HIV-1 infection MedDRA version: 20.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Pifeltro
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DORAVIRINE
Current Sponsor code: MK-1439
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration n
Sponsors
NIAID, NICHD, NIMH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Weight greater than or equal 35 kg at entry • If not of legal age to provide independent informed consent: Parent or guardian was willing and able to provide written informed consent for study participation; in addition, when applicable per local Institutional Review Board / Ethics Committee (IRB/EC) policies and procedures, potential participant was willing and able to provide written informed assent for study participation. If of legal age to provide independent informed consent as determined by site Standard Operating Procedures (SOPs) and consistent with site IRB/EC policies and procedures: Potential participant was willing and able to provide written informed consent for study participation • Confirmed HIV-1-infection based on documented testing of two samples collected at different time points. • Antiretroviral therapy (ART) exposure, virologic suppression, and resistance requirements, as follows: Cohort 1 • ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records: • At entry, receiving combination ART with raltegravir (RAL) or dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs); AND • At entry, had not received non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitor (PIs), or cobicistat within the previous 30 days; AND • Virologic suppression, as documented in medical records and as defined by: • One or more HIV RNA polymerase chain reaction (PCR) result below the level of quantification (BLLQ) within 15 months prior to enrollment, AND • If any HIV RNA PCR tests had been done within 3 months prior to enrollment, all results were below the level of quantification, AND • HIV RNA PCR result less than 40 copies/mL at screening. Cohort 2 ART-naive • ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records: • At entry, received no antiretrovirals (ARVs) for treatment of HIV infection including investigational agents (prior receipt of ARVs for prevention of perinatal transmission was permitted); AND • Screening genotypic resistance test results indicated susceptibility to doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) (see the protocol for more information; result must be available prior to enrollment); AND • If available, as documented in medical records, any prior genotypic resistance test result indicated susceptibility to DOR, TDF, and 3TC. Cohort 2 ART-experienced • ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records: • No previous history of change in ARVs due to clinical or virologic failure, in the opinion of the site investigator or designee; AND • Virologic suppression, as documented in medical record and as defined by: • One or more HIV RNA PCR result BLLQ within 15 months prior to enrollment, AND • If any HIV RNA PCR tests had been done within 3 months prior to enrollment, all results were below the level of quantification, AND • HIV RNA PCR result less than 40 copies/mL at screening; AND • If available, as documented in medical records, any prior genotypic resistance test result indicated susceptibility to DOR, TDF, and 3TC. • Grade 2 or lower hemoglobin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, and lipase on specimens obtained at screening • For Cohort 2 only, grade 2 or lower creatinine, proteinuria, a
Exclusion criteria
Exclusion criteria: • Evidence of decompensated liver disease manifested by the presence of or a history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of advanced liver diseases. • For Cohort 2 only, detectable hepatitis C virus (HCV) by RNA PCR or current or planned treatment with direct antiviral agent for HCV. • Presence of any active AIDS-defining opportunistic infection • History of malignancy (ever), with the exception of localized malignancies such as squamous cell or basal cell carcinoma of the skin • Clinical evidence of pancreatitis, as determined by the clinician (at entry) • Use of nafcillin, dicloxacillin, or any of the prohibited medications, within 30 days prior to study entry • For females, currently breastfeeding an infant at entry • Enrolled in another clinical trial of an investigational agent, device, or vaccine • Unlikely to adhere to the study procedures or keep appointments, in the opinion of the site investigator or designee • Used, or anticipates using, chronic systemic immunosuppressive agents or systemic interferon (e.g., for treatment of HCV infection) within 30 days prior to study entry. • Diagnosed with current active tuberculosis and/or was currently being treated with a rifampicin-containing regimen • Individual had any other condition, that in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1. Pharmacokinetic (PK) Parameter: Single-dose Area-under-the-curve (AUC0-8) of Doravirine (DOR) (Cohort 1) 2. PK Parameter: Single-dose Maximum Concentration (Cmax) of DOR (Cohort 1) 3. PK Parameter: Single-dose 24 Hour-concentration (C24hr) of DOR (Cohort 1) 4. Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug 5. Percentage of Participants With Serious Adverse Events (SAEs) Assessed as Related to Study Drug 6. Percentage of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events Assessed as Related to Study Drug 7. Percentage of Participants With Grade 5 Adverse Events (Death) Regardless of Relationship to Study Drug ;Timepoint(s) of evaluation of this end point: 1., 2. and 3. Measured during the entry (day 0) visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12, 24, 48 and 72 hours post-dose. 4., 5. 6. and 7. Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24. ;Main Objective: Cohort 1: 1. Evaluate the pharmacokinetics of a single dose of DOR in HIV-1-infected children and adolescents, when added to a stable ART regimen comprised of an InSTI plus two NRTIs, using intensive PK sampling at Entry for identification of minimum weight threshold for doravirine 100 mg dose. 2. Evaluate the 2-week safety and tolerability of a single dose of DOR in HIV-1-infected children and adolescents, when added to a stable ART regimen comprised of an InSTI plus two NRTIs. Cohort 2: 1. Evaluate the 24-week safety and tolerability of DOR/3TC/TDF in HIV-1-infected children and adolescents. ;Secondary Objective: Cohort 2: 1. Evaluate the pharmacokinetics of DOR, 3TC, and tenofovir in HIV-1-infected children and adolescents receiving DOR/3TC/TDF, using intensive (tenofovir and 3TC) and semi-intensive (DOR) PK sampling at Week 1. 2. Evaluate the 24-, 48-, and 96-week virologic efficacy of DOR/3TC/TDF in HIV-1-infected chil | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PK Parameter: AUC0-24hr of DOR (Cohort 2) 2. PK Parameter: AUC0-24hr of 3TC (Cohort 2) 3. PK Parameter: AUC0-24hr of Tenofovir (Cohort 2) 4. PK Parameter: Cmax of DOR (Cohort 2) 5. PK Parameter: Cmax of 3TC (Cohort 2) 6. PK Parameter: Cmax of Tenofovir (Cohort 2) 7. PK Parameter: C24hr of DOR (Cohort 2) 8. PK Parameter: C24hr of 3TC (Cohort 2) 9. PK Parameter: C24hr of Tenofovir (Cohort 2) 10. Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 24 (Cohort 2) 11. Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 48 (Cohort 2) 12. Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 96 (Cohort 2) 13. Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 24 (Cohort 2) 14. Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 48 (Cohort 2) 15. Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 96 (Cohort 2) 16. Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 24 (Cohort 2) 17. Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 48 (Cohort 2) 18. Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 96 (Cohort 2) 19. Summary of log10 Drop From Baseline to Week 24 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2) 20. Summary of log10 Drop From Baseline to Week 48 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2) 21. Summary of log10 Drop From Baseline to Week 96 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2) 22. Summary of Changes in CD4 Count From Baseline to Week 24 (Cohort 2) 23. Summary of Changes in CD4 Count From Baseline to Week 48 (Cohort 2) 24. Summary of Changes in CD4 Count From Baseline to Week 96 (Cohort 2) 25. Summary of Changes in CD4 Percent From Baseline to Week 24 (Cohort 2) 26. Summary of Changes in CD4 Percent From Baseline to Week | — |
Countries
South Africa, Thailand, United States
Contacts
Public ContactHedy Teppler
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed