Randomized, Double-blind, Efficacy, and Safety Study of Doravirine/Islatravir (DOR/ISL) in Treatment-naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020)
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| ClinicalTrials.gov Identifier: NCT04233879 |
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Recruitment Status :
Recruiting
First Posted : January 18, 2020
Last Update Posted : December 24, 2020
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Sponsor:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
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Brief Summary:
This is a phase 3, randomized, controlled, double-blind clinical study of a once-daily fixed dose combination (FDC) of 100 mg doravirine/0.75 mg islatravir (DOR/ISL [also known as MK-8591A]) in treatment-naïve participants with human immunodeficiency virus type-1 (HIV-1) infection. The primary hypothesis is that DOR/ISL is non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) treatment based on the percentage of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV-1 Infection | Drug: DOR/ISL Drug: BIC/FTC/TAF Drug: Placebo to BIC/FTC/TAF Drug: Placebo to DOR/ISL | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 680 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3 Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir Once-Daily in HIV-1 Infected Treatment-Naïve Participants |
| Actual Study Start Date : | February 28, 2020 |
| Estimated Primary Completion Date : | March 8, 2024 |
| Estimated Study Completion Date : | March 8, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group 1: DOR/ISL
Treatment-naïve participants with HIV-1 receive DOR/ISL and placebo to BIC/FTC/TAF once daily (QD) for 96 weeks.
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Drug: DOR/ISL
100 mg DOR/0.75 mg ISL FDC tablet taken once daily by mouth.
Other Names:
Drug: Placebo to BIC/FTC/TAF Placebo tablet matched to BIC/FTC/TAF taken by mouth. |
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Active Comparator: Group 2: BIC/FTC/TAF
Treatment-naïve participants with HIV-1 receive BIC/FTC/TAF and placebo to DOR/ISL QD for 96 weeks.
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Drug: BIC/FTC/TAF
BIC/FTC/TAF 50/200/25 mg FDC tablet taken once daily by mouth.
Other Name: Bictegravir/emtricitabine/tenofovir alafenamide Drug: Placebo to DOR/ISL Placebo tablet matched to DOR/ISL taken by mouth. |
Primary Outcome Measures :
- Percentage of participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 48 ]The percentage of participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay with a lower limit of detection (LLOD) of 40 copies/mL.
- Percentage of participants experiencing ≥1 adverse events (AEs) [ Time Frame: Up to 98 weeks ]An AE is 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 interventions.
- Percentage of participants discontinuing from study treatment due to AE(s) [ Time Frame: Up to 96 weeks ]An AE is 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 interventions.
Secondary Outcome Measures :
- Percentage of participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 96 ]The percentage of participants with HIV-1 RNA <50 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <40 copies/mL [ Time Frame: Week 48 ]The percentage of participants with HIV-1 RNA <40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <200 copies/mL [ Time Frame: Week 48 ]The percentage of participants with HIV-1 RNA <200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <40 copies/mL [ Time Frame: Week 96 ]The percentage of participants with HIV-1 RNA <40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <200 copies/mL [ Time Frame: Week 96 ]The percentage of participants with HIV-1 RNA <200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.
- Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts [ Time Frame: Day 1 (baseline) and Week 48 ]CD4+ T-cell counts will be measured by a central laboratory.
- Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts [ Time Frame: Day 1 (baseline) and Week 96 ]CD4+ T-cell counts will be measured by a central laboratory.
- Incidence of viral resistance-associated substitutions (RASs) [ Time Frame: Week 48 ]The incidence of viral RASs will be determined.
- Incidence of viral RASs [ Time Frame: Week 96 ]The incidence of viral RASs will be determined.
- Change from baseline in body weight [ Time Frame: Day 1 (baseline) and Week 48 ]The change from baseline in participant body weight will be determined.
- Change from baseline in body weight [ Time Frame: Day 1 (baseline) and Week 96 ]The change from baseline in participant body weight will be determined.
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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
- Is naïve to antiretroviral therapy (ART) defined as having received ≤10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); 2) Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis); 3) 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; 4) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required
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 HBV infection (defined as hepatitis B surface antigen [HBsAg]-positive or hepatitis B virus deoxyribonucleic acid [HBV DNA]-positive)
- 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
- Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study
- Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapy from 45 days prior to Day 1 through the study intervention period
- 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 intervention period
- Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention
- Has exclusionary laboratory values within 45 days prior to Day 1
- Is female and is expecting 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): NCT04233879
Contacts
| Contact: Toll Free Number | 1-888-577-8839 | Trialsites@merck.com |
Locations
Show 33 study locations
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: | NCT04233879 |
| Other Study ID Numbers: |
8591A-020 MK-8591A-020 ( Other Identifier: Merck Protocol Number ) 2019-000590-23 ( EudraCT Number ) |
| First Posted: | January 18, 2020 Key Record Dates |
| Last Update Posted: | December 24, 2020 |
| Last Verified: | December 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 |
| 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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Infection Tenofovir Emtricitabine Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors |
Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents |