MK-8591A-054: An open-label phase 3 clinical study with once-daily Doravirine/Islatravir (DOR/ISL [100 mg/0.25 mg]) for the treatment of HIV-1 infection in participants who previously received once-daily DOR/ISL (100 mg/0.75 mg) in a phase 3 clinical study

Summary description of the study

The entire study is expected to last approximately 3 years and around 1300 patients will participate worldwide. The aim of this study is to investigate the safety, tolerability, efficacy, and viral resistance of DOR/ISL. Active treatment phase: In this study, all participants will receive DOR/ISL. DOR/ISL is a single tablet taken orally once daily (100 mg Doravirine/0.25 mg Islatravir). Unless the medication needs to be stopped prematurely, the active treatment phase lasts approximately 2 years. About 6 weeks after the last intake of the study medication, participants will be invited again 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 come to visits at the study center as agreed with the study physician (approximately 10 times during the two-year active treatment phase as well as at least once before and after).

During the study appointments, various measures and examinations may take place, such as: dispensing of study medication, questioning by the study team, recording of adverse events, checking adherence to medication intake, taking blood or urine samples, or a physical examination. For female study participants, a pregnancy test will also be conducted and the currently used contraceptive method will be discussed.

(BASEC)

Disease under investigation

The number of people infected with HIV (HIV: Human Immunodeficiency Virus) worldwide was estimated to be 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. If untreated, an HIV infection leads to AIDS and ultimately to death. Due to the good medication therapy options available today, it is now possible to control the virus in affected individuals so effectively that their health status, quality of life, and life expectancy improve significantly. As these therapies are usually applied over a very long period, long-term tolerability and safety have become increasingly important factors. The experimental medication in this study is a tablet medication that contains two active ingredients: Doravirine and Islatravir (DOR/ISL or MK-8591A). Doravirine is a new active ingredient already approved in many countries in the NNRTI class, while Islatravir is a promising, yet unapproved substance that is to be investigated as a combination partner of Doravirine 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. The current non-clinical and clinical data also support further investigation of the lower Islatravir dosing of 0.25 mg applied in this study in phase 3 studies. Adult study participants with an HIV-1 infection will be examined, who have previously received the study medication DOR/ISL (with the higher Islatravir dosing of 0.75 mg) in a prior MSD-sponsored study and agree to continue treatment until it becomes available on the market and is reimbursed by health insurance.

(BASEC)

Sponsor

MSD Merck Sharp & Dohme AG Luzern

(BASEC)

Name of the authorising ethics committee (for multicentre studies, only the lead committee)

Ethics Committee Geneva

(BASEC)

Date of authorisation

31.05.2023

(BASEC)

Results of the trial