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)

NCT02629822 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 1439A-0302015-003616-20MK-1439A-030
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48

  The percentage of participants achieving HIV-1 ribonucleic acid (RNA) \<50 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit.

  Week 48

• Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 48

  The percentage of participants experiencing ≥1 AE up to Week 48 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

  Up to Week 48

• Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 48.

  The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

  Up to Week 48

• Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 96

  The percentage of participants experiencing ≥1 AE up to Week 96 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

  Up to Week 96

• Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 96

  The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

  Up to Week 96

Secondary Outcomes (6)

• Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 96

  Week 96

• Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 48

  Week 48

• Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 96

  Week 96

• Change From Baseline in CD4 Cell Count at Week 48

  Baseline (Day 1) and Week 48

• Change From Baseline in CD4 Cell Count at Week 96

  Baseline (Day 1) and Week 96

Other Outcomes (3)

• Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 192

  Week 192

• Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 192

  Week 192

• Change From Baseline in CD4 Cell Count at Week 192

  Baseline (Day 1) and Week 192

Study Arms (1)

DOR/3TC/TDF

EXPERIMENTAL

Treatment-naïve HIV-1 infected participants with NNRTI transmitted resistance-associated mutations were treated with open-label MK-1439A (DOR/3TC/TDF 100mg/300mg/300mg) as a FDC tablet taken once daily by mouth for 96 weeks in the Base Study. In addition, eligible participants continued to receive the same MK-1439A regimen from Week 96 to Week 192 during the Extension Study.

Drug: Doravirine/lamivudine/tenofovir disoproxil fumarate

Interventions

Doravirine/lamivudine/tenofovir disoproxil fumarate DRUG

FDC tablet containing MK-1439 (doravirine) 100 mg / lamivudine 300 mg / tenofovir disoproxil fumarate 300 mg taken by mouth.

Also known as: MK-1439A, DELSTRIGO™

DOR/3TC/TDF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 31425317 RESULT

MeSH Terms

Interventions

doravirine

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2015
• First Posted: December 14, 2015
• Study Start: January 14, 2016
• Primary Completion: November 28, 2018
• Study Completion: October 28, 2020
• Last Updated: October 26, 2021
• Results First Posted: December 26, 2019

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share