The COMBAT HBV Feasibility Trial

NCT05705427 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 22-1492
• Study Type: interventional
• Target: 317
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blind, randomized placebo-controlled trial (RCT) of a prophylaxis-for-all approach to prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) in the Democratic Republic of Congo (DRC). HBV-infected pregnant women will be randomized to either receive tenofovir or placebo beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Women will be followed every 4-6 weeks throughout the prenatal and postpartum period to evaluate for side effects related to the medication. Infants will receive a birth-dose of HBV vaccine, ideally within 24 hours. Participants will be followed longitudinally through 6 months' postpartum.

Conditions

Hepatitis B; Vertical Transmission of Infectious Disease

Keywords

Prevention of mother-to-child transmission; Hepatitis B birth-dose vaccine; Tenofovir disoproxil fumarate

Outcome Measures

Primary Outcomes (10)

• Safety (Pregnant Women): Number of Pregnant Women With Adverse Effects Related to Study Medications

  Safety of TDF prophylaxis in pregnant women, defined as a composite of adverse events (# mild adverse events \[AEs\], # moderate-to-severe AEs), presence of side effects and alanine aminotransferase elevations ≥ 5x upper limit of normal

  Up to study close-out visit, or up to 12 months

• Safety (Infants): Number of Infants with Adverse Effects Related to Study Medications

  Safety of maternal TDF for infants, defined as a composite of: Birth weight (grams), mid-upper arm circumference (centimeters), gestational age at delivery (weeks and days), delivery mode (vaginal vs C-section), APGAR scores (0-10), # of adverse events

  At delivery

• Feasibility (Recruitment): Number of Eligible Participants Who Were Enrolled in the Study

  Recruitment is indicative of the number of pregnant women who are screened versus those actually enrolled in the study.

  Up to study close-out visit, or up to 12 months

• Feasibility (Refusal): Number of Eligible Participants Who Refused to Enroll in the Study

  Refusal will be defined as the number of individuals who refuse enrollment upon initial recruitment.

  Up to study close-out visit, or up to 12 months

• Feasibility (Withdrawal): Number of Enrolled Participants Who Withdraw from the Study

  Withdrawal is indicative of the number of enrolled participants who choose not to continue study activities after having been enrolled.

  Up to study close-out visit, or up to 12 months

• Feasibility (Retention): Number of Enrolled Participants Who Remain in the Study Through 6 Months Postpartum

  Retention is defined as the number of participants who remain in the study through the 6-month postpartum visit.

  Up to study close-out visit, or up to 12 months

• Feasibility (Maintenance): Proportion of Study Visits Completed Per Participant

  Adherence to study visits and procedures, defined as proportion of the actual number of visits attended divided by the expected study visits (8) and multiplied by 100.

  Up to study close-out visit (12 months)

• Acceptability (Lab Testing): Number of Mothers With Lab Testing Acceptability Scores >80%

  Number of mothers who report the process of undergoing lab draws as "acceptable" in the exit survey. Range 0-100%, with 0% being unacceptable and 100% being acceptable.

  Upon study close-out visit, or up to 12 months

• Acceptability (Medication): Number of Mothers With Medication Acceptability Scores >80%

  Number of mothers who report the process of taking the study medication as "acceptable" in the exit survey. Range 0-100%, with 0% being unacceptable and 100% being acceptable.

  Upon study close-out visit, or up to 12 months

• Preliminary Effectiveness: Number of Infants With HBV Positivity by Rapid Diagnostic Testing at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV

  Mother-to-child transmission of HBV is defined as HBsAg positivity in the infant at 6 months of life.

  Measured at 6 months after birth

Secondary Outcomes (2)

• Sensitivity of the Hepatitis B Core-Related Antigen Test

  Measured at Enrollment

• Specificity of the Hepatitis B Core-Related Antigen Test

  Measured at Enrollment

Study Arms (2)

Tenofovir disoproxil fumarate (TDF) arm

EXPERIMENTAL

140 pregnant women in the experimental arm will receive tenofovir disoproxil fumarate (TDF) 300 milligrams (mg) daily, beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Infants born to these women will be included in this arm and will receive a birth-dose of hepatitis B vaccine.

Drug: Tenofovir Disoproxil Fumarate 300 MG; Biological: Hepatitis B monovalent vaccine

Placebo arm

PLACEBO COMPARATOR

140 pregnant women in the placebo arm will receive a placebo pill daily, beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Infants born to these women will be included in this arm and will receive a birth-dose of hepatitis B vaccine.

Biological: Hepatitis B monovalent vaccine; Drug: Placebo

Interventions

Placebo DRUG

Pregnant women in the placebo arm will receive a placebo pill daily beginning in the 3rd trimester of pregnancy and continuing through 1 month postpartum.

Placebo arm

Tenofovir Disoproxil Fumarate 300 MG DRUG

Pregnant women in the experimental arm will receive TDF daily beginning in the 3rd trimester of pregnancy and continuing through 1 month postpartum.

Also known as: Viread

Tenofovir disoproxil fumarate (TDF) arm

Hepatitis B monovalent vaccine BIOLOGICAL

All infants born to women in the study will receive a birth-dose hepatitis B vaccine.

Also known as: Hepatitis B birth-dose vaccine, Engerix-B

Placebo arm; Tenofovir disoproxil fumarate (TDF) arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant women ≥18 years of age who present for routine prenatal care between 28-32 weeks' gestation and who test HBV-positive by point-of-care hepatitis B surface antigen test. Women must intend to seek maternity and postpartum care exclusively at one of the Kinshasa-based study maternity centers.
• Infants born to enrolled women will be included in the study

You may not qualify if:

• Individuals with abnormal creatinine by point-of-care testing
• Any woman who plans to move outside of Kinshasa Province during the study period.
• Any HIV-positive individual, determined by routine point-of-care screening at antenatal care visits

Sponsors & Collaborators

• Doris Duke Charitable Foundation: collaborator
• Université Protestant au Congo: collaborator
• Abbott: collaborator
• Albert Einstein College of Medicine: collaborator
• University of North Carolina, Chapel Hill: lead

Study Sites (1)

Université Protestant au Congo

Kinshasa, Democratic Republic of the Congo

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

Tenofovir; Engerix-B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Peyton Thompson, MD, MSCR

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The trial will be double-blinded, with study staff and participants blinded to allocation to the TDF vs placebo arm. Blinding to medication type will be achieved via use of over-encapsulation of TDF and placebo pills. Laboratory technicians who perform point-of-care hepatitis B core related antigen testing, HBV viral load testing and hepatitis B e antigen testing will be blinded to study arm.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pregnant women will be randomized at the time of enrollment (at 28-32 weeks' gestation) in a 1:1 ratio to receive tenofovir disoproxil fumarate (TDF) vs placebo, with an expected 140 women in the TDF arm and 140 in the placebo arm. A permuted block randomization technique will be employed to ensure equal distribution between the two arms at the two maternity centers. A biostatistician from the University of North Carolina (UNC) will design the randomization scheme, which will utilize the randomization-and-concealment feature within the REDCap database; the biostatistician will not be directly involved in study enrollment activities. REDCap personnel at UNC will ensure proper design and use of the randomization-and-concealment feature, and study personnel will receive training on the randomization process prior to study roll-out.

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: January 30, 2023
• Study Start: August 17, 2023
• Primary Completion: November 25, 2025
• Study Completion: November 25, 2025
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be available from 9 to 36 months after publication.
• Access Criteria: Interested individuals can request de-identified data with approval from an independent review committee, which will be shared upon execution of a Data Use/Sharing Agreement with UNC-CH.

Locations

DE (1)