Rifapentine and Isoniazid TB Preventive Therapy (3HP) for Children Taking Dolutegravir-based Antiretroviral Treatment (DOLPHIN KIDS)

NCT05122767 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: IRB00280272
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

Brief Summary

Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (VL) (\< 50 copies/mL) and an indication for tuberculosis (TB) preventive treatment (TPT), will be switched to dolutegravir (DTG) with tenofovir/emtricitabine (TDF/FTC), tenofovir/lamivudine (TDF/3TC), abacavir/lamivudine (ABC/3TC) or zidovudine/lamivudine (AZT/3TC) in accordance with South African National HIV Guidelines. Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI antiretroviral therapy (ART) regimen for at least four weeks (and have not received efavirenz, or nevirapine or lopinavir/ritonavir for at least four weeks) who have an undetectable HIV viral load may also participate.

Conditions

Tuberculosis; HIV

Keywords

TB; 3HP; pharmacokinetic; rifapentine; isoniazid; dolutegravir

Outcome Measures

Primary Outcomes (5)

• PK sampling of Dolutegravir - ka parameter

  Absorption rate constant (ka) in the presence or absence of once weekly HP (all groups)

  PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial

• PK sampling of Dolutegravir - Vd parameter

  Volume of distribution in the presence or absence of once weekly HP (all groups)

  PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial

• PK sampling of Dolutegravir - Cl/F parameter

  Oral clearance in the presence or absence of once weekly HP (all groups)

  PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial

• PK sampling of Dolutegravir - AUC parameter

  Area under the plasma drug concentration-time curve in the presence or absence of once weekly HP (all groups)

  PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial

• PK sampling of Dolutegravir - Ctau parameter

  Trough concentration in the presence or absence of once weekly HP (all groups)

  PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial

Secondary Outcomes (6)

• Adverse Events

  Adverse events to be collected from Week 1 through Week 24, to be reported throughout the trial

• HIV-1 RNA viral load

  HIV viral load to be measured at Screening, and Weeks 7 and 24, to be reported at end of trial

• PK sampling of RPT - AUC parameter

  PK sampling at Week 12 (Day 78) to be reported at end of trial

• PK sampling of RPT - Cmax parameter

  PK sampling at Week 12 (Day 78) to be reported at end of trial

• PK sampling of RPT - Ctau parameter

  PK sampling at Week 12 (Day 78) to be reported at end of trial

Study Arms (1)

Single Arm in 4 groups

EXPERIMENTAL

There will be four groups. Group 1a and Group 1b will provide semi-intensive PK data and safety monitoring to allow for comparison of twice-daily dolutegravir exposures together with HP vs. when DTG is given alone. Group 2a and Group 2b will provide semi-intensive PK data and safety monitoring for either twice-daily or once-daily dolutegravir together with HIV vs when DTG is given alone. All groups will provide safety and tolerability data, HIV virologic outcome data, and information about dolutegravir and rifapentine PK.

Drug: Dolutegravir; Drug: 3HP

Interventions

Dolutegravir DRUG

Groups 1a/1b: Participants will take the FDA-approved weight-based DTG once daily + either TDF/FTC, TDF/3TC, ABC/3TC or AZT/3TC x 4 weeks. During HP treatment and for two weeks afterward, DTG dose will be increased to twice daily. Participants will continue with the NRTI regimen they have previously tolerated, except where their age and weight allow them to transition from either AZT or ABC to TDF, as per South African National ART Guidelines. HLA-B\*5701 screening will therefore not be performed, as children will be currently taking and tolerating an ABC-containing regimen at enrolment. If any clinically suspected hypersensitivity reaction to ABC is suspected by history, ABC will not be continued. Groups 2a/2b: Participants will take weight-based DTG dosing twice or once daily, depending on the results of the modelled data for the Group 1a (for Group 2a) and/or Group 1b (for Group 2b) participants in the interim analysis.

Single Arm in 4 groups

3HP DRUG

3HP Dosing is by Age and Weight Children 2-15 years of age: 10-15kg (P 300mg, H 300mg); 16-23kg (P 450mg, H 500mg); 24-30kg (P 600mg, H 600mg); 31-34kg (P 750mg, H 700mg). Children 15-17 years, \>=30kg (P 900mg, H 900mg)

Single Arm in 4 groups

Eligibility Criteria

• Age: 3 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 3 months through 17 years
• Weight \> 3 kg
• Documented HIV infection by DNA polymerase chain reaction (PCR) or plasma RNA-PCR if \<18 months and by HIV-ELISA if 18 months and confirmed with a DNA PCR or RNA-PCR from an independent sample
• Undetectable HIV-1 viral load

You may not qualify if:

• Confirmed or suspected TB disease (evidenced by symptoms and/or clinical exam findings and/or chest radiographic findings suggestive of TB, positive mycobacterial culture or molecular TB testing, or currently on TB treatment for active TB disease)
• Likely to move from the study area during the study period
• Known exposure to TB cases with known or suspected resistance to isoniazid or rifampicin in the source case
• TB treatment within the past year
• Prior completion of a TPT course without re-exposure to persons with infectious TB since TPT completion
• Receipt of once-daily INH for \>30 days that was given for at least 14 consecutive days in the 30 days prior to enrolment.
• Sensitivity or intolerance to dolutegravir, isoniazid, or rifamycins
• Suspected acute hepatitis or known chronic or unstable liver disease\^; HBsAg positivity or anti-hepatitis A virus (HAV) Immunoglobulin M (IgM) antibody; any infant born to a Hepatitis C positive mother in whom in utero infection in the infant is unknown or under evaluation
• 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
• Estimated creatinine clearance \< 60 ml/min (Bedside Schwartz formula)\*
• Pregnancy or breastfeeding (infant of a breastfeeding mother is allowed)
• Women of childbearing potential who are unable or unwilling to use two forms of contraception\*\*
• Weight for age Z score below 2 or severe clinical malnutrition

Sponsors & Collaborators

• The Aurum Institute NPC: lead
• Johns Hopkins University: collaborator

Study Sites (2)

The Aurum Institute: Pretoria Clinical Research Centre

Pretoria, Gauteng, 0087, South Africa

Location

Peri Natal HIV Research Unit - Klerksdorp Tshepong Hospital

Klerksdorp, North West, 2571, South Africa

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Nicole Salazar-Austin

  JHU SOM Ped Infectious Disease

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (\< 50 copies/mL) and an indication for TPT, will be switched to DTG with tenofovir/emtricitabine (TDF/FTC), tenofovir/lamivudine (TDF/3TC), abacavir/lamivudine (ABC/3TC) or zidovudine/lamivudine (AZT/3TC) in accordance with South African National HIV Guidelines. Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least four weeks (and have not received efavirenz, or nevirapine or lopinavir/ritonavir for at least four weeks) who have an undetectable HIV viral load may also participate.

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: November 17, 2021
• Study Start: May 24, 2023
• Primary Completion: July 4, 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 (2)