Human Immunodeficiency Virus (HIV) Infection
Conditions
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.
Detailed 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).
Interventions
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Weeks to 11 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Events of Death | Up to 24 weeks | The percentage of participants with events of death at Week 24 will be reported. |
| 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 | Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose | Per protocol, intensive pharmacokinetic (PK) sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine AUC0-24hr. |
| Maximum Concentration (Cmax) of DOR Following Once-Daily Dosing in Plasma at Steady-State | Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax. |
| Concentration at 24 Hours (C24) of DOR Following Once-Daily Dosing in Plasma at Steady-State | Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine C24. |
| Time to Maximum Concentration (Tmax) of DOR Following Once-Daily Dosing in Plasma at Steady-State | Intensive pharmacokinetic sampling: at designated timepoints up to 24 hours postdose | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Tmax. |
| AUC From 0 to 12 Hours Postdose (AUC0-12hr) of DOR Following Twice-Daily Dosing in Plasma at Steady-State | Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose | Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine AUC0-12hr. |
| Cmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State | Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose | Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine Cmax. |
| Concentration at 12 Hours (C12) of DOR Following Twice-Daily Dosing in Plasma at Steady-State | Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose | Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine C12. |
| Tmax of DOR Following Twice-Daily Dosing in Plasma at Steady-State | Intensive pharmacokinetic sampling: at designated timepoints up to 12 hours postdose | Per protocol, intensive PK sampling includes multiple blood samples collected up to 12 hours postdose at a single visit to determine Tmax. |
| Percentage of Participants With ≥1 Adverse Event (AE) | Up to 24 weeks | 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. |
| Percentage of Participants With a Grade 3 or 4 AE | Up to 24 weeks | 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). |
| Percentage of Participants Discontinuing From Study Intervention Due to an AE | Up to 24 weeks | 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. |
| Percentage of Participants Discontinuing From Study Intervention Due to a Drug-Related AE | Up to 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of DOR | Sparse pharmacokinetic sampling: at designated timepoints up to 24 weeks | Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits 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 | Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits 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 | Per protocol, sparse PK sampling includes up to 2 blood samples collected at multiple visits 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 | 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. |
| 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 | 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. |
| Cmax 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax of 3TC. |
| Cmax 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 | Per protocol, intensive PK sampling includes multiple blood samples collected up to 24 hours postdose at a single visit to determine Cmax of TFV. |
| Percentage of Participants With ≥1 AE at Week 48 | Up to 48 weeks | 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. |
| Percentage of Participants With ≥1 AE at Week 96 | Up to 96 weeks | 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. |
| Percentage of Participants With Grade 3 or 4 AE at Week 48 | Up to 48 weeks | 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). |
| Percentage of Participants With Grade 3 or 4 AE at Week 96 | Up to 96 weeks | 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). |
| Percentage of Participants With Events of Death at Week 48 | Up to 48 weeks | The percentage of participants with events of death at Week 48 will be reported. |
| Percentage of Participants With Events of Death at Week 96 | Up to 96 weeks | The percentage of participants with events of death at Week 96 will be reported. |
| Percentage of Participants Discontinuing From Study Intervention Due to AE at Week 48 | Up to 48 weeks | 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. |
| Percentage of Participants Discontinuing from Study Intervention Due to AE at Week 96 | Up to 96 weeks | 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. |
| Percentage of Participants Discontinuing From Study Intervention Due to Drug-Related AE at Week 48 | Up to 48 weeks | 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. |
| Percentage of Participants Discontinuing From Study Intervention Due to Drug-Related AE at Week 96 | Up to 96 weeks | 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. |
| Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL at Week 24 | Up to 24 weeks | 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. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48 | Up to 48 weeks | 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. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | Up to 96 weeks | 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. |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 24 | Up to 24 weeks | 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. |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48 | Up to 48 weeks | 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. |
| Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96 | Up to 96 weeks | 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. |
| Percentage of Participants With HIV-1 RNA ≥50 copies/mL at Week 24 | Up to 24 weeks | 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. |
| Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 | Up to 48 weeks | 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. |
| Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96 | Up to 96 weeks | 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. |
| Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 24 | Baseline (Day 1) and 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. |
| Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 48 | Baseline (Day 1) and 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. |
| Percentage of Participants With Log10 Drop in Plasma HIV-1 RNA From Baseline at Week 96 | Baseline (Day 1) and 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. |
| Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 24 | Baseline (Day 1) and Week 24 | CD4+ T-cell counts will be performed at the central laboratory. |
| Change From Baseline in CD4+ T-Cell Counts at Week 48 | Baseline (Day 1) and Week 48 | CD4+ T-cell counts will be performed at the central laboratory. |
| Change From Baseline in CD4+ T-Cell Counts at Week 96 | Baseline (Day 1) and Week 96 | CD4+ T-cell counts will be performed at the central laboratory. |
| Viral Resistance-Associated Substitutions (RASs) to DOR or Other Treatment Components | Up to 96 weeks | The presence of viral RASs to DOR or other treatment components will be monitored for up to 96 weeks. |
| Percentage of Participants Adhering to DOR or to the FDC of DOR/3TC/TDF | Up to 96 weeks | Adherence to DOR or to the FDC of DOR/3TC/TDF will be monitored for up to 96 weeks. |
| Assessment of Palatability/Acceptability of Oral Pellets/Granules of DOR or the FDC of DOR/3TC/TDF | Day 28 | 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. |
Countries
Colombia, Mexico, Russia, South Africa, Thailand, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed