Safety and Tolerability of 1 Month Daily (1HP) and 3 Months Weekly (3HP) Isoniazid and Rifapentine With Pharmacokinetics of Dolutegravir (DTG) in Pregnant People With HIV

NCT ID: NCT05122026

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-17
• Study Completion Date: 2025-12-31

Brief Summary

Open-label, two-arm, randomized multicenter study to investigate the safety, tolerability, and pharmacokinetics (PK), and potential interactions between dolutegravir (DTG) and rifapentine (RPT) during pregnancy in people with HIV when RPT is given with isoniazid (INH) daily for 4 weeks (1HP) or weekly for 3 months (3HP) as part of tuberculosis (TB) preventive therapy (TPT). Adults (age ≥18) who are pregnant with a singleton pregnancy (confirmed by ultrasound) at a gestational age of 20-34 weeks and virally suppressed on an existing DTG-based plus two nucleoside reverse transcriptase inhibitors (NRTI) antiretroviral (ART) regimen for at least four weeks may participate.

Detailed Description

Enrolled participants will be randomized 1:1 to Arms 1 and 2.

Arm 1: 1HP (n=126):

Participants will start twice-daily DTG on Day 0, and will receive once-daily HP for 28 total doses, starting on Day 1. HIV viral load (VL) will be measured at baseline (screening), week 3 (Day 17), at delivery, and post-partum week 12. Safety labs: complete blood count (CBC), urea and electrolytes (U&E), creatinine, prothrombin time and international normalized ratio (PT/INR), and liver function tests (LFT) will be obtained at screening for everyone and at follow-up visits, if clinically indicated; CBCs and LFTs will be checked at delivery in all participants.

The first 25 participants enrolled to Arm 1 who consent to be in a PK substudy will participate in sparse PK blood collections for DTG. Sparse PK sampling for DTG will be performed on the morning of Day 1, before starting 1HP and before the morning dose of DTG. Additional sparse PK sampling for DTG will be performed prior to DTG dosing on Day 17 (to track with 72 hours after the 3rd dose of HP in Arm 2).

A plasma specimen for RPT PK will also be collected on Day 17.

Arm 2: 3HP (n=126):

Participants will start twice-daily DTG on Day 0, and will receive once-weekly HP for 12 total doses starting on Day 1. HIV VL will be measured at baseline (screening), week 3 (Day 17), at delivery, and at post-partum week 12. Safety labs: CBC, U&E, creatinine, PT/INR, and LFTs will be obtained at screening for everyone and at follow-up visits, if clinically indicated; CBCs and LFTs will be drawn at delivery.

The first 25 participants enrolled to Arm 2 who consent to be in a PK substudy will participate in sparse PK blood collections for DTG. Sparse PK sampling for DTG will be performed on the morning of Day 1, before starting 3HP, and before the morning dose of DTG. Additional sparse PK sampling for DTG will be performed on Day 17 prior to DTG dosing (72 hours after the 3rd dose of HP) and on Day 52 prior to DTG dosing (72 hours after the 8th dose of HP).

There will not be plasma collection on Day 17 for RPT PK in Arm 2, because specimen collection would be 72 hours after the weekly HP dose and a RPT level will likely not be detectable.

Interim analysis will occur when 25 participants each from Arms 1 and 2 have completed the Week 3 (Day 17) sparse PK visit. Ongoing enrolment will not be paused during the interim analysis, which will assess DTG PK, safety, and VL data.

Enrollment will be paused if accrual to each arm reaches 101 participants before the interim analysis has been completed. Once results are available, then enrollment will restart with dosing (daily vs. BID) based on the DTG PK results.

Conditions

HIV Seropositivity; Pregnancy; Tuberculosis Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Arm 1: One month of daily isoniazid and rifapentine (4 weeks)

• DTG 50 mg orally BID

• DTG 50 mg + 2 NRTI each morning (non-study)
• 2nd dose: DTG 50 mg each evening (during 1HP)
• 1HP: INH 300 mg + RPT 600 mg each morning for 4 weeks

Group Type: EXPERIMENTAL

Rifapentine

Intervention Type: DRUG

As included in arm/group description

Isoniazid

Intervention Type: DRUG

As included in arm/group description

Arm 2: Three months of once-weekly isoniazid and rifapentine (12 weeks)

• DTG 50 mg orally BID

• DTG 50 mg + 2 NRTI each morning (non-study)
• 2nd dose: DTG 50 mg each evening (during 3HP)
• 3HP: INH 900 mg + RPT 900 mg each week for 12 weeks

Group Type: EXPERIMENTAL

Rifapentine

Intervention Type: DRUG

As included in arm/group description

Isoniazid

Intervention Type: DRUG

As included in arm/group description

Interventions

Rifapentine

As included in arm/group description

Intervention Type: DRUG

Isoniazid

As included in arm/group description

Intervention Type: DRUG

Other Intervention Names

Priftin; Winthrop Isoniazid

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years

2. Weight > 50 kg

3. Documented HIV infection

4. At least 4 weeks of ART and virally suppressed on dolutegravir plus two NRTIs

5. Undetectable HIV-1 viral load

6. Pregnancy at 20-34 weeks as confirmed by ultrasound

7. Singleton pregnancy

Exclusion Criteria

1. Confirmed or suspected TB disease

2. Likely to move from the study area during the study period

3. Known exposure to pulmonary TB cases with known or suspected resistance to isoniazid or rifampicin in the source case

4. TB treatment within the past year

5. TB preventive therapy within the last year

6. Sensitivity or intolerance to isoniazid or rifamycins

7. On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens

8. Suspected acute hepatitis or known chronic liver disease; HBsAg positivity; severe hepatic impairment

9. Alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN)

10. Total bilirubin ≥ 2.5 times the ULN

11. Absolute neutrophil count (ANC) < 750 cells/mm3

12. Creatinine clearance < 50 ml/min

13. Self-reported alcohol use exceeding 21 units per week

14. Karnofsky status < 80

15. On prohibited medications e.g. dofetilide

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: collaborator

The Aurum Institute NPC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr Vaneshree Govender

Role: PRINCIPAL_INVESTIGATOR

Aurum Institute

Locations

FAMily Centre for Research with Ubuntu (FAMCRU)

Cape Town, Cape Town, South Africa

The Aurum Institute: Tembisa Clinical Research Centre

Tembisa, Gauteng, South Africa

Peri Natal HIV Research Unit - Klerksdorp Tshepong Hospital

Klerksdorp, North West, South Africa

Countries

South Africa

Other Identifiers

3HP-MOMS-AUR1-6-351

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00299011

Identifier Type: -

Identifier Source: org_study_id