Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 3HP-MOMS-AUR1-6-351 | Other Identifier | The Aurum Institute |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Johns Hopkins University | OTHER |
| Weill Medical College of Cornell University | OTHER |
| University of Washington | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: One month of daily isoniazid and rifapentine (4 weeks) | Experimental |
|
|
| Arm 2: Three months of once-weekly isoniazid and rifapentine (12 weeks) | Experimental |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rifapentine | Drug | As included in arm/group description |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| HIV-1 RNA viral load- maternal | Maternal HIV-1 RNA viral load (copies/ml) (both groups) | 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Dr Vaneshree Govender | Aurum Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| FAMily Centre for Research with Ubuntu (FAMCRU) | Cape Town | Cape Town | 7505 | South Africa | ||
| The Aurum Institute: Tembisa Clinical Research Centre |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Participants will be randomized 1:1 to receive either 1HP or 3HP
Not provided
Not provided
Not provided
Not provided
|
| Isoniazid | Drug | As included in arm/group description |
|
|
Dose options for DTG with 1HP or 3HP derived by simulation using nonlinear mixed effects models (both groups)
| 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 | Area under curve (AUC) in participants taking 1HP (Group 1) | PK sampling at Week 3 (Day 17 ) to be reported at end of trial |
| PK sampling of RPT - Ctau parameter | Trough concentration (Ctau) in participants taking 1HP (Group 1) | PK sampling at Week 3 (Day 17 ) to be reported at end of trial |
| Adverse Events- maternal | Grade 3 or higher maternal adverse events (AE) (all groups) | from study entry at Week 0 through post partum Week 12, to be reported at end of trial |
| Adverse Events- pregnancy | Grade 3 or higher pregnancy adverse events (AE) (all groups) | from study entry at Week 0 through post partum Week 12, to be reported at end of trial |
| Adverse Events- infant | Grade 3 or higher infant adverse events (AE) (all groups) | from Delivery through post partum Week 24, to be reported at end of trial |
| HIV infection- infant | Infant HIV infection (all groups) | from Delivery through post partum Week 24, to be reported at end of trial |
| Infant growth parameters- HAZ | Height-for-age z-score (all groups) | from Delivery through post partum Week 24, to be reported at end of trial |
| Infant growth parameters- WAZ | Weight-for-age z-score (WAZ) (all groups) | from Delivery through post partum Week 24, to be reported at end of trial |
| Infant growth parameters- HCAZ | Head circumference-for-age z-score (HCAZ) (all groups) | from Delivery through post partum Week 24, to be reported at end of trial |
| TB disease-maternal | confirmed maternal TB disease (all groups) | from study entry at Week 0 through post partum Week 24, to be reported at end of trial |
| TB disease-infant | confirmed or suspected infant TB disease (all groups) | from Delivery through post partum Week 24, to be reported at end of trial |
| Treatment adherence- HP | Proportion of doses taken for 1HP and 3HP regimens | from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 16 weeks of 3HP (Group 2) , to be reported at end of trial |
| Tembisa |
| Gauteng |
| 1632 |
| South Africa |
| Peri Natal HIV Research Unit - Klerksdorp Tshepong Hospital | Klerksdorp | North West | 2571 | South Africa |
| ID | Term |
|---|---|
| D006679 | HIV Seropositivity |
| D055985 | Latent Tuberculosis |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D000085343 | Latent Infection |
Not provided
Not provided
| ID | Term |
|---|---|
| C018421 | rifapentine |
| D007538 | Isoniazid |
| ID | Term |
|---|---|
| D006834 | Hydrazines |
| D009930 | Organic Chemicals |
| D007539 | Isonicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided