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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05630755




Registration number
NCT05630755
Ethics application status
Date submitted
18/11/2022
Date registered
30/11/2022
Date last updated
7/11/2024

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 Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052)
Scientific title
A Phase 3, Randomized, Active-Controlled, Double-Blind 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 Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
Secondary ID [1] 0 0
MK-8591A-052
Secondary ID [2] 0 0
8591A-052
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 - DOR/ISL
Treatment: Drugs - BIC/FTC/TAF
Treatment: Drugs - Placebo to BIC/FTC/TAF
Treatment: Drugs - Placebo to DOR/ISL

Experimental: DOR/ISL and Placebo to BIC/FTC/TAF - Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).

Active comparator: BIC/FTC/TAF and Placebo to DOR/ISL - Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).


Treatment: Drugs: DOR/ISL
DOR/ISL 100 mg/0.25 mg oral tablets once daily

Treatment: Drugs: BIC/FTC/TAF
BIC/FTC/TAF 50 mg/200 mg/25 mg oral tablets once daily

Treatment: Drugs: Placebo to BIC/FTC/TAF
0 mg oral tablets once daily

Treatment: Drugs: Placebo to DOR/ISL
0 mg oral tablets once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants with HIV-1 RNA =50 copies/mL at Week 48
Timepoint [1] 0 0
Week 48
Primary outcome [2] 0 0
Percentage of participants who experience adverse events (AEs) through Week 48
Timepoint [2] 0 0
Up to Week 48
Primary outcome [3] 0 0
Percentage of participants who discontinue study intervention due to AEs through Week 48
Timepoint [3] 0 0
Up to Week 48
Secondary outcome [1] 0 0
Percentage of participants with HIV-1 RNA =50 copies/mL at Week 96
Timepoint [1] 0 0
Week 96
Secondary outcome [2] 0 0
Percentage of participants with HIV-1 RNA =50 copies/mL at Week 144
Timepoint [2] 0 0
Week 144
Secondary outcome [3] 0 0
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48
Timepoint [3] 0 0
Week 48
Secondary outcome [4] 0 0
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96
Timepoint [5] 0 0
Week 96
Secondary outcome [6] 0 0
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96
Timepoint [6] 0 0
Week 96
Secondary outcome [7] 0 0
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144
Timepoint [7] 0 0
Week 144
Secondary outcome [8] 0 0
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144
Timepoint [8] 0 0
Week 144
Secondary outcome [9] 0 0
Change from baseline in 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 baseline in CD4+ T-cell count at Week 96
Timepoint [10] 0 0
Baseline at Day 1 and Week 96
Secondary outcome [11] 0 0
Change from baseline in CD4+ T-cell count at Week 144
Timepoint [11] 0 0
Baseline at Day 1 and Week 144
Secondary outcome [12] 0 0
Number of participants with viral drug resistance mutations at Week 48
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
Number of participants with viral drug resistance mutations at Week 96
Timepoint [13] 0 0
Week 96
Secondary outcome [14] 0 0
Number of participants with viral drug resistance mutations at Week 144
Timepoint [14] 0 0
Week 144
Secondary outcome [15] 0 0
Percentage of participants who experience AEs through Week 144
Timepoint [15] 0 0
Up to Week 144
Secondary outcome [16] 0 0
Percentage of participants who discontinue study intervention due to AEs through Week 144
Timepoint [16] 0 0
Up to Week 144

Eligibility
Key inclusion criteria
The key inclusion and exclusion criteria include but are not limited to the following:



* Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL
* Has been receiving BIC/FTC/TAF therapy 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 participant of childbearing potential, not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration
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 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 with laboratory values consistent with cirrhosis
* Has a history of malignancy =5 years prior to providing documented 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 strong and moderate cytochrome P450 3A (CYP3A ) inducers
* Has a documented or known virologic resistance to DOR
* Has taken long-acting HIV therapy at any time (e.g., cabotegravir, lenacapavir)
* 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 except those currently enrolled in the comparator arm of an ongoing DOR/ISL study

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
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
17/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/08/2028
Actual
Sample size
Target
Accrual to date
Final
514
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Holdsworth House Medical Practice ( Site 6200) - Darlinghurst
Recruitment hospital [2] 0 0
St Vincent's Hospital-IBAC ( Site 6203) - Sydney
Recruitment hospital [3] 0 0
Holdsworth House Medical Practice - Brisbane ( Site 6201) - Brisbane
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital-Infectious Diseases Research ( Site 6204) - Brisbane
Recruitment hospital [5] 0 0
Prahran Market Clinic ( Site 6202) - 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
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Nevada
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Chile
State/province [12] 0 0
Araucania
Country [13] 0 0
Chile
State/province [13] 0 0
Maule
Country [14] 0 0
Chile
State/province [14] 0 0
Region M. De Santiago
Country [15] 0 0
Israel
State/province [15] 0 0
Haifa
Country [16] 0 0
Israel
State/province [16] 0 0
Jerusalem
Country [17] 0 0
Israel
State/province [17] 0 0
Ramat Gan
Country [18] 0 0
Israel
State/province [18] 0 0
Tel Aviv
Country [19] 0 0
Japan
State/province [19] 0 0
Aichi
Country [20] 0 0
Japan
State/province [20] 0 0
Tokyo
Country [21] 0 0
Japan
State/province [21] 0 0
Osaka
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Bristol, City Of
Country [23] 0 0
United Kingdom
State/province [23] 0 0
England
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London, City Of
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Wales
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Reading

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 antiretroviral activity of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) at Week 48; and to evaluate the safety and tolerability of a switch to DOR/ISL compared with continued BIC/FTC/TAF, through Week 48. The primary hypotheses are that (1) DOR/ISL is non-inferior to continued BIC/FTC/TAF, 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; and (2) DOR/ISL is superior to BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA =50 copies/mL at Week 48.
Trial website
https://clinicaltrials.gov/study/NCT05630755
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/NCT05630755