Clinical Study of Islatravir (ISL) and Ulonivirine (ULO) in Individuals with HIV-1 after Switching from Bictegravir/Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF)

Résumé de l'étude

The main objective of this study is to investigate and evaluate the safety, tolerability, and efficacy of Islatravir (ISL) and Ulonivirine (ULO) compared to Bictegravir/Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF), and to assess how well the switch from BIC/FTC/TAF to ISL and ULO works. Your blood values will be checked regarding HIV-1 levels, white blood cells, and other immune system cells. The side effects occurring during the study will also be evaluated to assess the safety and tolerability of ISL and ULO. Participants in this study will be adults with an HIV-1 infection who have been treated with BIC/FTC/TAF for at least 6 months prior to the study. These individuals must take a medication daily, which can lead to pill fatigue and poor adherence. The experimental medication in this phase 2 study consists of two tablet-form medications, each containing an active ingredient: ISL and ULO. Neither ISL nor ULO is an approved substance, but both are promising for the treatment of HIV-1. Both medications use several different methods to prevent the replication of HIV and can thus reduce the amount of HIV virus in the body. The treatment with ULO and ISL has the potential to simplify HIV therapy for affected individuals due to weekly administration, provide more anonymity, and ultimately improve treatment outcomes. Both ISL and Ulonivirine also have a favorable safety and tolerability profile. The entire study is expected to last about 2.5 years, with approximately 150 participants worldwide. About 20 participants will be involved in Switzerland.

(BASEC)

Intervention étudiée

After thorough explanation and subsequent consent from the participants, the pre-examination and clarification period begins. This lasts a maximum of 45 days. Subsequently, the participant will be included in the study and randomly assigned in a 1:1 ratio to one of the following two groups:

Group 1: Participants will receive ISL and ULO for about 2 years.

Group 2: Participants will continue to receive BIC/FTC/TAF for about one year and then switch to ISL and ULO for another year.

During the study participation, participants will visit the study center approximately 12 times during the two-year active treatment phase, as well as at least once before and after.

ISL and ULO will be administered in tablet form and taken once weekly. BIC/FTC/TAF will also be administered in tablet form and taken once daily.

This study is referred to as an "open-label" study. This means that both the participants and the study doctor and sponsor know which group they have been assigned to and thus whether they are receiving ISL and ULO or BIC/FTC/TAF.

During study appointments, various measures and examinations may take place, such as electrocardiograms (ECG), blood and urine tests, imaging studies (X-rays, bone scans), assessment of general health status, recording of adverse events, and discussions with medical staff. Current contraceptive methods will also be discussed, and a pregnancy test will be conducted for female study participants. The study team may also contact participants between visits and after the completion of the study medication to inquire about their health status.

(BASEC)

Maladie en cours d'investigation

The number of people infected with HIV (Human Immunodeficiency Virus) worldwide was estimated at 39 million in 2023. The number of new HIV infections is also very high, with over one million people per year globally. Despite significant advances in therapy, HIV remains incurable to this day. Untreated, an HIV infection leads to AIDS and ultimately to death. Due to the good medication options for antiretroviral therapy (ART) 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. ART is the standard treatment for HIV and involves the use of a combination of three antiretroviral medications to suppress HIV replication, reduce its viral load in the body, and maintain a healthy immune system. Since these therapies are typically administered over a very long period, long-term tolerability and safety have become increasingly important factors. In recent years, a 2-drug approach has emerged that is comparable in efficiency to the earlier 3-drug treatment. The reduction from 3 to 2 medications has shown improved tolerability and treatment adherence. Both help to maintain virological suppression. Additionally, a therapy that needs to be taken only once weekly instead of daily can offer additional benefits for lifelong treatment, such as easier administration, improved treatment adherence, treatment anonymity, and long-term acceptance. Treatment adherence is particularly crucial for the development of resistance and the increased mortality in people with HIV-1.

(BASEC)

Sponsor

Merck Sharp & Dohme AG

(BASEC)

Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)

Commission cantonale d'éthique du Tessin

(BASEC)

Date d'approbation du comité d'éthique

23.04.2025

(BASEC)

Résultats de l'essai