DOR/ISL in heavily treatment-experienced participants

JRCT ID: jRCT2080225147

Registered date:30/03/2020

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: HIV-1 infection
• Date of first enrollment: 13/05/2020
• Target sample size: 100
• Countries of recruitment: Japan,Asia except Japan,North America,South America,Europe,Oceania,Africa
• Study type: Interventional

Intervention(s)

- Part1: Arm1
HTE participants with HIV-1 infection take ISL 0.75 mg once daily (QD) in combination with failing ART from Day 1 to Day 7
- Part1: Arm2
HTE participants with HIV-1 infection take DOR 100 mg QD in combination with failing ART from Day 1 to Day 7
- Part1: Arm3
HTE participants with HIV-1 infection take 100 mg DOR/0.75 mg ISL FDC QD in combination with failing ART from Day 1 to Day 7
- Part1: Arm4
HTE participants with HIV-1 infection take placebo QD in combination with failing ART from Day 1 to Day 7

- Part2:
100 mg DOR/0.75 mg ISL fixed dose combination (FDC) QD + optimized background therapy from Day 8 to Week 97.

Outcome(s)

Primary Outcome

- To evaluate the antiretroviral activity of DOR/ISL compared to placebo, each given in combination with failing ART as assessed by the percentage of participants achieving >=0.5 log10 decrease in HIV 1 RNA from study baseline (Day 1) to Day 8 (Part 1).
The change from baseline in HIV-1 RNA will be determined at the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay with a lower limit of detection (LLOD) of 40 copies/mL.
- To evaluate the safety and tolerability of DOR/ISL as assessed by review of the accumulated safety data through Week 25 and Week 49.
- AEs
- AEs leading to discontinuation of study intervention

Secondary Outcome

- To evaluate the antiretroviral activity of ISL and DOR, each compared to placebo, when each is given in combination with failing ART, as assessed by the percentage of participants achieving >=0.5 log10 decrease in HIV 1 RNA from study baseline (Day 1) to Day 8 (Part 1).
The change from baseline in HIV-1 RNA will be determined at the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay with a lower limit of detection (LLOD) of 40 copies/mL.
- To further evaluate the antiretroviral activity of DOR/ISL, ISL, and DOR each compared to placebo, when each is given in combination with failing ART (Part 1) .
The change from baseline in HIV-1 RNA will be determined at the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay with a lower limit of detection (LLOD) of 40 copies/mL.
- mean change in HIV-1 RNA from study baseline (Day 1) to Day 8
- percentage of participants achieving >=1.0 log10 decrease in HIV-1 RNA from study baseline (Day 1) to Day 8
- To further evaluate the antiretroviral activity of DOR/ISL compared to ISL and DOR, when each is given in combination with failing ART (Part 1)
- percentage of participants achieving >=0.5 log10 decrease in HIV-1 RNA from study baseline (Day 1) to Day 8
- mean change in HIV-1 RNA from study baseline (Day 1) to Day 8
- percentage of participants achieving >=1.0 log10 decrease in HIV-1 RNA from study baseline (Day 1) to Day 8
- To evaluate the antiretroviral activity of DOR/ISL + OBT in Part 2 as assessed by the following at Week 25, Week 49, and Week 97 compared to study baseline (Day 1) and Part 2 baseline (Day 8):
- percentage of participants achieving >=0.5 log10 decrease in HIV-1 RNA
- percentage of participants achieving >=1.0 log10 decrease in HIV-1 RNA
- mean change in HIV-1 RNA
- percentage of participants achieving HIV-1 RNA <200 copies/mL
- percentage of participants achieving HIV-1 RNA <50 copies/mL
- percentage of participants achieving HIV-1 RNA <40 copies/mL
- To evaluate the development of viral drug resistance to DOR, ISL, or components of OBT through the study duration (Part 1 and Part 2).
- To evaluate the impact of study baseline (Day 1) antiviral resistance on virologic outcome at Week 25, Week 49, and Week 97 (Part 2).
- To evaluate the change in CD4+ T cell counts from both study baseline (Day 1) and Part 2 baseline (Day 8) at Week 25, Week 49, and Week 97 (Part 2).

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Is HIV-1 positive.
- Has been receiving the same baseline ART for >=3 months prior to signing the Informed Consent Form/Assent Form.
- Weighs >=35 kg.
- Has at least triple-class resistance (must include nucleoside reverse transcriptase inhibitor [NRTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], and resistance to either protease inhibitor (PI) or integrase strand transfer inhibitor (InSTI), based on central laboratory-based resistance or proviral DNA resistance testing at the Screening Visit, or historical resistance testing within 12 months of screening.
- Has =<2 fully active antiretroviral drugs remaining among all antiretroviral classes that can be effectively combined to form a viable regimen based on resistance, tolerability, safety, drug access, or acceptability to participant.
- If female, is not pregnant or breastfeeding, and is: 1) not a woman of childbearing potential (WOCBP); 2) a WOCBP and uses an acceptable method of contraception/is abstinent; or 3) a WOCBP and has a negative pregnancy test within 24 hours of the first dose of study medication.

Exclude criteria

- Has HIV type 2 (HIV-2) infection.
- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
- Has hepatitis B virus (HBV) co-infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive) and is not currently being treated for HBV.
- Has a history or current evidence of any condition, therapy (including active TB co-infection), laboratory abnormality or other circumstance (including drug or alcohol abuse or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with study participation for the full study duration.
- Is taking or is anticipated to require any of the prohibited therapies from the Screening Visit and throughout the study treatment period.
- Is taking DOR as part of his/her current failing antiretroviral regimen.
- Is taking efavirenz (EFV), etravirine, or nevirapine.
- Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from the Screening Visit through the study treatment period.
- Is female and is expecting to conceive or donate eggs at any time during the study.

Related Information

• Primary Sponsor: MSD K.K.
• Secondary ID(s): NCT04233216,JapicCTI-205243