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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04223791




Registration number
NCT04223791
Ethics application status
Date submitted
8/01/2020
Date registered
10/01/2020
Date last updated
24/09/2020

Titles & IDs
Public title
Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018)
Scientific title
A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV- 1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
Secondary ID [1] 0 0
2019-000587-23
Secondary ID [2] 0 0
8591A-018
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

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 FDC DOR/ISL

Experimental: DOR/ISL - A fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 96 weeks; and placebo to Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) for 96 weeks

Active Comparator: BIC/FTC/TAF - 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 96 weeks, and placebo to FDC DOR/ISL for 96 weeks


Treatment: Drugs: DOR/ISL
100 mg DOR/ 0.75 ISL FDC tablet taken orally once daily

Treatment: Drugs: BIC/FTC/TAF
50 mg BIC, 200 mg FTC, and 25 mg TAF combined in a single tablet, taken orally once daily

Treatment: Drugs: Placebo to BIC/FTC/TAF
Placebo to BIC/FTC/TAF in a single tablet taken orally, once daily

Treatment: Drugs: Placebo to FDC DOR/ISL
Placebo to FDC DOR/ISL in a tablet taken orally, once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Participants with (Human Immunodeficiency Virus 1 ribonucleic acid ) HIV-1 RNA =50 copies/mL at Week 48 - Percentage of participants with (Human Immunodeficiency Virus 1 ribonucleic acid) 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 adverse events (AEs) up to Week 48 - Percentage of participants with one or more adverse events (AEs) up to Week 48
Timepoint [2] 0 0
Up to 48 weeks
Primary outcome [3] 0 0
Participants who discontinued study intervention due to an AE up to Week 48 - Percentage of participants who discontinued study intervention due to an AE up to Week 48
Timepoint [3] 0 0
Up to 48 weeks
Secondary outcome [1] 0 0
Participants with HIV-1 RNA =50 copies/mL at Week 96 - Percentage of participants with HIV-1 RNA =50 copies/mL at Week 96
Timepoint [1] 0 0
Week 96
Secondary outcome [2] 0 0
Participants with HIV-1 RNA <40 or <50 copies/mL at Week 48 - Percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 48
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Participants with HIV-1 RNA <40 or <50 copies/mL at Week 96 - Percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 96
Timepoint [3] 0 0
Week 96
Secondary outcome [4] 0 0
CD4+ T-cell count at Week 48 - Change from baseline in CD4+ T-cell count at Week 48
Timepoint [4] 0 0
Baseline and Week 48
Secondary outcome [5] 0 0
CD4+ T-cell count at Week 96 - Change from baseline in CD4+ T-cell count at Week 96
Timepoint [5] 0 0
Baseline and Week 96
Secondary outcome [6] 0 0
Participants with evidence of viral drug resistance-associated substitutions at Week 48 - Percentage participants with evidence of viral drug resistance-associated substitutions at Week 48
Timepoint [6] 0 0
Week 48
Secondary outcome [7] 0 0
Participants with evidence of viral drug resistance-associated substitutions at Week 96 - Percentage participants with evidence of viral drug resistance-associated substitutions at Week 96
Timepoint [7] 0 0
Week 96
Secondary outcome [8] 0 0
Change from baseline in body weight at Week 48 - Change from baseline in body weight at Week 48
Timepoint [8] 0 0
Baseline and Week 48
Secondary outcome [9] 0 0
Change from baseline in body weight at Week 96 - Change from baseline in body weight at Week 96
Timepoint [9] 0 0
Baseline and Week 96
Secondary outcome [10] 0 0
Participants with one or more AEs up to Week 96 - Percentage of participants with one or more AEs up to Week 96
Timepoint [10] 0 0
Up to Week 96
Secondary outcome [11] 0 0
Participants who discontinued study intervention due to an AE up to Week 96 - Percentage of participants who discontinued study intervention due to an AE up to Week 96
Timepoint [11] 0 0
Up to Week 96

Eligibility
Key inclusion criteria
- Is HIV-1 positive with plasma (Human Immunodeficiency Virus 1) HIV-1 RNA <50 copies/mL
at screening.

- Has been receiving BIC/FTC/TAF therapy 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;
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has HIV-2 infection

- 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 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

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital ( Site 3807) - Darlinghurst
Recruitment hospital [2] 0 0
Taylor Square Private Clinic ( Site 3804) - Darlinghurst
Recruitment hospital [3] 0 0
Holdsworth House Medical Practice ( Site 3800) - Sydney
Recruitment hospital [4] 0 0
Holdsworth House Medical Practice - Brisbane ( Site 3810) - Brisbane
Recruitment hospital [5] 0 0
Royal Brisbane and Womens Hospital- Infectious Diseases Unit ( Site 3812) - Herston
Recruitment hospital [6] 0 0
The Alfred Hospital ( Site 3802) - Melbourne
Recruitment hospital [7] 0 0
Prahran Market Clinic (PMC) ( Site 3806) - 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 - Herston
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 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
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Austria
State/province [12] 0 0
Steiermark
Country [13] 0 0
Austria
State/province [13] 0 0
Wien
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Finland
State/province [17] 0 0
Uusimaa
Country [18] 0 0
France
State/province [18] 0 0
Ain
Country [19] 0 0
France
State/province [19] 0 0
Alpes-Maritimes
Country [20] 0 0
France
State/province [20] 0 0
Bouches-du-Rhone
Country [21] 0 0
France
State/province [21] 0 0
Hauts-de-Seine
Country [22] 0 0
France
State/province [22] 0 0
Herault
Country [23] 0 0
France
State/province [23] 0 0
Loire-Atlantique
Country [24] 0 0
France
State/province [24] 0 0
Loiret
Country [25] 0 0
France
State/province [25] 0 0
Meurthe-et-Moselle
Country [26] 0 0
France
State/province [26] 0 0
Nord
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
Germany
State/province [28] 0 0
Bayern
Country [29] 0 0
Germany
State/province [29] 0 0
Hessen
Country [30] 0 0
Germany
State/province [30] 0 0
Niedersachsen
Country [31] 0 0
Germany
State/province [31] 0 0
Nordrhein-Westfalen
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Italy
State/province [34] 0 0
Lombardia
Country [35] 0 0
Italy
State/province [35] 0 0
Milano
Country [36] 0 0
Italy
State/province [36] 0 0
Napoli
Country [37] 0 0
Japan
State/province [37] 0 0
Aichi
Country [38] 0 0
Japan
State/province [38] 0 0
Osaka
Country [39] 0 0
Japan
State/province [39] 0 0
Tokyo
Country [40] 0 0
Puerto Rico
State/province [40] 0 0
Ponce
Country [41] 0 0
Puerto Rico
State/province [41] 0 0
Rio Piedras
Country [42] 0 0
Puerto Rico
State/province [42] 0 0
San Juan
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona [Barcelona]
Country [44] 0 0
Spain
State/province [44] 0 0
Barcelona
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Malaga

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
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 regimen of bictegravir/emtricitabine/tenofovir
alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to MK-8591A will be
non-inferior to continued treatment with BIC/FTC/TAF as assessed by the proportion of
participants with HIV-1 ribonucleic acid (RNA) =50 copies/mL at Week 48.
Trial website
https://clinicaltrials.gov/show/NCT04223791
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
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
Other publications