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

ConditionHuman Immunodeficiency Virus (HIV) Infection

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age4-11

SponsorMerck Sharp & Dohme LLC

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Is not a woman of childbearing potential (WOCBP)

Disqualifiers

Has evidence of renal disease

Demonstrates evidence of liver disease

Has clinical or laboratory evidence of pancreatitis

Has any history of malignancy

Trial design

Design model

Single group

Treatments tested in this trial

Doravirine
Drug
Administered orally
2 NRTIs
Drug
Administered orally
DOR/3TC/TDF
Drug
Administered orally

Treatment groups

84 Participants

are divided into 1 treatment group

Group A: Doravirine as a single entity plus 2 NRTIs or Doravirine as a FDC with 3TC and TDFExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

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.

Time frame

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.

Time frame

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

Secondary outcomes

Plasma Concentration of DOR

Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks.

Time frame

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)

Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks.

Time frame

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

Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits up to 24 weeks.

Time frame

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

Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr of 3TC.

Time frame

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