Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03435146 |
Other study ID # |
3HP DTG AUR1-6-212 IMPAACT4TB |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 1/Phase 2
|
First received |
|
Last updated |
|
Start date |
January 18, 2018 |
Est. completion date |
December 7, 2022 |
Study information
Verified date |
January 2023 |
Source |
The Aurum Institute NPC |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Single-arm, single-center, Phase I/II clinical trial, in four groups. Individuals with HIV
infection taking Efavirenz (EFV) and two nucleoside reverse transcriptase inhibitors (NRTI)
who have undetectable (Groups 1 and 2) or detectable (Group 3 and 4) HIV viral load and an
indication for TPT, will be switched to DTG with tenofovir/emtricitabine (Groups 1 and 2) or
lamivudine/tenofovir (Groups 3 and 4). Group 1 and 2 will receive weekly HP for 12 total
doses starting 8 weeks after initiating DTG. Individuals who are on an existing DTG-based
plus two NRTI ART regimen for at least eight weeks (and have not received efavirenz or
nevirapine for at least two months) who have an undetectable HIV viral load may also
participate. Individuals with HIV infection who are ART treatment naïve at any HIV viral load
level and have an indication for TPT will start DTG and be enrolled to receive standard IPT
(Group 3) or HP (Group 4) initiated at the same time as DTG. Group 3 and 4 will be enrolled
after follow up of Group 1 and 2 has been completed.
Description:
Group 1 (n=30): The first 12 participants (Group 1A) will take dolutegravir 50 milligrams
(mg) once daily (with tenofovir/emtricitabine) from Days 1-57. Semi-intensive PK sampling for
dolutegravir will be performed on Day 57. Participants will continue once-daily dolutegravir
and will receive once-weekly HP for 12 total doses beginning on Day 58. Semi-intensive PK
sampling for dolutegravir will be performed on Day 72 (with the 3rd dose of HP) and Day 108
(following the 8th dose of HP). Trough concentrations (CT) will be measured on Days 59, 74,
and 78. PK assessments will be performed at weeks 9 and 11 for rifapentine and at week 11 for
isoniazid. VL will be measured at baseline and weeks 11 and 24. Safety labs (complete blood
count (CBC), urea and electrolytes (U&E) and creatinine and liver function tests (LFT)) will
be obtained at baseline, and weeks 9, 11, 13, 16, 20 and 24.
After the 12 Group 1A participants have completed the second semi-intensive PK visit, an
interim PK, safety, and VL assessment will be performed to ensure that the 50 mg once daily
dose is safe and meets PK targets. The subsequent 18 participants in Group 1 (Group 1B) will
receive either dolutegravir 50 mg or a higher dose of dolutegravir, if dose adjustment is
required (e.g. dolutegravir 50 mg twice daily just on HP dosing days, dolutegravir 50 mg
twice daily seven days a week, etc.) A second interim evaluation focused on PK will occur
after all Group 1B participants have completed the Week 11 semi-intensive PK visit. This
evaluation will include all PK data from Group 1A, who will have completed their Week 16
semi-intensive PK visit plus PK data from Group 1B up to and including the Week 11
semi-intensive PK visit.
A third interim evaluation focused on safety and virologic response will occur after all
participants (Groups 1A, 1B, and 2) have completed the Week 11 visit. This evaluation will
include all safety data and HIV viral load information collected up until that point from all
participants.
Group 2 (n=30): These participants will receive dolutegravir and HP at the same doses and
dose schedule as the participants in Group 1B. They will undergo safety assessments at
baseline and weeks 9, 11, 13, 16, 20 and 24; HIV VL assessments will be performed at baseline
and weeks 11 and 24. Sparse (trough) PK samples for dolutegravir will be collected on two
occasions.
Group 3 (n=25): The next 25 participants who are ART treatment naïve will start dolutegravir
50 milligrams (mg) once daily (with tenofovir/lamivudine on study Day 0. Sparse PK sampling
for trough concentrations (CT) of dolutegravir will be performed on Day 1 (24 hours after
taking the first dose of DTG, and before taking the first dose of standard isoniazid). Sparse
PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 24 (Week
3), to parallel 721 hours after the 3rd dose of HP. The final sparse PK sampling for trough
concentrations (CT) of dolutegravir will be performed on Day 59 (Week 8), to parallel 721
hours after the 8th dose of HP. HIV VL will be measured at screening, and Weeks 3, 8, 12, 16,
and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U&E) and creatinine
and liver function tests (LFT)) will be obtained at baseline. Creatinine will be repeated at
Weeks 2, 4, 8, 12, 16 and 24 and LFTs will be repeated at weeks 4, 8, and 12.
Group 4 (n=50): After Group 3 is fully enrolled, another group of 50 participants who are ART
treatment naïve will start dolutegravir 50 milligrams (mg) once daily (with
tenofovir/lamivudine) on Day 0. They will begin TPT with once weekly HP the day after
starting DTG, on Day 1. Sparse PK sampling for trough concentrations (CT) dolutegravir will
be performed on Day 1 (24 hours after the first dose of DTG, before the first dose of HP).
Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 24
(721 hours after the third dose of HP). Sparse PK sampling for trough concentrations (CT) of
dolutegravir will be performed on Day 59 (721 hours after the eighth dose of HP). HIV VL will
be measured at screening, and Weeks 3, 8, 12, 16, and 24. Safety labs (complete blood count
(CBC), urea and electrolytes (U&E) and creatinine and liver function tests (LFT)) will be
obtained at baseline. Creatinine will be repeated at Weeks 2, 4, 8, 12, 16, and 24, and LFTs
will be repeated at weeks 4, 8, and 12.
1 (+/- 24 hours)