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)

NCT ID: NCT04295772

Last Updated: 2024-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-26
• Study Completion Date: 2023-01-25

Brief 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.

Detailed Description

As of protocol amendment 03 (approved 08-Feb-2022), all participants have been discontinued from study therapy and will be switched to non-study antiretroviral therapy and monitored for safety. The present results cover data obtained through the cut-off date of 30-Mar-2022, and will be updated once monitoring is completed.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DOR/ISL

Pediatric participants with HIV-1 infection receive DOR/ISL for 96 weeks.

Group Type: EXPERIMENTAL

DOR/ISL

Intervention Type: DRUG

100 mg DOR/0.75 mg ISL FDC tablet taken once daily by mouth.

Interventions

DOR/ISL

100 mg DOR/0.75 mg ISL FDC tablet taken once daily by mouth.

Intervention Type: DRUG

Other Intervention Names

MK-8591A; Doravirine/islatravir

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.

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Children's National Medical Center ( Site 1816)

Washington D.C., District of Columbia, United States

Emory Children's Center ( Site 1805)

Atlanta, Georgia, United States

Johns Hopkins University ( Site 1800)

Baltimore, Maryland, United States

Duke University ( Site 1807)

Durham, North Carolina, United States

Azienda Ospedaliera Luigi Sacco ( Site 1300)

Milan, , Italy

IRCCS Ospedale Pediatrico Bambino Gesu ( Site 1301)

Roma, , Italy

Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 1507)

Krasnoyarsk, Krasnoyarsk Krai, Russia

Infectious Clinical Hospital #2 ( Site 1501)

Moscow, Moscow, Russia

FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 1500)

Saint Petersburg, Sankt-Peterburg, Russia

Saratov Regional Clinical Center for Prophylaxis and Control of AIDS ( Site 1505)

Saratov, Saratov Oblast, Russia

Perinatal HIV Research Unit ( Site 1902)

Johannesburg, Gauteng, South Africa

Wits Reproductive Health and HIV Institute (WRHI) ( Site 1903)

Johannesburg, Gauteng, South Africa

Empilweni Services and Research Unit ( Site 1904)

Johannesburg, Gauteng, South Africa

King Edward Hospital ( Site 1900)

Durban, KwaZulu-Natal, South Africa

Chulalongkorn University ( Site 1602)

Bangkok, Bangkok, Thailand

Siriraj Hospital ( Site 1601)

Bangkok, Bangkok, Thailand

Research Institute for Health Sciences ( Site 1603)

Chiang Mai, , Thailand

Countries

United States; Italy; Russia; South Africa; Thailand

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

MK-8591A-028

Identifier Type: OTHER

Identifier Source: secondary_id

2019-003597-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591A-028

Identifier Type: -

Identifier Source: org_study_id