation.
- Relocate away from the study site.
- Travel away from the study site for a time period that would interfere with study participation.
- At Screening or Enrollment, has a positive HIV test.
At Screening or Enrollment, diagnosed with urinary tract infection (UTI), cervicitis, sexually transmitted infection (STI) or reproductive tract infection (RTI) requiring treatment per World Health Organization (WHO) guidelines.
- Note: Detection of bacterial vaginosis (BV) or candida in the absence of symptoms is not exclusionary. Otherwise eligible participants diagnosed during screening with a UTI, cervicitis, or STI/RTI requiring treatment per WHO guidelines are offered treatment consistent with WHO recommendations. If treatment is completed and symptoms have resolved within 35 days of obtaining informed consent for screening, the participant may be enrolled.
At Enrollment, has a clinically apparent Grade 2 or higher pelvic exam finding.*
- 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 Investigator of Record (IoR)/designee is considered expected bleeding and is not exclusionary.
Participant report, clinical evidence and/or antenatal/medical care record of any of the following:
- Currently breastfeeding at Enrollment.
- Known adverse reaction to any of the study products (ever).
- Known adverse reaction to latex and polyurethane (ever).
- Symptoms suggestive of acute HIV infection at Screening or Enrollment.
- Non-therapeutic injection drug use in the 12 months prior to Enrollment.
- Use of HIV post-exposure prophylaxis (PEP) and/or PrEP during the current pregnancy.
- Participation in any other research study involving drugs, medical devices, vaginal products, or vaccines during the current pregnancy.
At Screening or Enrollment, known to have any of the following during the current pregnancy:
- Multiple gestation
- Placenta previa
- Cervical cerclage
- Abnormal fetal anatomy (in the opinion of the IoR or designee)
- Intrauterine growth restriction
- Pre-existing or gestational diabetes
- Hypertensive disorder of pregnancy
- Severe malaria
- Treatment for preterm labor
- Abnormal quantity of amniotic fluid (oligohydramnios or polyhydramnios)
At Screening, known to have had any of the following in a previous pregnancy:
- Intrauterine growth restriction
- Gestational diabetes
- Hypertensive disorder of pregnancy
- Intrauterine fetal demise (estimated gestational age greater than or equal to 20 weeks)
- Delivery prior to 37 0/7 weeks
- At Enrollment, as determined by the IoR/designee, has any significant obstetrical complication (e.g., premature rupture of membranes, any abnormal placentation) or uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease that would make study participation unsafe.
At Screening, has any of the following laboratory abnormalities:
- Positive for hepatitis B surface antigen (HBsAg).
- Aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than or equal to Grade 1.**
- Hemoglobin greater than or equal to Grade 2.**
- Platelet count greater than or equal to Grade 1.**
- Creatinine greater than or equal to Grade 1.**
- Estimated creatinine clearance greater than or equal to Grade 2 (Cockcroft Gault formula).**
- Glycosuria greater than or equal to Grade 2.**
- Proteinuria greater than or equal to Grade 2.**
- Note: Otherwise eligible participants with an exclusionary test (other than HBsAg) may be re-tested during the screening process; re-testing procedure details can be found in the MTN-042 Study Specific Procedures (SSP) Manual. If improvement to a non-exclusionary grade or resolution is documented within 35 days of providing informed consent for screening, the participant may be enrolled.
- Has any condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
- *Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated November 2007) to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.
- **DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 2017.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Cohort 1: Dapivirine (DPV) Vaginal Ring (VR)
Participants in Cohort 1 (36 0/7 weeks - 37 6/7 weeks) will use one DPV VR continuously for approximately one month, replacing the DPV VR each month.
Participants will use the DPV VR until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
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Vaginal ring containing 25 mg of DPV
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EXPERIMENTAL: Cohort 1: Truvada Tablet
Participants in Cohort 1 (36 0/7 weeks - 37 6/7 weeks) will take one Truvada oral tablet daily.
Participants will take Truvada until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
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Tablet taken orally
Other Names:
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EXPERIMENTAL: Cohort 2: Dapivirine (DPV) Vaginal Ring (VR)
Participants in Cohort 2 (30 0/7 weeks - 35 6/7 weeks) will use one DPV VR continuously for approximately one month, replacing the DPV VR each month.
Participants will use the DPV VR until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
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Vaginal ring containing 25 mg of DPV
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EXPERIMENTAL: Cohort 2: Truvada Tablet
Participants in Cohort 2 (30 0/7 weeks - 35 6/7 weeks) will take one Truvada oral tablet daily.
Participants will take Truvada until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
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Tablet taken orally
Other Names:
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EXPERIMENTAL: Cohort 3: Dapivirine (DPV) Vaginal Ring (VR)
Participants in Cohort 3 (12 0/7 weeks - 29 6/7 weeks) will use one DPV VR continuously for approximately one month, replacing the DPV VR each month.
Participants will use the DPV VR until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
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Vaginal ring containing 25 mg of DPV
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EXPERIMENTAL: Cohort 3: Truvada Tablet
Participants in Cohort 3 (12 0/7 weeks - 29 6/7 weeks) will take one Truvada oral tablet daily.
Participants will take Truvada until their pregnancy outcome but no later than 41 6/7 weeks of gestation.
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Tablet taken orally
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Frequency of all serious maternal adverse events, including maternal deaths
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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As defined by the Manual for Expedited Reporting of Adverse Events to Division of AIDS (DAIDS) (Version 2.0, January 2010)
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of all Grade 3 or higher maternal adverse events (AEs)
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies [Dated November 2007])
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of all serious infant adverse events, including infant deaths and congenital anomalies
Time Frame: Measured through Week 52
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As defined by the Manual for Expedited Reporting of Adverse Events to DAIDS (Version 2.0, January 2010)
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Measured through Week 52
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Frequency of all Grade 3 or higher infant AEs
Time Frame: Measured through Week 52
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As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
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Measured through Week 52
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Frequency of full term live births (greater than or equal to 37 0/7 weeks)
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of premature live births (less than 37 0/7 weeks)
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of pregnancy loss (greater than or equal to 20 0/7 weeks)
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of pregnancy loss (less than 20 0/7 weeks)
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency of hypertensive disorders of pregnancy
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of chorioamnionitis
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of puerperal sepsis
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of endometritis
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of peripartum hemorrhage
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of postpartum hemorrhage
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of preterm premature rupture of membranes (PROM)
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Frequency of fever of unclear etiology
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Infant blood tenofovir diphosphate (TFV-DP) concentrations
Time Frame: Measured at the 2-week post pregnancy outcome (PPO) visit
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Based on laboratory evaluations
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Measured at the 2-week post pregnancy outcome (PPO) visit
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Infant blood emtricitabine triphosphate (FTC-TP) concentrations
Time Frame: measured at the 2-week post pregnancy outcome (PPO) visit
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Based on laboratory evaluations
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measured at the 2-week post pregnancy outcome (PPO) visit
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Infant plasma DPV concentrations
Time Frame: measured at the 2-week post pregnancy outcome (PPO) visit
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Based on laboratory evaluations
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measured at the 2-week post pregnancy outcome (PPO) visit
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Maternal blood TFV-DP concentrations
Time Frame: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
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Based on laboratory evaluations
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Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
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Maternal blood FTC-TP concentrations
Time Frame: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
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Based on laboratory evaluations
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Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
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Maternal plasma DPV concentrations
Time Frame: Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
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Based on laboratory evaluations
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Measured through participant's 2-week PPO visit, at approximately Week 8-32, depending on participant's cohort
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Frequency of study product use
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Based on participant report, as defined by missed doses for oral Truvada and VR removal/expulsions [voluntary and involuntary] and duration without VR in vagina
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Residual drug levels in returned VRs
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Based on laboratory evaluations
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Participant willingness to use study products during pregnancy (Y/N)
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Based on participant report
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Proportion of participants who find the study products to be at least as acceptable as other HIV prevention methods
Time Frame: Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Based on participant report
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Measured through participant's last study visit, at approximately Week 12 to 36, depending on participant's cohort
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Collaborators and Investigators
Investigators
- Study Chair: Katherine Bunge, MD, MPH, University of Pittsburgh
- Study Chair: Felix Mhlanga, MBChB, MMed, Zengeza Clinical Research Site
- Study Chair: Lee Fairlie, WITS RHI Shandukani Research Centre
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
- Emtricitabine
- Dapivirine
- Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Other Study ID Numbers
- MTN-042
- 38544 (REGISTRY: DAIDS-ES Registry Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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