Doravirine (DOR) in Human Immunodeficiency Virus (HIV)-Infected Children Aged 4 Weeks to <12 Years and <45 kg (MK-1439-066)

NCT04375800 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 1439-066MK-1439-0662019-003955-13
• Study Type: interventional
• Target: 84
• Locations: 6 countries
• Sites: 24

Brief Summary

This is a single-group, open-label, multi-site study in pediatric participants with human immunodeficiency virus type 1 (HIV-1) infection, aged 4 weeks to \<12 years and weighing \<45 kg, who are treatment-naive (TN) or have been virologically suppressed (VS) on stable combination antiretroviral therapy (cART) for ≥3 months with no history of treatment failure. The primary objectives are:

• To evaluate the steady state pharmacokinetics (PK) of doravirine (DOR) \[MK-1439\] when given in combination with 2 nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs) or as part of the fixed-dose combination (FDC) of DOR/lamivudine (3TC)/tenofovir disproxil fumarate (TDF) in participants ≥6 to \<12 years and weighing ≥14 to \<45 kg.
• To evaluate the safety and tolerability of DOR when given with 2 NRTIs or as part of the FDC of DOR/3TC/TDF, in participants ≥6 to 12 years and weighing ≥14 to \<45 kg, through Week 24.

Conditions

Human Immunodeficiency Virus (HIV) Infection

Outcome Measures

Primary Outcomes (13)

• Area Under the Concentration-Time Curve (AUC) From 0 to 24 Hours Postdose (AUC0-24hr) of Doravirine (DOR) Following Once-Daily Dosing in Plasma at Steady-State

  Per protocol, intensive pharmacokinetic (PK) sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr.

  Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

• Maximum Concentration (Cmax) of DOR Following Once-Daily Dosing in Plasma at Steady-State

  Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax.

  Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

• Concentration at 24 Hours (C24) of DOR Following Once-Daily Dosing in Plasma at Steady-State

  Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine C24.

  Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

• Time to Maximum Concentration (Tmax) of DOR Following Once-Daily Dosing in Plasma at Steady-State

  Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Tmax.

  Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

• AUC From 0 to 12 Hours Postdose (AUC0-12hr) of DOR Following Twice-Daily Dosing in Plasma at Steady-State

  Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine AUC0-12hr.

  Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose

• Cmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State

  Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine Cmax.

  Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose

• Concentration at 12 Hours (C12) of DOR Following Twice-Daily Dosing in Plasma at Steady-State

  Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine C12.

  Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose

• Tmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State

  Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine Tmax.

  Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose

• Percentage of Participants With ≥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 interventions.

  Up to 24 weeks

• Percentage of Participants With a Grade 3 or 4 AE

  Grade 3 or 4 AEs are "severe symptoms that cause inability to perform usual social and functional activities with intervention or hospitalization indicated" (Grade 3), or "potentially life-threatening events" (Grade 4).

  Up to 24 weeks

• Percentage of Participants With Events of Death

  The percentage of participants with events of death at Week 24 will be reported.

  Up to 24 weeks

• Percentage of Participants Discontinuing From Study Intervention 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 interventions.

  Up to 24 weeks

• Percentage of Participants Discontinuing From Study Intervention Due to a Drug-Related AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered to be related to the study interventions.

  Up to 24 weeks

Secondary Outcomes (35)

• Plasma Concentration of DOR

  Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks

• Plasma Concentration of Lamivudine (3TC) Following Once-Daily Dosing of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) as an Age-Appropriate Fixed-Dose Combination (FDC)

  Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks

• Plasma Concentration of Tenofovir (TFV) Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC

  Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks

• AUC0-24hr of 3TC Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC

  Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

• AUC0-24hr of TFV Following Once-Daily Dosing of DOR/3TC/TDF as an Age-Appropriate FDC

  Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose

Study Arms (1)

Doravirine as a single entity plus 2 NRTIs or Doravirine as a FDC with 3TC and TDF

EXPERIMENTAL

Participants receive doravirine (DOR) at 7.2 mg to 100 mg, based on weight, PLUS 2 nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs), based on local label, for 96 weeks, OR a fixed-dose combination (FDC) of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF), based on weight, for 96 weeks.

Drug: Doravirine; Drug: 2 NRTIs; Drug: DOR/3TC/TDF

Interventions

Doravirine DRUG

Administered orally

Also known as: MK-1439

Doravirine as a single entity plus 2 NRTIs or Doravirine as a FDC with 3TC and TDF

2 NRTIs DRUG

Administered orally

Doravirine as a single entity plus 2 NRTIs or Doravirine as a FDC with 3TC and TDF

DOR/3TC/TDF DRUG

Administered orally

Also known as: MK-1439A

Doravirine as a single entity plus 2 NRTIs or Doravirine as a FDC with 3TC and TDF

