Phase I/II Study of the Pharmacokinetics, Safety and Tolerability of Doravirine (MK-1439) and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (MK-1439A) in HIV-1-infected Children and Adolescents
- Conditions
- HIV-1 infectionMedDRA version: 20.1Level: PTClassification code 10020161Term: HIV infectionSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2017-001518-27-Outside-EU/EEA
- Lead Sponsor
- IAID, NICHD, NIMH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- Not specified
• 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
• 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method