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MK-8591 With Doravirine and Lamivudine in Participants Infected With Human Immunodeficiency Virus Type 1 (MK-8591-011) (DRIVE2Simplify)

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ClinicalTrials.gov Identifier: NCT03272347
Recruitment Status : Active, not recruiting
First Posted : September 5, 2017
Last Update Posted : April 26, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of MK-8591 in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection.

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: MK-8591 Drug: Placebo to MK-8591 Drug: Doravirine Drug: Placebo to Doravirine Drug: Lamivudine Drug: Placebo to Lamivudine Drug: MK-1439A Drug: Placebo to MK-1439A Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Masking in Part 1, including matching placebo. Masking only to dose in Part 2. No masking in Part 3.
Primary Purpose: Treatment
Official Title: A Phase 2B, Randomized, Double-Blind, Active-Comparator-Controlled, Dose-Ranging Clinical Trial to Evaluate the Safety, Tolerability, Antiretroviral Activity, and Pharmacokinetics of MK-8591 Given in Combination With Doravirine (DOR) and Lamivudine (3TC) in HIV-1-Infected Treatment-Naïve Adults
Actual Study Start Date : November 27, 2017
Estimated Primary Completion Date : April 9, 2019
Estimated Study Completion Date : September 29, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Lamivudine

Arm Intervention/treatment
Experimental: MK-8591 0.25 mg
Participants will be treated once daily (QD) with 0.25 mg MK-8591, 100 mg DOR, 300 mg 3TC, and placebo to MK- 1439A for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to MK-1439A may be discontinued. Around Week 60, participants may be switched to a selected open label dose of MK-8591 and DOR 100 mg QD and continue treatment until Week 120.
Drug: MK-8591
MK-8591 at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected dose may be administered.

Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 120 weeks
Other Name: MK-1439

Drug: Lamivudine
Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks
Other Name: 3TC

Drug: Placebo to MK-1439A
Placebo to MK-1439A is orally administered QD in tablet form for up to 52 weeks

Experimental: MK-8591 0.75 mg
Participants will be treated QD with 0.75 mg MK-8591, 100 mg DOR, 300 mg 3TC, and placebo to MK- 1439A for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to MK-1439A may be discontinued. Around Week 60, participants may be switched to a selected open label dose of MK-8591 and DOR 100 mg QD and will continue treatment until Week 120.
Drug: MK-8591
MK-8591 at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected dose may be administered.

Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 120 weeks
Other Name: MK-1439

Drug: Lamivudine
Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks
Other Name: 3TC

Drug: Placebo to MK-1439A
Placebo to MK-1439A is orally administered QD in tablet form for up to 52 weeks

Experimental: MK-8591 2.25 mg
Participants will be treated QD with 2.25 mg MK-8591, 100 mg DOR, 300 mg 3TC, and placebo to MK- 1439A for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to MK-1439A may be discontinued. Around Week 60, participants may be switched to a selected open label dose of MK-8591 and DOR 100 mg QD and will continue treatment until Week 120.
Drug: MK-8591
MK-8591 at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected dose may be administered.

Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 120 weeks
Other Name: MK-1439

Drug: Lamivudine
Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks
Other Name: 3TC

Drug: Placebo to MK-1439A
Placebo to MK-1439A is orally administered QD in tablet form for up to 52 weeks

Active Comparator: MK-1439A
Participants will be treated QD with placebo to MK-8591, placebo to DOR, placebo to 3TC, and MK-1439A consisting of 100 mg DOR + 300 mg 3TC + 300 mg tenofovir disoproxil fumarate (TDF) for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments may be discontinued and participants will receive only MK-1439A QD open label up to Week 120.
Drug: Placebo to MK-8591
Placebo to MK-8591 is orally administered QD in capsule form for up to 52 weeks

Drug: Placebo to Doravirine
Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks

Drug: Placebo to Lamivudine
Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks

Drug: MK-1439A
MK-1439A consisting of 100 mg Doravirine + 300 mg Lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 120 weeks.




Primary Outcome Measures :
  1. HIV-1 RNA at Week 24 [ Time Frame: Week 24 ]
    Percentage of participants with HIV-1 RNA <50 copies/mL at Week 24

  2. HIV-1 RNA at Week 48 [ Time Frame: Week 48 ]
    Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48

  3. Adverse Events (AEs) [ Time Frame: Up to Week 126 ]
    Number of participants experiencing AEs

  4. Discontinuations [ Time Frame: Up to Week 120 ]
    Number of participants discontinuing study drug due to AEs


Secondary Outcome Measures :
  1. HIV-1 RNA up to Week 72 [ Time Frame: Up to Week 72 ]
    Percentage of participants with HIV-1 RNA <50 copies/mL up to 48 weeks after 3TC and placebo are discontinued from the regimen