Eligibility Criteria

• Age: 4 Weeks - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Has human immunodeficiency virus type 1 (HIV-1) infection confirmed at screening
• Has appropriate treatment history defined as treatment-naïve (TN) or with documented virologic suppression (HIV-1 ribonucleic acid \[RNA\] \<50 copies/mL) on stable combination antiretroviral therapy (cART) for ≥3 months
• Body weight is \>3 kg to \<45 kg
• If female, is not pregnant or breastfeeding, and one of the following applies:
• Is not a woman of childbearing potential (WOCBP)
• Is a WOCBP using an acceptable form of contraception, or is abstinent
• If a WOCBP must have a negative pregnancy test (urine or serum) within 24 hours of the first dose of study intervention
• Has completed the Week 96 visit
• Is considered, in the opinion of the investigator, to have derived benefit from treatment with doravirine (DOR) plus the 2 nucleoside/nucleotide analog reverse transcriptase inhibitor (NRTIs) selected by the investigator, or doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF), by Week 96 of the study
• Is considered, in the opinion of the investigator, to be a clinically appropriate candidate for additional treatment with DOR regimens (DOR plus 2 NRTIs selected by the investigator or DOR/3TC/TDF)
• Understands the procedures in the study extension and has provided (or have the participant's legally acceptable representative, if applicable, provide) documented informed consent/assent to enter the study extension and continue treatment with DOR regimens (DOR plus 2 NRTIs selected by the investigator or DOR/3TC/TDF) until it is available locally in countries participating in the study or for up to an additional 224 weeks (whichever comes first)

You may not qualify if:

• Has evidence of renal disease
• Demonstrates evidence of liver disease
• Has clinical or laboratory evidence of pancreatitis
• Has any history of malignancy
• Has presence of any active acquired immunodeficiency syndrome (AIDS)-defining opportunistic Infection
• Has an active diagnosis of hepatitis, including hepatitis B co-infection
• Has current active tuberculosis and/or is being treated with a rifampicin-containing regimen
• Has a medical condition that precludes absorption or intake of oral pellets/granules
• Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound results of the study or interfere with participating for the entire duration of the study
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or other prohibited therapy
• 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 treatment period
• Has a documented or known virologic resistance to DOR
• Has any history of viremia (HIV RNA \>1000 copies/mL) after at least 3 months on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (24)

University of Colorado at Denver ( Site 0108)

Aurora, Colorado, 80045, United States

COMPLETED

Emory Children's Center ( Site 0103)

Atlanta, Georgia, 30322, United States

RECRUITING

Clinica Somer ( Site 1003)

Rionegro, Antioquia, 054040, Colombia

RECRUITING

Ciensalud Ips S A S ( Site 1001)

Barranquilla, Atlántico, 080020, Colombia

RECRUITING

CEIP - Centro de Estudios en Infectología Pediátrica ( Site 1002)

Cali, Valle del Cauca Department, 760042, Colombia

RECRUITING

Instituto Nacional de Pediatria ( Site 0701)

Coyoacán, Mexico City, 04530, Mexico

COMPLETED

Hospital Infantil de Mexico Federico Gomez ( Site 0702)

Mexico City, Mexico City, 06720, Mexico

ACTIVE NOT RECRUITING

Unidad de Atencion Medica e Investigacion en Salud S.C. ( Site 0700)

Mérida, Yucatán, 97000, Mexico

COMPLETED

Kuzbasskiy Center for the Prevention and Control of AIDS ( Site 0506)

Kemerovo, Kemerovo Oblast, 650056, Russia

RECRUITING

Clinical Centre for Prevention and Control of AIDS ( Site 0504)

Krasnodar, Krasnodarskiy Kray, 350015, Russia

COMPLETED

Krasnoyarsk Regional Center for Prevention and Control of AIDS ( Site 0507)

Krasnoyarsk, Krasnoyarsk Krai, 660049, Russia

COMPLETED

Infectious Clinical Hospital #2 ( Site 0501)

Moscow, Moscow, 105275, Russia

COMPLETED

FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 0500)

Saint Petersburg, Sankt-Peterburg, 196645, Russia

RECRUITING

FARMOVS PTY LTD ( Site 0601)

Bloemfontein, Free State, 9301, South Africa

COMPLETED

Perinatal HIV Research Unit ( Site 0602)

Johannesburg, Gauteng, 1864, South Africa

RECRUITING

Wits Reproductive Health and HIV Institute (WRHI) ( Site 0603)

Johannesburg, Gauteng, 2001, South Africa

RECRUITING

Empilweni Services and Research Unit ( Site 0604)

Johannesburg, Gauteng, 2093, South Africa

COMPLETED

King Edward Hospital ( Site 0600)

Durban, KwaZulu-Natal, 4001, South Africa

RECRUITING

Family Clinic Research With UBUNTU ( Site 0605)

Cape Town, Western Cape, 7505, South Africa

RECRUITING

Be Part Yoluntu Centre ( Site 0606)

Paarl, Western Cape, 7626, South Africa

RECRUITING

Tsitsikamma Clinical Research Initiative (TCRI) ( Site 0607)

Plettenberg Bay, Western Cape, 6600, South Africa

COMPLETED

Siriraj Hospital ( Site 0901)

Bangkok, Bangkok, 10700, Thailand

RECRUITING

Research Institute for Health Sciences ( Site 0902)

Chiang Mai, 50200, Thailand

RECRUITING

Faculty of Medicine - Khon Kaen University ( Site 0903)

Khon Kaen, 40002, Thailand

RECRUITING

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

doravirine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

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: May 4, 2020
• First Posted: May 5, 2020
• Study Start: February 3, 2021
• Primary Completion (Estimated): November 12, 2028
• Study Completion (Estimated): April 11, 2034
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CO (3); ME (3); ZA (8); RU (5); US (2); TH (3)