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.
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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
84
University of Colorado at Denver ( Site 0108)
Aurora, Colorado, United States
COMPLETEDEmory Children's Center ( Site 0103)
Atlanta, Georgia, United States
RECRUITINGClinica Somer ( Site 1003)
Rionegro, Antioquia, Colombia
RECRUITINGCiensalud Ips S A S ( Site 1001)
Barranquilla, Atlántico, Colombia
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 24 weeks
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
AUC0-24hr of TFV 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 TFV.
Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose
Cmax 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 Cmax of 3TC.
Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
CEIP - Centro de Estudios en Infectología Pediátrica ( Site 1002)
Cali, Valle del Cauca Department, Colombia
COMPLETEDInstituto Nacional de Pediatria ( Site 0701)
Coyoacán, Mexico City, Mexico
COMPLETEDHospital Infantil de Mexico Federico Gomez ( Site 0702)
Mexico City, Mexico City, Mexico
ACTIVE_NOT_RECRUITINGUnidad de Atencion Medica e Investigacion en Salud S.C. ( Site 0700)
Mérida, Yucatán, Mexico
COMPLETEDKuzbasskiy Center for the Prevention and Control of AIDS ( Site 0506)
Kemerovo, Kemerovo Oblast, Russia
ACTIVE_NOT_RECRUITINGClinical Centre for Prevention and Control of AIDS ( Site 0504)
Krasnodar, Krasnodarskiy Kray, Russia
COMPLETED...and 14 more locations
Cmax of TFV 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 Cmax of TFV.
Time frame: Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose
Percentage of Participants With ≥1 AE at Week 48
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.
Time frame: Up to 48 weeks
Percentage of Participants With ≥1 AE at Week 96
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.
Time frame: Up to 96 weeks
Percentage of Participants With Grade 3 or 4 AE at Week 48
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).
Time frame: Up to 48 weeks
Percentage of Participants With Grade 3 or 4 AE at Week 96
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).
Time frame: Up to 96 weeks
Percentage of Participants With Events of Death at Week 48
The percentage of participants with events of death at Week 48 will be reported.
Time frame: Up to 48 weeks
Percentage of Participants With Events of Death at Week 96
The percentage of participants with events of death at Week 96 will be reported.
Time frame: Up to 96 weeks
Percentage of Participants Discontinuing From Study Intervention Due to AE at Week 48
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.
Time frame: Up to 48 weeks
Percentage of Participants Discontinuing from Study Intervention Due to AE at Week 96
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.
Time frame: Up to 96 weeks
Percentage of Participants Discontinuing From Study Intervention Due to Drug-Related AE at Week 48
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.
Time frame: Up to 48 weeks
Percentage of Participants Discontinuing From Study Intervention Due to Drug-Related AE at Week 96
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.
Time frame: Up to 96 weeks
Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL at Week 24
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 24 weeks
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 48 weeks
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 96 weeks
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 24
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 24 weeks
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 48 weeks
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 96 weeks
Percentage of Participants With HIV-1 RNA ≥50 copies/mL at Week 24
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 24 weeks
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 48 weeks
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Up to 96 weeks
Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 24
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Baseline (Day 1) and Week 24
Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 48
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Baseline (Day 1) and Week 48
Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 96
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a real-time PCR assay with a lower limit of detection of 40 copies/mL.
Time frame: Baseline (Day 1) and Week 96
Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 24
CD4+ T-cell counts will be performed at the central laboratory.
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in CD4+ T-Cell Counts at Week 48
CD4+ T-cell counts will be performed at the central laboratory.
Time frame: Baseline (Day 1) and Week 48
Change From Baseline in CD4+ T-Cell Counts at Week 96
CD4+ T-cell counts will be performed at the central laboratory.
Time frame: Baseline (Day 1) and Week 96
Viral Resistance-Associated Substitutions (RASs) to DOR or Other Treatment Components
The presence of viral RASs to DOR or other treatment components will be monitored for up to 96 weeks.
Time frame: Up to 96 weeks
Percentage of Participants Adhering to DOR or to the FDC of DOR/3TC/TDF
Adherence to DOR or to the FDC of DOR/3TC/TDF will be monitored for up to 96 weeks.
Time frame: Up to 96 weeks
Assessment of Palatability/Acceptability of Oral Pellets/Granules of DOR or the FDC of DOR/3TC/TDF
Palatability/acceptability will be based on scores on the 5-point facial hedonic scale (FHS). FHS scores will be tabulated and summarized by mean and standard deviation (SD), on Day 28. The highest possible FHS score is 5, with higher scores indicative of greater palatability.
Time frame: Day 28