Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05631093




Registration number
NCT05631093
Ethics application status
Date submitted
18/11/2022
Date registered
30/11/2022
Date last updated
8/11/2024

Titles & IDs
Public title
A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051)
Scientific title
A Phase 3, Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy
Secondary ID [1] 0 0
MK-8591A-051
Secondary ID [2] 0 0
8591A-051
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV-1 Infection 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ART
Treatment: Drugs - DOR/ISL

Active comparator: ART + DOR/ISL - Participants with HIV-1 that has been virologically suppressed for =3 consecutive months on a stable oral ART are first treated with standard of care (SOC) ART for 48 weeks, followed by 96 weeks of treatment with DOR/ISL Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).

Experimental: DOR/ISL - Participants with HIV-1 that has been virologically suppressed for =3 consecutive months on a stable oral ART are treated with DOR/ISL for 144 weeks. Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).


Treatment: Drugs: ART
Standard of care ART, per approved product list, taken orally

Treatment: Drugs: DOR/ISL
Combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Participants with HIV-1 RNA =50 copies/mL at Week 48
Timepoint [1] 0 0
Week 48
Primary outcome [2] 0 0
Participants with one or more AEs at Week 48
Timepoint [2] 0 0
Up to Week 48
Primary outcome [3] 0 0
Participants with an AE leading to discontinuation of study intervention at Week 48
Timepoint [3] 0 0
Up to Week 48
Secondary outcome [1] 0 0
Participants with HIV-1 RNA <200 copies/mL at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Participants with HIV-1 RNA <50 copies/mL at Week 48
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Participants with HIV-1 RNA <200 copies/mL at Week 96
Timepoint [3] 0 0
Week 96
Secondary outcome [4] 0 0
Participants with HIV-1 RNA <200 copies/mL at Week 144
Timepoint [4] 0 0
Week 144
Secondary outcome [5] 0 0
Participants with HIV-1 RNA =50 copies/mL at Week 96
Timepoint [5] 0 0
Week 96
Secondary outcome [6] 0 0
Participants with HIV-1 RNA =50 copies/mL at Week 144
Timepoint [6] 0 0
Week 144
Secondary outcome [7] 0 0
Participants with HIV-1 RNA <50 copies/mL at Week 96
Timepoint [7] 0 0
Week 96
Secondary outcome [8] 0 0
Participants with HIV-1 RNA <50 copies/mL at Week 144
Timepoint [8] 0 0
Week 144
Secondary outcome [9] 0 0
Change from Day 1 in cluster of differentiation 4+ (CD4+) T-cell count at Week 48
Timepoint [9] 0 0
Baseline at Day 1 and Week 48
Secondary outcome [10] 0 0
Change from Week 48 in CD4+ T-cell count at Week 96
Timepoint [10] 0 0
Baseline at Week 48 and Week 96
Secondary outcome [11] 0 0
Change from Week 48 in CD4+ T-cell count at Week 144
Timepoint [11] 0 0
Baseline at Week 48 and Week 144
Secondary outcome [12] 0 0
Change from Day 1 in CD4+ T-cell count at Week 96
Timepoint [12] 0 0
Baseline at Day 1 and Week 96
Secondary outcome [13] 0 0
Change from Day 1 in CD4+ T-cell count at Week 144
Timepoint [13] 0 0
Baseline at Day 1 and Week 144
Secondary outcome [14] 0 0
Participants with viral resistance-associated substitutions
Timepoint [14] 0 0
Up to Week 144
Secondary outcome [15] 0 0
Low density lipoprotein cholesterol (LDL-C)
Timepoint [15] 0 0
Baseline and Week 48
Secondary outcome [16] 0 0
High density lipoprotein cholesterol (HDL-C)
Timepoint [16] 0 0
Baseline and Week 48
Secondary outcome [17] 0 0
Participants with one or more AEs at Week 96
Timepoint [17] 0 0
Up to Week 96
Secondary outcome [18] 0 0
Participants with one or more AEs at Week 144
Timepoint [18] 0 0
Up to Week 144
Secondary outcome [19] 0 0
Participants with AEs leading to discontinuation of study intervention at Week 96
Timepoint [19] 0 0
Up to Week 96
Secondary outcome [20] 0 0
Participants with AEs leading to discontinuation of study intervention at Week 144
Timepoint [20] 0 0
Up to Week 144
Secondary outcome [21] 0 0
Participants with one or more AEs from Week 48 up to Week 96
Timepoint [21] 0 0
Week 48 up to Week 96
Secondary outcome [22] 0 0
Participants with one or more AEs from Week 48 up to Week 144
Timepoint [22] 0 0
Week 48 up to Week 144
Secondary outcome [23] 0 0
Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 96
Timepoint [23] 0 0
Week 48 up to Week 96
Secondary outcome [24] 0 0
Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 144
Timepoint [24] 0 0
Week 48 up to Week 144

Eligibility
Key inclusion criteria
* Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening
* Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) ART with documented viral suppression (HIV-1 RNA <50 copies/mL) for =3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
* Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
* Has active hepatitis B virus (HBV) infection
* Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
* Has a =5 years prior history of malignancy
* Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A ) inducers
* Has taken long-acting HIV therapy at any time
* Is currently participating in or has participated in a clinical study and received (or is receiving) 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
11/07/2028
Actual
Sample size
Target
Accrual to date
Final
553
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Holdsworth House Medical Practice ( Site 4200) - Darlinghurst
Recruitment hospital [2] 0 0
St Vincent's Hospital-IBAC ( Site 4203) - Sydney
Recruitment hospital [3] 0 0
Holdsworth House Medical Practice - Brisbane ( Site 4201) - Brisbane
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 4204) - Brisbane
Recruitment hospital [5] 0 0
Prahran Market Clinic ( Site 4202) - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
4006 - Brisbane
Recruitment postcode(s) [4] 0 0
4029 - Brisbane
Recruitment postcode(s) [5] 0 0
3181 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Colombia
State/province [10] 0 0
Atlantico
Country [11] 0 0
Colombia
State/province [11] 0 0
Valle Del Cauca
Country [12] 0 0
Japan
State/province [12] 0 0
Aichi
Country [13] 0 0
Japan
State/province [13] 0 0
Tokyo
Country [14] 0 0
South Africa
State/province [14] 0 0
Free State
Country [15] 0 0
South Africa
State/province [15] 0 0
Gauteng
Country [16] 0 0
South Africa
State/province [16] 0 0
Kwazulu-Natal
Country [17] 0 0
South Africa
State/province [17] 0 0
Western Cape
Country [18] 0 0
Switzerland
State/province [18] 0 0
Basel-Stadt
Country [19] 0 0
Switzerland
State/province [19] 0 0
Geneve
Country [20] 0 0
Switzerland
State/province [20] 0 0
Ticino
Country [21] 0 0
Switzerland
State/province [21] 0 0
Vaud
Country [22] 0 0
Switzerland
State/province [22] 0 0
Zurich
Country [23] 0 0
Switzerland
State/province [23] 0 0
Berne
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Brighton And Hove
Country [25] 0 0
United Kingdom
State/province [25] 0 0
England
Country [26] 0 0
United Kingdom
State/province [26] 0 0
London, City Of
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) =50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.
Trial website
https://clinicaltrials.gov/study/NCT05631093
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05631093