Dose Ranging, Switch Study of Islatravir (ISL) and MK-8507 Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013]
|
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: NCT04564547 |
|
Recruitment Status :
Active, not recruiting
First Posted : September 25, 2020
Last Update Posted : December 10, 2021
|
Sponsor:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief Summary:
This is a randomized, controlled, double-blind, dose-ranging study evaluating a switch to islatravir (ISL) and MK-8507 once-weekly in adult participants with human immunodeficiency virus type 1 (HIV-1) who have been virologically suppressed for ≥6 months on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily. The primary objectives are to evaluate the antiretroviral activity, safety, and tolerability of ISL with different doses of MK-8507 compared to continued BIC/FTC/TAF treatment.
Part 1 of the study is double-blind and at least 48 weeks in duration. Part 2 will commence once the dose is confirmed based on data through Week 48 from all participants in Part 1. In Parts 2 and 3, participants receive open-label treatment through Week 144.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV-1 Infection | Drug: Islatravir Drug: MK-8507 Drug: BIC/FTC/TAF Drug: Placebo to ISL Drug: Placebo to MK-8507 Drug: Placebo to BIC/FTC/TAF | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 161 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2b, Randomized, Active-Controlled, Double-Blind, Dose-Ranging Clinical Study to Evaluate a Switch to Islatravir (ISL) and MK-8507 Once-Weekly in Adults With HIV-1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) Once-Daily |
| Actual Study Start Date : | March 9, 2021 |
| Estimated Primary Completion Date : | June 24, 2022 |
| Estimated Study Completion Date : | June 6, 2024 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Group 1: ISL 20 mg + MK-8507 100 mg
Participants receive ISL 20 mg (Parts 1-3) + MK-8507 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD) [Part 1].
|
Drug: Islatravir
ISL capsule taken by mouth.
Other Name: MK-8591 Drug: MK-8507 MK-8507 tablet taken by mouth. Drug: Placebo to MK-8507 Placebo tablet matched to MK-8507 taken by mouth. Drug: Placebo to BIC/FTC/TAF Placebo tablet matched to BIC/FTC/TAF taken by mouth. |
|
Experimental: Group 2: ISL 20 mg + MK-8507 200 mg
Participants receive ISL 20 mg (Parts 1-3) + MK-8507 200 mg QW and placebo to BIC/FTC/TAF QD (Part 1).
|
Drug: Islatravir
ISL capsule taken by mouth.
Other Name: MK-8591 Drug: MK-8507 MK-8507 tablet taken by mouth. Drug: Placebo to MK-8507 Placebo tablet matched to MK-8507 taken by mouth. Drug: Placebo to BIC/FTC/TAF Placebo tablet matched to BIC/FTC/TAF taken by mouth. |
|
Experimental: Group 3: ISL 20 mg + MK-8507 400 mg
Participants receive ISL 20 mg (Parts 1-3) + MK-8507 400 mg QW and placebo to BIC/FTC/TAF QD (Part 1).
|
Drug: Islatravir
ISL capsule taken by mouth.
Other Name: MK-8591 Drug: MK-8507 MK-8507 tablet taken by mouth. Drug: Placebo to BIC/FTC/TAF Placebo tablet matched to BIC/FTC/TAF taken by mouth. |
|
Active Comparator: Group 4: BIC/FTC/TAF
Participants receive placebo to ISL + placebo to MK-8507 QW (Part 1) and BIC/FTC/TAF 50 mg/200 mg/25 mg QD (Parts 1 and 2).
|
Drug: BIC/FTC/TAF
BIC/FTC/TAF tablet taken by mouth.
Other Name: BIKTARVY® Drug: Placebo to ISL Placebo capsule matched to ISL taken by mouth. Drug: Placebo to MK-8507 Placebo tablet matched to MK-8507 taken by mouth. |
Primary Outcome Measures :
- Percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL [ Time Frame: Week 48 ]Plasma HIV-1 RNA levels will be determined with real time polymerase chain reaction (PCR) assay with a lower limit of quantification (LLoQ) of 40 copies/mL.
- Percentage of participants with ≥1 adverse event (AE) [ Time Frame: Up to 96 weeks ]The percentage of participants with AEs will be determined.
- Percentage of participants discontinuing study intervention due to AE [ Time Frame: Up to 96 weeks ]The percentage of participants discontinuing due to AEs will be determined.
Secondary Outcome Measures :
- Percentage of participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 48 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <40 copies/mL [ Time Frame: Week 48 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Percentage of participants with HIV-1 RNA ≥50 copies/mL [ Time Frame: Week 24 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 24 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <40 copies/mL [ Time Frame: Week 24 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Percentage of participants with HIV-1 RNA ≥50 copies/mL [ Time Frame: Week 96 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 96 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Percentage of participants with HIV-1 RNA <40 copies/mL [ Time Frame: Week 96 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Change from baseline (BL) in cluster of differentiation 4+ (CD4+) T-cell count [ Time Frame: Day 1 (BL) and Week 24 ]CD4+ T-cell counts will be determined at the central laboratory.
- Change from BL in CD4+ T-cell count [ Time Frame: Day 1 (BL) and Week 48 ]CD4+ T-cell counts will be determined at the central laboratory.
- Change from BL in CD4+ T-cell count [ Time Frame: Day 1 (BL) and Week 96 ]CD4+ T-cell counts will be determined at the central laboratory.
- Percentage of participants with HIV-1 RNA ≥50 copies/mL [ Time Frame: Week 144 ]Plasma HIV-1 RNA levels will be determined with real time PCR assay with a LLoQ of 40 copies/mL.
- Change from BL in CD4+ T-cell count [ Time Frame: Day 1 (BL) and Week 144 ]CD4+ T-cell counts will be determined at the central laboratory.
- Incidence of viral drug resistance [ Time Frame: Up to 144 weeks ]Participants with HIV-1 RNA >200 copies/mL will be assessed for development of viral drug resistance. Genotypic and phenotypic resistance will be determined with the commercially available GenoSure PRIme® and PhenoSense® assays, respectively.
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.
| 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 with plasma HIV-1 RNA <50 copies/mL at screening
- Has been virologically suppressed on BIC/FTC/TAF for ≥6 months
- Has a screening CD4+ T-cell count >200 cells/mm^3 (completed by the central laboratory)
- Is male or female, at least 18 years of age, at the time of signing the informed consent
- female participant 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 a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis)
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 active hepatitis C virus (HCV) coinfection (defined as detectable HCV RNA) or hepatitis B virus (HBV) coinfection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive)
- Has a current (active) diagnosis of acute hepatitis due to any cause
- 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
- Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
- 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 virological resistance to MK-8507 or nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI)
- Is female and 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): NCT04564547
Locations
Show 23 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: | NCT04564547 |
| Other Study ID Numbers: |
8591-013 2020-003071-18 ( EudraCT Number ) MK-8591-013 ( Other Identifier: Merck Protocol Number ) |
| First Posted: | September 25, 2020 Key Record Dates |
| Last Update Posted: | December 10, 2021 |
| Last Verified: | December 2021 |
| 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:
|
Islatravir Antiviral Agents Anti-Infective Agents Enzyme Inhibitors |
Molecular Mechanisms of Pharmacological Action Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Anti-Retroviral Agents |