Phase 2
Completed N=42
Doravirine/Islatravir (DOR/ISL) in Pediatric Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are <18 Years of Age and Weigh ≥35 kg (MK-8591A-028)
Source: ClinicalTrials.gov NCT04295772 ↗Enrolled (actual)
42
Serious AEs
1.8%
Results posted
Feb 2023
Primary outcomePrimary: Area Under the Plasma Drug Concentration-time Curve From 0 to 24 Hours Post-dose (AUC0-24) of Islatravir (ISL) — 0.114 hr*µmol/L
Summary
This is a phase 2, single-group, multi-site, open-label study of an islatravir/doravirine (ISL/DOR, MK-8591A) fixed dose combination (FDC) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in pediatric participants who are virologically suppressed (VS) on antiretroviral therapy (ART) for ≥3 months or are treatment-naive (TN). The primary purposes of the study are 1) to examine the steady-state pharmacokinetics (PK) of ISL in plasma; 2) the steady-state PK of ISL-triphosphate (ISL-TP) in peripheral blood mononuclear cells (PBMCs); and 3) to examine the safety and tolerability of ISL/DOR.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Drug Concentration-time Curve From 0 to 24 Hours Post-dose (AUC0-24) of Islatravir (ISL) |
0.114 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of ISL |
0.0245 | — |
| PRIMARY Time to Reach Maximum Plasma Concentration (Tmax) of ISL |
1.00 | — |
| PRIMARY Apparent Plasma Terminal Half-life (t½) of ISL |
16.5 | — |
| PRIMARY Apparent Total Clearance From Plasma (CL/F) of ISL |
22.5 | — |
| PRIMARY Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL |
536 | — |
| PRIMARY AUC0-last of ISL-triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMCs) |
52.3 | — |
| PRIMARY Cmax of ISL-TP in PBMCs |
2.87 | — |
| PRIMARY C24 of ISL-TP in PBMCs |
2.05 | — |
| PRIMARY Number of Participants Experiencing ≥1 Adverse Event (AE) |
21; 2 | — |
| PRIMARY Number of Participants Discontinuing From Study Treatment Due to an AE |
0; 0 | — |
| SECONDARY Percentage of Virologically Suppressed (VS) Participants With HIV-1 Ribonucleic Acid (RNA) ≥50 Copies/mL |
2.9 | — |
| SECONDARY Percentage of VS Participants With HIV-1 RNA <50 Copies/mL |
94.1 | — |
| SECONDARY Percentage of Treatment Naive (TN) Participants With HIV-1 RNA <50 Copies/mL |
100.0 | — |
| SECONDARY Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-cells in VS Participants |
-112.1 | — |
| SECONDARY Change From Baseline in CD4+ T-cells in TN Participants |
705.0 | — |
| SECONDARY Incidence of Viral Drug Resistance to DOR |
0; 0 | — |
| SECONDARY Incidence of Viral Drug Resistance to ISL |
0; 0 | — |
| SECONDARY Palatability of DOR/ISL Tablet |
0; 0; 0; 0; 2; 0 | — |
| SECONDARY Acceptability of DOR/ISL Tablet |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Is HIV-1 positive, is <18 years of age, and weighs ≥35 kg at screening.
- VS Participants: Is HIV-1 positive at Screening with plasma HIV-1 RNA <50 copies/mL and has been receiving continuous, stable oral 2-drug or 3-drug combination ART ± PK booster with documented viral suppression for ≥3 months prior to providing documented informed consent/assent and has no history of prior virologic treatment failure on any past or current regimen.
- TN Participants: Is HIV-1 positive at Screening with plasma HIV-1 RNA ≥500 copies/mL and is naive to ART defined as having received <=10 days of prior therapy with any antiretrovirals following HIV-1 diagnosis other than pre-exposure prophylaxis (PrEP) or potentially exposed person (PEP).
- If female, is not pregnant or breastfeeding, and is either 1) not a woman of childbearing potential (WOCBP) or 2) is a WOCBP and is using acceptable contraception or is abstinent.
Exclusion Criteria
- Has HIV-2 infection.
- Has hypersensitivity or other contraindication to any of the components of the study drugs as determined by the investigator.
- Has an active diagnosis of hepatitis due to any cause, including active hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive).
- Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma.
- Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate.
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 45 days prior to Day 1 through the study treatment period.
- Is currently taking long-acting cabotegravir-rilpivirine.
- Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period.
- Has a documented or known virologic resistance to DOR/ISL (DOR resistance substitutions in reverse transcriptase: V106A/M, V108I, Y188L, H221Y, P225H, F227C/L, M230I/L, L234I, P236L, or Y318F; ISL resistance substitution in reverse transcriptase: M184V/I).
- Has exclusionary laboratory values.
- Is female and expecting to conceive or donate eggs at any time during the study.
Data sourced from ClinicalTrials.gov (NCT04295772). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.