A randomized, active-controlled, open-label Phase 3 clinical study to assess a switch to Doravirin/Islatravir (DOR/ISL 100 mg/0.25 mg) once daily in participants with HIV-1 infection who are virologically suppressed on antiretroviral therapy.
Summary description of the study
The entire study is expected to last approximately 2.5 years and approximately 501 patients will participate worldwide. The aim of this study is to investigate the safety, efficacy, and tolerability of switching from an existing HIV therapy to the study medication DOR/ISL. Active treatment phase: Participants will be randomly assigned to one of two groups (i.e., randomized), with twice as many people included in the first group as in the second group (2:1): - Group 1: Switch to DOR/ISL for approximately two years - Group 2: The existing antiretroviral therapy will continue for one more year, after which there will be a switch to a one-year treatment with DOR/ISL. About 6 weeks after the active treatment phase, participants will be invited for a follow-up visit at the study center.
(BASEC)
Intervention under investigation
After thorough information, precise eligibility assessment, and collection of medical history, patients will be included in the study. Thereafter, participants will attend visits at the study center as agreed with the study physician (approximately 12 times during the two-year active treatment phase).
During the study visits, various measures and examinations may occur, such as: blood or urine sample collection, completion of questionnaires, examination of vital signs (pulse, blood pressure, etc.) as well as an electrocardiogram (ECG).
Administration of the study medication DOR/ISL:
DOR/ISL is a single tablet and is taken orally once daily.
(BASEC)
Disease under investigation
Adult study participants with an HIV-1 infection will be examined, who have been virologically suppressed for at least three months on current therapy and show no signs of treatment failure (HIV: Human Immunodeficiency Virus). The number of people infected with HIV worldwide was estimated at over 38 million in 2021. The number of new HIV infections in 2021 is also very high at 1.5 million people worldwide. HIV is still not curable. Untreated, an HIV infection leads to AIDS and ultimately death. Due to the good medication options available today, it is now possible to control the virus so effectively that the health status, as well as the quality of life and life expectancy of those affected, improve significantly. As these therapies are usually applied over a very long time, long-term tolerability and safety have become increasingly important factors. The experimental medication in this study is a tablet containing two active ingredients: Doravirin and Islatravir (DOR/ISL). Doravirin is a new active ingredient of the NNRTI class already approved in most countries, while Islatravir is a promising, yet unapproved substance that is to be investigated as a combination partner of Doravirin in this Phase 3 study. DOR/ISL has the potential to simplify HIV therapy for patients due to its new mechanism of action and also appears to have a favorable safety profile.
(BASEC)
• HIV-1 infection with an HIV viral load of < 50 HIV-1 RNA copies/ml at the time of the study eligibility test • Stable, uninterrupted oral combination therapy (of two or three medications) with at least 3 months of stable suppression of viral load to below 50 HIV-1 RNA copies/ml prior to signing the patient information • No prior failure of an antiviral treatment (BASEC)
Exclusion criteria
• HIV-2 infection, active HBV infection, or chronic HCV infection with laboratory values corresponding to cirrhosis • Active AIDS-defining opportunistic infection within 30 days prior to screening • Hypersensitivity or other contraindication to any of the study medications (BASEC)
Trial sites
Basel, Bellinzona, Bern, Geneva, Lausanne, Zurich
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Lucerne
(BASEC)
Contact
Contact Person Switzerland
Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG, Lucerne
(BASEC)
General Information
Merck Sharp & Dohme LLC
(ICTRP)
Scientific Information
Merck Sharp & Dohme LLC
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
24.01.2023
(BASEC)
ICTRP Trial ID
NCT05631093 (ICTRP)
Official title (approved by ethics committee)
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 (BASEC)
Academic 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 (ICTRP)
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) (ICTRP)
Disease under investigation
HIV-1 Infection (ICTRP)
Intervention under investigation
Drug: ARTDrug: DOR/ISL (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:
- Is Human Immunodeficiency Virus-1 (HIV-1) positive with plasma HIV-1 Ribonucleic
Acid (RNA) <50 copies/mL at screening
- Has been receiving continuous, stable oral 2-drug or 3-drug combination ( PK
booster) antiretroviral therapy 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
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 Doravine (DOR) (ICTRP)
not available
Primary and secondary end points
Percentage of Participants With HIV-1 RNA =50 Copies/mL at Week 48;Percentage of Participants With One or More Adverse Events (AEs) at Week 48;Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48 (ICTRP)
Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48;Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48;Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96;Participants With HIV-1 RNA <200 Copies/mL at Week 144;Percentage of Participants With HIV-1 RNA =50 Copies/mL at Week 96;Percentage of Participants With HIV-1 RNA =50 Copies/mL at Week 144;Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96;Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144;Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48;Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96;Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144;Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96;Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144;Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48;Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48;Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48;Participants With One or More AEs at Week 96;Participants With One or More AEs at Week 144;Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96;Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144;Percentage of Participants With One or More AEs From Week 48 up to Week 96;Percentage of Participants With One or More AEs From Week 48 up to Week 144;Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96;Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144 (ICTRP)
Registration date
18.11.2022 (ICTRP)
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Medical Director, Merck Sharp & Dohme LLC (ICTRP)
Secondary trial IDs
MK-8591A-051, jRCT2031220698, U1111-1283-3894, 2022-502127-22-00, 2022-502127-22, 8591A-051 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT05631093 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available