Pharmacokinetics and Safety of Double-dose Dolutegravir When Used With Rifapentine for HIV-associated Tuberculosis

NCT05630872 | Completed Phase 2 FDA Drug

• 1 other identifier: A5406
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 4

Brief Summary

A5406 hypothesizes that dolutegravir (DTG) 50 mg taken twice daily will provide adequate exposures to maintain viral suppression when dosed with rifapentine (RPT) 1200 mg for HIV-associated TB.

Conditions

HIV-associated Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Model-simulated 5th percentile and corresponding 95% confidence interval of DTG minimum concentrations (Cmin) at 50 mg BID when co-administered with daily RPT 1200 mg plus HZM

  48 Weeks

Secondary Outcomes (8)

• DTG minimum concentration (Cmin)

  48 Weeks

• DTG minimum concentration (Cmax)

  48 Weeks

• DTG area under the concentration-time curve (AUC0-24)

  48 Weeks

• Number of participants who experience Grade 3 or higher AEs

  Weeks 6-17

• Number of participants who have a diagnosis of rifamycin hypersensitivity

  Weeks 6-17

Study Arms (1)

Adults with HIV and newly diagnosed DS-TB not currently on ART

EXPERIMENTAL

Participants will receive daily rifapentine-moxifloxacin plus isoniazid and pyrazinamide for 8 weeks followed by daily rifapentine-moxifloxacin plus isoniazid for 9 weeks (referred to as 2HPZM/2HPM) for anti-tuberculosis (anti-TB) therapy at study entry. DTG-based ART at 50 mg twice daily (BID) will be started after 6 weeks of TB therapy and will be continued for 2 weeks after completion of TB therapy. Two weeks after completion of TB therapy DTG will be reduced to standard dose 50 mg once daily (QD).

Drug: Dolutegravir (DTG) 50 mg orally BID (~12 hours apart) plus TDF/3TC; Drug: DTG 50 mg orally QD plus TDF/3TC; Drug: 2HPZM; Drug: 2HPM

Interventions

2HPZM DRUG

Daily rifapentine-moxifloxacin plus isoniazid and pyrazinamide regimen

Adults with HIV and newly diagnosed DS-TB not currently on ART

Dolutegravir (DTG) 50 mg orally BID (~12 hours apart) plus TDF/3TC DRUG

Dolutegravir (DTG) 50 mg orally BID (\~12 hours apart) plus TDF/3TC, from study week 6 until 2 weeks after completion of TB treatment: Morning dose DTG 50 mg QD plus TDF/3TC from study-supplied ARV regimen. Evening dose: DTG 50 mg orally QD from study-supplied source.

Adults with HIV and newly diagnosed DS-TB not currently on ART

DTG 50 mg orally QD plus TDF/3TC DRUG

DTG 50 mg orally QD plus TDF/3TC from two weeks after completion of TB treatment to end of study (week 48).

Adults with HIV and newly diagnosed DS-TB not currently on ART

2HPM DRUG

Daily rifapentine-moxifloxacin plus isoniazid regimen

Adults with HIV and newly diagnosed DS-TB not currently on ART

Eligibility Criteria

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

You may qualify if:

• Individuals ≥18 years of age at study entry.
• Weight ≥40 kg.
• Body mass index (BMI) \>18.5 kg/m2.
• Ability and willingness of participant or legal guardian/representative to provide informed consent.
• Documentation of HIV-1 status.
• CD4+ cell count ≥100 cells/mm3 obtained within 30 days prior to study entry at any network-approved non-US laboratory that is IQA certified.
• ART-naïve or not on ART for 12 consecutive weeks prior to TB diagnosis.
• Willingness and eligibility to start DTG-based ART at 6 weeks, with a window of ±1 week, after starting TB treatment, with no intention to change ART for the duration of the study.
• Documentation of pulmonary TB.
• Willingness to start 2HPZM/2HPM therapy for DS-TB.
• The following laboratory values obtained within 30 days prior to study entry:
• Absolute neutrophil count (ANC) \>750 cells/mm3
• Hemoglobin ≥7.4 g/dL
• Platelet count ≥50,000/mm3
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) \<2.5 X the upper limit of normal (ULN)

You may not qualify if:

• Breastfeeding, pregnant, or plans to become pregnant.
• Known allergy/sensitivity or any hypersensitivity to components of the study drugs, or their formulations.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Requirement for ongoing use of drugs that are known to have significant drug-drug interactions with DTG or RPT.
• Known history of acute intermittent porphyria.
• Previous treatment for active TB disease.
• More than 5 days of treatment directed against active TB for the current TB episode preceding study entry.
• At the time of study entry, documentation of an M. tuberculosis isolate from the current or previous treatment episode known to be resistant to RIF or INH.
• Known history of prolonged QT syndrome.
• Known cirrhosis, a history of decompensated liver disease (ascites, hepatic encephalopathy, or esophageal varices).
• Documentation of severe opportunistic infections, in the opinion of the site investigator, within 3 months of study entry.
• Documentation of severe extra-pulmonary TB (e.g., meningitis, osteomyelitis, disseminated TB) at the time of screening.
• Acute gout at the time of screening.

Sponsors & Collaborators

• ViiV Healthcare: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Mylan Inc.: collaborator

Study Sites (4)

University of Cape Town Lung Institute (UCTLI) CRS (Site # 31792)

Mowbray, Cape Town, Western Cape, 7700, South Africa

Location

Durban International CRS (Site # 11201)

Westridge, Durban RSA, 4091, South Africa

Location

South African Tuberculosis Vaccine Initiative (SATVI) CRS (Site # 31793)

Worcester, Western Province, 6850, South Africa

Location

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (Site # 31802)

Bangkok, 6850, Thailand

Location

MeSH Terms

Interventions

dolutegravir

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2022
• First Posted: November 30, 2022
• Study Start: February 13, 2024
• Primary Completion: May 7, 2025
• Study Completion: November 12, 2025
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

ZA (3); TH (1)