Evaluating the Safety of Tenofovir Vaginal Gel in HIV-Uninfected Pregnant Women

NCT01490671 | Withdrawn Phase 2 DMC

• 2 other identifiers: MTN-01911839
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Maternal outcomes: Grade 2 or higher adverse events (AEs) in select categories

  Categories include: specific laboratory abnormalities, specific genital/pelvic signs/symptoms, and pregnancy complications

  Measured through participant's last study visit, which will occur 30 days after delivery

• Neonatal outcomes (first 30 days of life): All serious adverse events (SAEs)

  Measured through the 30 day follow-up visit

Secondary Outcomes (4)

• Pharmacokinetics of tenofovir in mothers

  Measured at Day 14 visit

• Self-reported product use captured through questionnaires

  Measured through participant's last study visit, which will occur 30 days after delivery

• Adherence to study gel as indicated by study drug levels in blood sample

  Measured through participant's last study visit, which will occur 30 days after delivery

• Adherence to study gel obtained by count of returned unused applicators

  Measured through participant's last study visit, which will occur 30 days after delivery

Study Arms (8)

Group 1a (tenofovir gel)

EXPERIMENTAL

Group 1a will include women with a gestational age range of 36 0/7 to 37 6/7 weeks; they will receive 1% tenofovir gel

Drug: 1% tenofovir gel

Group 1b (placebo gel)

PLACEBO COMPARATOR

Group 1b will include women with a gestational age range of 36 0/7 to 37 6/7 weeks; they will receive placebo gel.

Drug: Placebo gel

Group 2a (tenofovir gel)

EXPERIMENTAL

Group 2a will include women with a gestational age range of 28 0/7 to 32 6/7 weeks; they will receive 1% tenofovir gel.

Drug: 1% tenofovir gel

Group 2b (placebo gel)

PLACEBO COMPARATOR

Group 2b will include women with a gestational age range of 28 0/7 to 32 6/7 weeks; they will receive placebo gel.

Drug: Placebo gel

Group 3a (tenofovir gel)

EXPERIMENTAL

Group 3a will include women with a gestational age range of 20 0/7 to 24 6/7 weeks; they will receive 1% tenofovir gel.

Drug: 1% tenofovir gel

Group 3b (placebo gel)

PLACEBO COMPARATOR

Group 3b will include women with a gestational age range of 20 0/7 to 24 6/7 weeks; they will receive placebo gel.

Drug: Placebo gel

Group 4a (tenofovir gel)

EXPERIMENTAL

Group 4a will include women with a gestational age range of 12 0/7 to 16 6/7 weeks; they will receive 1% tenofovir gel.

Drug: 1% tenofovir gel

Group 4b (placebo gel)

PLACEBO COMPARATOR

Group 4b will include women with a gestational age range of 12 0/7 to 16 6/7 weeks; they will receive placebo gel.

Drug: Placebo gel

Interventions

1% tenofovir gel DRUG

One applicator of 1% tenofovir gel will be inserted by the participant into the vagina once each day for 28 days or until delivery, whichever comes first

Group 1a (tenofovir gel); Group 2a (tenofovir gel); Group 3a (tenofovir gel); Group 4a (tenofovir gel)

Placebo gel DRUG

One applicator of placebo gel will be inserted by the participant into the vagina once each day for 28 days or until delivery, whichever comes first

Group 1b (placebo gel); Group 2b (placebo gel); Group 3b (placebo gel); Group 4b (placebo gel)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Written informed consent to be screened for and take part in the study
• Adequate locator information, as defined in site SOPs
• Adequate documentation of entry to antenatal care, as defined in site SOPs
• Permission to contact and provision of adequate contact information for participant's antenatal care provider
• Permission to obtain copies of antenatal care records More information on this criterion can be found in the protocol.
• 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

You may not qualify if:

• Participant mother reported any of the following:
• Prior exposure to gel or oral formulation of tenofovir (ever)
• Known sensitivity to any component of the study products (ever)
• Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to enrollment
• Participation in any research study involving drugs, medical devices, or vaginal products during the current pregnancy
• Non-therapeutic injection drug use in the 12 months prior to screening
• 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:
• 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
• Treatment for preterm labor

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Related Publications (2)

• Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D; CAPRISA 004 Trial Group. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168-74. doi: 10.1126/science.1193748. Epub 2010 Jul 19.

  PMID: 20643915 BACKGROUND

• Nurutdinova D, Onen NF, Hayes E, Mondy K, Overton ET. Adverse effects of tenofovir use in HIV-infected pregnant women and their infants. Ann Pharmacother. 2008 Nov;42(11):1581-5. doi: 10.1345/aph.1L083. Epub 2008 Oct 28.

  PMID: 18957630 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Richard H Beigi, MD, MSc

  University of Pittsburgh

  STUDY CHAIR

• Bonus Makanani, MBBS, FCOG (SA)

  Kamuzu University of Health Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2011
• First Posted: December 13, 2011
• Primary Completion: August 1, 2015
• Last Updated: November 1, 2021

Record last verified: 2021-10