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)

NCT04295772 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 8591A-028MK-8591A-0282019-003597-10
• Study Type: interventional
• Target: 42
• Locations: 5 countries
• Sites: 17

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (11)

• Area Under the Plasma Drug Concentration-time Curve From 0 to 24 Hours Post-dose (AUC0-24) of Islatravir (ISL)

  The AUC0-24 of ISL in plasma was determined at steady state.

  Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28

• Maximum Plasma Concentration (Cmax) of ISL

  The Cmax of ISL in plasma was determined at steady state.

  Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28

• Time to Reach Maximum Plasma Concentration (Tmax) of ISL

  The Tmax of ISL in plasma was determined at steady state.

  Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28

• Apparent Plasma Terminal Half-life (t½) of ISL

  The t½ of ISL in plasma was determined at steady state.

  Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28

• Apparent Total Clearance From Plasma (CL/F) of ISL

  The CL/F of ISL from plasma was determined at steady state.

  Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28

• Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL

  The Vz/F of ISL was determined at steady state.

  Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28

• AUC0-last of ISL-triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMCs)

  The AUC0-24 of ISL-TP in PBMCs was determined at steady state.

  Pre-dose, and 4 and 24 hours post-dose on Day 28

• Cmax of ISL-TP in PBMCs

  The Cmax of ISL-TP in PBMCs was determined at steady state.

  Pre-dose, and 4, and 24 hours post-dose on Day 28

• C24 of ISL-TP in PBMCs

  The C24 of ISL-TP in PBMCs was determined at steady state.

  24 hours post-dose on Day 28

• Number of Participants Experiencing ≥1 Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to 24 weeks

• Number of Participants Discontinuing From Study Treatment Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to 24 weeks

Secondary Outcomes (9)

• Percentage of Virologically Suppressed (VS) Participants With HIV-1 Ribonucleic Acid (RNA) ≥50 Copies/mL

  Week 24

• Percentage of VS Participants With HIV-1 RNA <50 Copies/mL

  Week 24

• Percentage of Treatment Naive (TN) Participants With HIV-1 RNA <50 Copies/mL

  Week 24

• Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-cells in VS Participants

  Baseline (Day 1) and Week 24

• Change From Baseline in CD4+ T-cells in TN Participants

  Baseline (Day 1) and Week 24

Study Arms (1)

DOR/ISL

EXPERIMENTAL

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

Drug: DOR/ISL

Interventions

DOR/ISL DRUG

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

Also known as: MK-8591A, Doravirine/islatravir

DOR/ISL

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• Is female and expecting to conceive or donate eggs at any time during the study.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (17)

Children's National Medical Center ( Site 1816)

Washington D.C., District of Columbia, 20010, United States

Location

Emory Children's Center ( Site 1805)

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University ( Site 1800)

Baltimore, Maryland, 21287, United States

Location

Duke University ( Site 1807)

Durham, North Carolina, 27705, United States

Location

Azienda Ospedaliera Luigi Sacco ( Site 1300)

Milan, 20157, Italy

Location

IRCCS Ospedale Pediatrico Bambino Gesu ( Site 1301)

Roma, 00165, Italy

Location

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

Krasnoyarsk, Krasnoyarsk Krai, 660049, Russia

Location

Infectious Clinical Hospital #2 ( Site 1501)

Moscow, Moscow, 105275, Russia

Location

FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 1500)

Saint Petersburg, Sankt-Peterburg, 196645, Russia

Location

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

Saratov, Saratov Oblast, 410009, Russia

Location

Perinatal HIV Research Unit ( Site 1902)

Johannesburg, Gauteng, 1864, South Africa

Location

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

Johannesburg, Gauteng, 2000, South Africa

Location

Empilweni Services and Research Unit ( Site 1904)

Johannesburg, Gauteng, 2093, South Africa

Location

King Edward Hospital ( Site 1900)

Durban, KwaZulu-Natal, 4001, South Africa

Location

Chulalongkorn University ( Site 1602)

Bangkok, Bangkok, 10330, Thailand

Location

Siriraj Hospital ( Site 1601)

Bangkok, Bangkok, 10700, Thailand

Location

Research Institute for Health Sciences ( Site 1603)

Chiang Mai, 50200, Thailand

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

doravirine; islatravir

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 4, 2020
• Study Start: November 26, 2020
• Primary Completion: December 21, 2021
• Study Completion: January 25, 2023
• Last Updated: January 31, 2024
• Results First Posted: February 24, 2023

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); ZA (4); US (4); RU (4); TH (3)