Clinical trial NCT02629822: Safety and Efficacy of Doravirine, Tenofovir, Lamivudine (MK-1439A) in Participants Infected With Treatment-Naïve Human Immunodeficiency Virus (HIV) -1 With Transmitted Resistance (MK-1439A-030)
Official title: A Phase IIa Multicenter, Open-Label Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A in Treatment-Naïve HIV-1 Infected Subjects With Selected Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Transmitted Resistance Mutations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-12-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to evaluate the antiretroviral activity and the safety/tolerability of open-label doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF; MK-1439A; DELSTRIGO™) consisting of a single fixed-dose combination (FDC) tablet of DOR/3TC/TDF 100 mg/300 mg/300 mg in treatment-naïve HIV-1 infected participants with select non-nucleoside reverse transcriptase inhibitor (NNRTI) transmitted resistance-associated mutations.

Detailed description: This study had a Base Study (Day 1 to Week 96) and an optional Study Extension (Week 96 to Week 192).

Eligibility criteria: Inclusion Criteria:

* Is HIV-1 positive within 45 days prior to the treatment phase of this study, and have HIV treatment indicated based on physician assessment.
* Is naïve to antiretroviral therapy (ART) including investigational antiretroviral agents.
* Prior to screening, have had a genotype performed confirming the presence of only one of the following NNRTI mutations: K103N, Y181C, or G190A.
* Is considered clinically stable with no signs or symptoms of active infection at time of entry into the study (i.e. clinical status and all chronic medications should be unchanged for at least 2 weeks prior to the start of treatment in this study).
* Is highly unlikely to become pregnant or to impregnate a partner

Exclusion Criteria:

* Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence.
* Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1, including, but not limited to, adefovir, tenofovir, entecavir, emtricitabine, or lamivudine.
* Has documented or known resistance to study drugs (doravirine, lamivudine, and/or tenofovir)
* Has participated or anticipates participating in a study with an investigational compound/device within 30 days prior to signing informed consent
* Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial.
* Requires or anticipates requiring any of the prohibited medications
* Has significant hypersensitivity or other contraindication to any of the components of the study drug
* Has a current (active) diagnosis of acute hepatitis due to any cause
* Has evidence of decompensated liver disease or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score \> 9
* Is pregnant, breastfeeding, or expecting to conceive
* Is female and expecting to donate eggs, or is male and is expecting to donate sperm at any time during the study

Primary outcomes:
measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48
timeFrame: Week 48
measure: Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 48
timeFrame: Up to Week 48
measure: Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 48.
timeFrame: Up to Week 48
measure: Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 96
timeFrame: Up to Week 96
measure: Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 96
timeFrame: Up to Week 96
Secondary outcomes:
measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 96
timeFrame: Week 96
measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 48
timeFrame: Week 48
measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 96
timeFrame: Week 96
measure: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in CD4 Cell Count at Week 96
timeFrame: Baseline (Day 1) and Week 96
measure: Time to Loss of Virologic Response
timeFrame: Up to Week 96
Other outcomes:
measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 192
timeFrame: Week 192
measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 192
timeFrame: Week 192
measure: Change From Baseline in CD4 Cell Count at Week 192
timeFrame: Baseline (Day 1) and Week 192
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Wong A, Goldstein D, Mallolas J, DeJesus E, Johnson M, Molina JM, Pozniak A, Rodgers A, Teal V, Hepler D, Kumar S, Sklar P, Hanna GJ, Hwang C, Badshah C, Teppler H. Efficacy and Safety of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) in Treatment-Naive Adults With HIV-1 and Transmitted Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations. J Acquir Immune Defic Syndr. 2019 Dec 1;82(4):e47-e49. doi: 10.1097/QAI.0000000000002153.