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

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2

Conditions: Human Immunodeficiency Virus (HIV) Infection

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04375800

1439-066

MK-1439-066 (Other Identifier)

2019-003955-13 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

Participants who complete the Week 96 visit will be eligible to enroll in an Extension Study and receive DOR until it is commercially available, or for up to an additional 224 weeks (whichever comes first).

Enrollment: 84 estimated patients

Sex: All

Ages: 4 weeks to 11 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Study Extension Inclusion Criteria:

• 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)

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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84 participants in 1 patient group

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

Experimental group

Description:

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.

Treatment:

Drug: 2 NRTIs

Drug: DOR/3TC/TDF

Drug: Doravirine