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

NCT05122026 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: IRB002990113HP-MOMS-AUR1-6-351
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 3

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.

Conditions

HIV Seropositivity; Pregnancy; Tuberculosis Infection

Keywords

Dolutegravir; 3HP; Rifapentine; pharmacokinetic; TB preventive treatment

Outcome Measures

Primary Outcomes (5)

• Mortality

  Maternal all-cause mortality (both groups)

  from study entry at Week 0 through post partum Week 24, to be reported at end of trial

• Targeted serious adverse events (SAEs)

  Premature discontinuation for toxicity or intolerance, Grade 3 or higher maternal bleeding, peripheral neuropathy, elevated LFTs), targeted pregnancy outcomes (fetal demise, stillbirth, preterm delivery (PTD) \<32 weeks, birthweight (BW) \<1500g, neonatal death \<28 days of age), or permanent discontinuation due to toxicity (both groups)

  from study entry at Week 0 through post partum Week 12, to be reported at end of trial

• PK sampling of Dolutegravir - Cl/F parameter

  Oral clearance in the presence or absence of 1HP or 3HP (both groups)

  PK sampling at Week 1 (Day 1) and Week 3 (Day 17) for both groups, and at Week 8 (Day 52) for Group 2 (3HP arm), to be reported at end of trial

• PK sampling of Dolutegravir - AUC parameter

  Area under the plasma drug concentration-time curve (AUC) in the presence or absence of 1HP or 3HP (both groups)

  PK sampling at Week 1 (Day 1) and Week 3 (Day 17) for both groups, and at Week 8 (Day 52) for Group 2 (3HP arm), to be reported at end of trial

• PK sampling of Dolutegravir - Ctau parameter

  Trough concentration (Ctau) in the presence or absence of 1HP or 3HP (both groups)

  PK sampling at Week 1 (Day 1) and Week 3 (Day 17) for both groups, and at Week 8 (Day 52) for Group 2 (3HP arm), to be reported at end of trial

Secondary Outcomes (14)

• HIV-1 RNA viral load- maternal

  HIV viral load to be measured at Screening, Week 3, at Delivery, and post partum Week 12, to be reported at end of trial

• DTG Dose selection

  Dose selection will be determined at the interim analysis to be conducted when 25 participants from Arms 1 and 2 respectively have completed the Week 3 PK visit. Based upon these results, new enrollees will receive DTG either once or twice daily.

• PK sampling of RPT - AUC parameter

  PK sampling at Week 3 (Day 17 ) to be reported at end of trial

• PK sampling of RPT - Ctau parameter

  PK sampling at Week 3 (Day 17 ) to be reported at end of trial

• Adverse Events- maternal

  from study entry at Week 0 through post partum Week 12, to be reported at end of trial

Study Arms (2)

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

EXPERIMENTAL

* 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

Drug: Rifapentine; Drug: Isoniazid

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

EXPERIMENTAL

* 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

Drug: Rifapentine; Drug: Isoniazid

Interventions

Rifapentine DRUG

As included in arm/group description

Also known as: Priftin

Arm 1: One month of daily isoniazid and rifapentine (4 weeks); Arm 2: Three months of once-weekly isoniazid and rifapentine (12 weeks)

Isoniazid DRUG

As included in arm/group description

Also known as: Winthrop Isoniazid

Arm 1: One month of daily isoniazid and rifapentine (4 weeks); Arm 2: Three months of once-weekly isoniazid and rifapentine (12 weeks)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Weight \> 50 kg
• Documented HIV infection
• At least 4 weeks of ART and virally suppressed on dolutegravir plus two NRTIs
• Undetectable HIV-1 viral load
• Pregnancy at 20-34 weeks as confirmed by ultrasound
• Singleton pregnancy

You may not qualify if:

• Confirmed or suspected TB disease
• Likely to move from the study area during the study period
• Known exposure to pulmonary TB cases with known or suspected resistance to isoniazid or rifampicin in the source case
• TB treatment within the past year
• TB preventive therapy within the last year
• Sensitivity or intolerance to isoniazid or rifamycins
• On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens
• Suspected acute hepatitis or known chronic liver disease; HBsAg positivity; severe hepatic impairment
• Alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN)
• Total bilirubin ≥ 2.5 times the ULN
• Absolute neutrophil count (ANC) \< 750 cells/mm3
• Creatinine clearance \< 50 ml/min
• Self-reported alcohol use exceeding 21 units per week
• Karnofsky status \< 80
• On prohibited medications e.g. dofetilide

Sponsors & Collaborators

• The Aurum Institute NPC: lead
• Johns Hopkins University: collaborator
• University of Washington: collaborator
• Weill Medical College of Cornell University: collaborator

Study Sites (3)

FAMily Centre for Research with Ubuntu (FAMCRU)

Cape Town, Cape Town, 7505, South Africa

Location

The Aurum Institute: Tembisa Clinical Research Centre

Tembisa, Gauteng, 1632, South Africa

Location

Peri Natal HIV Research Unit - Klerksdorp Tshepong Hospital

Klerksdorp, North West, 2571, South Africa

Location

MeSH Terms

Conditions

HIV Seropositivity; Latent Tuberculosis

Interventions

rifapentine; Isoniazid

Condition Hierarchy (Ancestors)

HIV Infections; 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; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Latent Infection

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Dr Vaneshree Govender

  Aurum Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 1:1 to receive either 1HP or 3HP

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: November 16, 2021
• Study Start: January 17, 2024
• Primary Completion: October 24, 2025
• Study Completion: December 31, 2025
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (3)