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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03272347
Recruitment Status : Active, not recruiting
First Posted : September 5, 2017
Last Update Posted : March 20, 2020
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 islatravir (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: Islatravir Drug: Placebo to Islatravir Drug: Doravirine Drug: Placebo to Doravirine Drug: Lamivudine Drug: Placebo to Lamivudine Drug: MK-1439A Drug: Placebo to MK-1439A Drug: MK-8591A Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 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 Parts 3 and 4.
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 7, 2021
Estimated Study Completion Date : March 9, 2022

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: Islatravir 0.25 mg
Participants will be treated once daily (QD) with 0.25 mg islatravir, 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 islatravir and DOR 100 mg QD and continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.
Drug: Islatravir
Islatravir 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 open label dose may be administered.
Other Name: MK-8591

Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 144 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

Drug: MK-8591A
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks

Experimental: Islatravir 0.75 mg
Participants will be treated QD with 0.75 mg islatravir, 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 islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.
Drug: Islatravir
Islatravir 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 open label dose may be administered.
Other Name: MK-8591

Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 144 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

Drug: MK-8591A
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks

Experimental: Islatravir 2.25 mg
Participants will be treated QD with 2.25 mg islatravir, 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 islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.
Drug: Islatravir
Islatravir 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 open label dose may be administered.
Other Name: MK-8591

Drug: Doravirine
Doravirine 100 mg is orally administered QD in tablet form for up to 144 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

Drug: MK-8591A
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks

Active Comparator: MK-1439A
Participants will be treated QD with placebo to islatravir, 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 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192.
Drug: Placebo to Islatravir
Placebo to islatravir 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 144 weeks.

Drug: MK-8591A
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 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) up to Week 150 [ Time Frame: Up to Week 150 ]
    Number of participants experiencing AEs up to Week 150

  4. Discontinuations up to Week 144 [ Time Frame: Up to Week 144 ]
    Number of participants discontinuing study drug due to AEs up to Week 144


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. 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

  3. HIV-1 RNA up to Week 192 [ Time Frame: Up to Week 192 ]
    Percentage of participants with HIV-1 RNA <50 copies/mL up to 48 weeks after starting open-label doravirine/islatravir regimen

  4. 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

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

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

  7. CD4+ T-cell count at Week 144 [ Time Frame: Baseline and Week 144 ]
    Change from baseline in CD4+ T-cell count at Week 144

  8. CD4+ T-cell count at Week 192 [ Time Frame: Baseline and Week 192 ]
    Change from baseline in CD4+ T-cell count at Week 192

  9. Adverse Events (AEs) up to Week 48 [ Time Frame: Up to Week 48 ]
    Number of participants experiencing AEs 24 weeks after switching to Part 2 (up to 48 weeks)

  10. Discontinuations up to Week 48 [ Time Frame: Up to Week 48 ]
    Number of participants discontinuing study drug due to AEs 24 weeks after switching to Part 2 (up to 48 weeks)

  11. Adverse Events (AEs) from Week 96 up to Week 144 [ Time Frame: Week 96 up to Week 144 ]
    Number of participants experiencing AEs from Week 96 up to Week 144

  12. Discontinuations from Week 96 up to Week 144 [ Time Frame: Week 96 up to Week 144 ]
    Number of participants discontinuing study drug due to AEs from Week 96 up to Week 144

  13. AEs after Week 144 up to Week 192 [ Time Frame: Week 144 up to Week 192 ]
    Number of participants experiencing AEs during open label doravirine/islatravir treatment after week 144 up to week 192

  14. Discontinuations after Week 144 up to Week 192 [ Time Frame: Week 144 up to Week 192 ]
    Number of participants discontinuing study drug due to AEs during open label doravirine/islatravir treatment after week 144 up to week 192



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 islatravir (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
Show Show 26 study locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03272347    
Other Study ID Numbers: 8591-011
2017-000437-32 ( EudraCT Number )
First Posted: September 5, 2017    Key Record Dates
Last Update Posted: March 20, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lamivudine
4'-ethynyl-2-fluoro-2'-deoxyadenosine
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