Evaluating the Pharmacokinetics, Safety, and Tolerability of Doravirine (MK-1439) and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (MK-1439A) in HIV-1-Infected Children and Adolescents

Completed · Phase 1/Phase 2

Conditions studied: HIV Infections

In brief

The purpose of this study was to evaluate the pharmacokinetics, safety, and tolerability of doravirine (also called MK-1439 or DOR) and doravirine/lamivudine/tenofovir disoproxil fumarate (also called MK-1439A or DOR/3TC/TDF) in HIV-1-infected children and adolescents.

Key facts

Study ID

NCT03332095

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

55

Starts

2018-07-02

Expected to finish

2022-05-25

Last updated by the study team

2023-02-14

Who can join

Age: 12 and older, up to 17. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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. More information on this criterion can be found in the protocol.
• 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, performed as per the protocol.
• 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), performed as per the protocol; AND
• If available, as documented in medical records, any prior genotypic resistance test result indicated susceptibility to DOR, TDF, and 3TC (see the protocol for more information).
• Note: For individuals that were re-screened, the genotypic resistance test did not need to be repeated.
• 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 (see the protocol for more information); AND

You may not qualify if…

• 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.
• Note: Individuals with chronic hepatitis B who had grade 2 or lower ALT and AST and had no significant impairment of hepatic synthetic function (significant impairment of hepatic synthetic function was defined as a serum albumin less than 2.8 mg/dL or an international normalized ratio (INR) greater than 1.7 in the absence of another explanation for the abnormal laboratory value) were eligible.
• For Cohort 2 only, detectable hepatitis C virus (HCV) by RNA PCR or current or planned treatment with direct antiviral agent for HCV.
• Note: HCV antibody positivity but undetectable by HCV RNA PCR results were permitted.
• 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 (see the protocol for a complete list of prohibited medications)
• 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.
• Note: Systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg/day) for replacement therapy or short courses (less than or equal to 30 days) were permitted. See the protocol for a complete list of prohibited medications.
• 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

Where it is running

• Univ. of Colorado Denver NICHD CRS — Aurora, Colorado, United States
• Boston Medical Center Ped. HIV Program NICHD CRS — Boston, Massachusetts, United States
• St. Jude Children's Research Hospital CRS — Memphis, Tennessee, United States
• Seattle Children's Research Institute CRS — Seattle, Washington, United States
• Soweto IMPAACT CRS — Johannesburg, Gauteng, South Africa
• Siriraj Hospital ,Mahidol University NICHD CRS — Bangkok, Bangkoknoi, Thailand
• Chiangrai Prachanukroh Hospital NICHD CRS — Chiang Mai, Thailand
• Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS — Chiang Mai, Thailand

Full record on ClinicalTrials.gov

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