  2. CD4+ T-cell count at Week 24 [ Time Frame: Baseline and Week 24 ]
    Change from baseline in mature T-helper (CD4+ T)-cell count at Week 24

  3. CD4+ T-cell count at Week 48 [ Time Frame: Baseline and Week 48 ]
    Change from baseline in CD4+ T-cell count at Week 48

  4. CD4+ T-cell count at Week 96 [ Time Frame: Baseline and Week 96 ]
    Change from baseline in CD4+ T-cell count at Week 96

  5. HIV-1 RNA up to Week 96 [ Time Frame: Up to Week 96 ]
    Percentage of participants with HIV-1 RNA <50 copies/mL up to 72 weeks after 3TC and placebo are discontinued from the regimen



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has HIV-1 infection
  • Is naïve to anti-retroviral therapy (ART).
  • Is clinically stable, with no signs or symptoms of acute infection, at the time of entry into the study
  • Female is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP); but if WOCBP agrees to follow the contraceptive guidance
  • All participants, male and female, agree to use barrier methods of contraception when engaged in any sexual activity during treatment and for 6 weeks following treatment.

Exclusion Criteria:

  • Is a user of recreational or illicit drugs or has had a history of drug or alcohol abuse or dependence that may interfere with trial participation
  • Has significant hypersensitivity or other contraindication to any of the components of the study drugs
  • Has a history of malignancy ≤5 years prior
  • Female expects to donate eggs at any time during the study
  • Is breastfeeding or expecting to conceive
  • A WOCBP who has a positive urine pregnancy test on Day 1 before the first dose of study treatment
  • Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
  • Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
  • Requires any of the following prohibited medications: Carbamazepine, Phenobarbital, Phenytoin, Rifabutin, Rifampin, Herbal remedies, St. John's Wort, Modafinil, Bosentan, Nafcillin, Pentostatin
  • Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing informed consent to participate in this current trial
  • Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, protease inhibitor, integrase inhibitor
  • Has active hepatitis C virus (HCV) coinfection defined as detectable HCV RNA or HBV co-infection defined as hepatitis B surface antigen [HBsAg]-positive
  • Has a current (active) diagnosis of acute hepatitis due to any cause
  • Has previously been randomized in a study and received MK-8591, DOR, MK-1439A, or 3TC.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03272347


Locations
United States, Arizona
Pueblo Family Physicians ( Site 0119)
Phoenix, Arizona, United States, 85015
United States, California
University California / Davis ( Site 0101)
Sacramento, California, United States, 95817
United States, District of Columbia
Whitman Walker Clinic ( Site 0108)
Washington, District of Columbia, United States, 20005
United States, Florida
Orlando Immunology Center (OIC) ( Site 0105)
Orlando, Florida, United States, 32803
United States, Illinois
Northstar Medical Center ( Site 0102)
Chicago, Illinois, United States, 60657
United States, Missouri
Kansas City CARE Clinic ( Site 0106)
Kansas City, Missouri, United States, 64111
United States, Texas
Saint Hope Foundation, Inc. ( Site 0116)
Bellaire, Texas, United States, 77401
North Texas Infectious Diseases Consultants, PA ( Site 0103)
Dallas, Texas, United States, 75246
Tarrant County Infectious Disease Associates ( Site 0112)
Fort Worth, Texas, United States, 76104
The Crofoot Research Center, Inc. ( Site 0118)
Houston, Texas, United States, 77098
Chile
Clinica Arauco Salud ( Site 0200)
Santiago, RM, Chile
Biomedica Research Group ( Site 0202)
Santiago, Chile
Hospital Dr. Hernan Henriquez Aravena ( Site 0203)
Temuco, Chile
France
Hopital Avicenne ( Site 2302)
Bobigny, France
Hopital Saint-Andre ( Site 2307)
Bordeaux, France
CHU Hotel Dieu ( Site 2308)
Nantes, France
CHU de Nice Hopital Archet 1 ( Site 2303)
Nice, France
Hopital Bichat - Claude Bernard ( Site 2309)
Paris, France
Hopital Pitie Salpetriere ( Site 2305)
Paris, France
Hopital Saint Louis ( Site 2306)
Paris, France
Centre Hospitalier de Tourcoing ( Site 2301)
Tourcoing, France
United Kingdom
Brighton and Sussex University Hospitals NHS Trust ( Site 2105)
Brighton, East Sussex, United Kingdom
Chelsea and Westminster Hospital ( Site 2101)
London, United Kingdom
Royal London Hospital ( Site 2103)
London, United Kingdom
The Royal Free London NHS Foundation Trust ( Site 2102)
London, United Kingdom
North Manchester General Hospital ( Site 2104)
Manchester, United Kingdom
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03272347     History of Changes
Other Study ID Numbers: 8591-011
2017-000437-32 ( EudraCT Number )
First Posted: September 5, 2017    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lamivudine
Tenofovir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents