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Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017)

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: NCT04223778
Recruitment Status : Active, not recruiting
First Posted : January 10, 2020
Results First Posted : September 19, 2022
Last Update Posted : November 29, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:
This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified background antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.

Condition or disease Intervention/treatment Phase
HIV Infection Drug: DOR/ISL Drug: ART Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 672 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy
Actual Study Start Date : February 18, 2020
Actual Primary Completion Date : September 8, 2021
Estimated Study Completion Date : March 30, 2024

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: Doravirine/Islatravir (DOR/ISL)
Participants who were previously treated with continuous background antiretroviral therapy (ART) will receive DOR/ISL, a fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) orally once daily for 96 weeks.
Drug: DOR/ISL
A FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily
Other Name: MK-8591A

Active Comparator: Baseline Background Antiretroviral Therapy (ART)
Participants will receive continuous background ART for 48 weeks and DOR/ISL, a FDC of 100 mg DOR/0.75 mg ISL orally once daily for 48 weeks.
Drug: DOR/ISL
A FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily
Other Name: MK-8591A

Drug: ART
Baseline background ART regimen will be administered as per approved label. ART medication will not be provided by the Sponsor; participants will provide their own ART medications. Allowed drug classes include nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transferase inhibitors (InSTIs), fusion inhibitors, chemokine receptor 5 (CCR5) antagonists, post-attachment inhibitor, and pharmacokinetic (PK) boosters.




Primary Outcome Measures :
  1. Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48 [ Time Frame: Week 48 ]
    HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

  2. Percentage of Participants With One or More Adverse Events (AEs) up to Week 48 [ Time Frame: Up to ~48 Weeks ]
    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least one AE was reported.

  3. Percentage of Participants Who Discontinued Study Intervention up to Week 48 [ Time Frame: Up to ~48 Weeks ]
    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE was reported.


Secondary Outcome Measures :
  1. Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48 [ Time Frame: Week 48 ]
    HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA <40 copies/mL or <50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

  2. Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL From Week 48 to Week 96 [ Time Frame: Weeks 48-96 (up to ~48 weeks) ]
    HIV-1 RNA levels in blood samples taken at each visit will be measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL from Week 48 to Week 96 will be presented using the FDA Snapshot missing data approach.

  3. Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96 [ Time Frame: Week 96 ]
    HIV-1 RNA levels in blood samples taken at each visit will be measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 will be presented using the FDA Snapshot missing data approach.

  4. Percentage Change From Baseline in CD4+ T-cell Count at Week 48 [ Time Frame: Baseline and Week 48 ]
    Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The percentage change from baseline to Week 48 is presented.

  5. Percentage Change From Baseline in CD4+ T-cell Count at Week 96 [ Time Frame: Baseline and Week 96 ]
    Plasma CD4+ T-Cell Count will be measured in cells/mm^3 for baseline and 96 weeks. Baseline measurements will be defined as the Day 1 value of each participant. The percentage change from baseline to Week 96 will be presented.

  6. Percentage Change From Week 48 in CD4+ T-cell Count at Week 96 [ Time Frame: Week 48 and Week 96 ]
    Plasma CD4+ T-Cell Count will be measured in cells/mm^3 for Week 48 and Week 96. The percentage change from Week 48 to Week 96 will be presented.

  7. Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48 [ Time Frame: Week 48 ]
    Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated drug resistance at Week 48 is presented.

  8. Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96 [ Time Frame: Week 96 ]
    Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrate drug resistance at Week 96 will be presented.

  9. Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) [ Time Frame: Baseline and Week 24 ]
    Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.

  10. Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) [ Time Frame: Baseline and Week 24 ]
    Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.

  11. Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens [ Time Frame: Baseline and Week 24 ]
    Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.

  12. Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens) [ Time Frame: Baseline and Week 48 ]
    Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.

  13. Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens) [ Time Frame: Baseline and Week 48 ]
    Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.

  14. Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens [ Time Frame: Baseline and Week 48 ]
    Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.

  15. Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens) [ Time Frame: Baseline and Week 48 ]
    Baseline measurements were defined as the Day 1 value of each participant. The change from baseline to Week 48 is presented for participants who received InSTI- based regimens.

  16. Percentage of Participants With One or More AEs up to Week 96 [ Time Frame: Up to ~96 Weeks ]
    An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.

  17. Percentage of Participants Who Discontinued Study Intervention up to Week 96 [ Time Frame: Up to ~96 Weeks ]
    An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study intervention due to an AE will be reported.

  18. Percentage of Participants With One or More AEs From Week 48 to Week 96 [ Time Frame: Weeks 48-96 ]
    An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.

  19. Percentage of Participants Who Discontinued Study Intervention From Week 48 to Week 96 [ Time Frame: Weeks 48-96 ]
    An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study intervention due to an AE will be reported.



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:

  • Is HIV-1 positive
  • Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
  • Female is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive

Exclusion Criteria:

  • Has HIV-2 infection
  • Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
  • Has an active diagnosis of hepatitis due to any cause, including active Hepatitis B Virus (HBV) co-infection
  • Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
  • Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
  • Is currently taking long-acting cabotegravir-rilpivirine
  • Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period
  • Has a documented or known virologic resistance to DOR
  • Female expects to conceive or donate eggs at any time during the study

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): NCT04223778


Locations
Show Show 78 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT04223778    
Other Study ID Numbers: 8591A-017
MK-8591A-017 ( Other Identifier: Merck )
205165 ( Registry Identifier: JAPIC-CTI )
2019-000586-20 ( EudraCT Number )
First Posted: January 10, 2020    Key Record Dates
Results First Posted: September 19, 2022
Last Update Posted: November 29, 2022
Last Verified: November 2022
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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HIV Infections
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Islatravir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents