Phase 2 Expanded Safety Study of Tenofovir Gel in Pregnancy
Phase 2 Expanded Safety Study of Tenofovir Gel in Pregnancy
Preliminary research has shown that a vaginal gel containing the antiretroviral (ARV) drug tenofovir may reduce the risk of HIV infection in women when used near the time of sexual intercourse. This study will evaluate the safety of 1% tenofovir gel in HIV-uninfected pregnant women and their newborns when the gel is used once a day for a period of 28 days at a designated time during pregnancy.
Pregnant women often maintain sexual activity, and research has shown that they may have a greater risk of acquiring HIV infection during pregnancy. Preliminary research has suggested that tenofovir 1% gel, a vaginal microbicide, may reduce the risk of HIV infection for women when it is applied at the time of sexual intercourse. However, safety data on the use of tenofovir 1% gel during pregnancy are limited. This study will enroll pregnant women who will use tenofovir 1% gel on a daily basis for 28 consecutive days during their pregnancy, which is a longer period of use than has been studied previously. The purpose of this study is to evaluate the safety of 1% tenofovir gel in HIV-uninfected pregnant women when used during the late first trimester and second trimester of pregnancy.
Participants will be healthy, HIV-uninfected pregnant women and will be randomly assigned to use either 1% tenofovir gel or placebo gel once a day for 28 days or until delivery, whichever comes first. Participants will be further divided into four groups of varying gestational age ranges. These groups will be filled sequentially, starting with the later gestational ages (closer to the time of delivery) group first. Once the safety for this group is confirmed, groups of participants with earlier gestational ages will be enrolled.
Length of participation in this study will vary depending on gestational age at the time of enrollment, but each participant will have visits at study entry; Days 7, 14, and 28; 2 weeks after the last dose of the assigned gel; and once every 4 weeks until delivery. Participants who have used the gel within 24 hours of arriving at the hospital for delivery also will have a delivery visit. At most visits, participants will give a medical history; undergo blood and urine collection; and have a physical exam, including obstetric (OB) abdominal and pelvic exams. Participants also will report adverse events and complete an adherence assessment. If a participant has a delivery visit, blood will be collected from the umbilical cord and delivery and infant information will be collected. All participants will attend a follow-up study visit 30 days after delivery.
Inclusion Criteria:
Age 18 through 45 years (inclusive) at screening, verified per site standard operating procedures (SOPs)
At enrollment, singleton, viable pregnancy of gestational age within the limits for current group for enrollment
Per participant report, sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening
Able and willing to provide the following:
HIV-uninfected based on testing performed by study staff at screening and enrollment (per algorithm in protocol)
Per the clinical judgment of the Investigator of Record (IoR)/designee at enrollment, pelvic exam (including cervical exam) normal for estimated gestational age and parity
Per the clinical judgment of the IoR/designee at enrollment, ultrasound results are complete, consistent with normal singleton intrauterine pregnancy, and provide an assessment of gestational age. More information on this criterion can be found in the protocol.
Per participant mother report, willingness by the participant mother to receive information regarding and consider participation in MTN-016, a pregnancy registry study that collects additional information on pregnancy safety and the growth and development of babies up to 1 year of age
At screening and enrollment, agrees not to participate in other research studies involving drugs, vaccines, medical devices, or vaginal products for the duration of study participation
Exclusion Criteria:
Participant mother reported any of the following:
By participant mother report, noted on antenatal record, or clinical evidence at the time of enrollment of any of the following in the current pregnancy:
By participant mother report, or noted on review of medical record, any of the following in a previous pregnancy:
By participant mother report at screening or enrollment:
Currently breastfeeding
As determined by the IoR/designee, any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease, including active tuberculosis, or medication use that would make study participation unsafe. More information on this criterion can be found in the protocol.
At enrollment, clinically apparent Grade 2 or higher pelvic exam finding (observed by study staff). More information on this criterion can be found in the protocol.
Has any of the following laboratory abnormalities during the screening period:
Grade 2 or higher Pap result (e.g., high-grade squamous intraepithelial lesion). More information on this criterion can be found in the protocol.
Diagnosed with a sexually transmitted infection or reproductive tract infection requiring treatment, per current Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO) guidelines, as applicable. More information on this criterion can be found in the protocol.
Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives