Merck Stops Phase 2 Clinical Trial of Once-Weekly Investigational Combination of MK-8507 and Islatravir for the Treatment of HIV-1
Merck announced that it has stopped the Phase 2 IMAGINE-DR clinical trial (MK-8507-13), which is evaluating the investigational combination of MK-8507, a non-nucleoside reverse transcriptase inhibitor, and islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, as a once-weekly oral treatment for HIV-1 infection.
Decreases in total lymphocyte and CD4+ T-cell counts were observed in study participants randomized to receive ISL+MK-8507.
A review by the external Data Monitoring Committee (eDMC) determined that this effect was related to treatment with the combination of ISL+MK-8507; the greatest decreases were seen in the arms of the study receiving the highest doses of MK-8507 (200 mg and 400 mg). At the recommendation of the eDMC, Merck is stopping dosing in the trial, with continued monitoring of study participants.
The IMAGINE-DR clinical trial was a Phase 2, randomized, controlled, double-blind, dose-ranging study, designed to evaluate a switch to MK-8507 and ISL in combination as a once-weekly oral treatment in adults with HIV-1 who have been virologically suppressed for greater than or equal to six months on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily. The study had been fully enrolled with 161 participants and was ongoing.
In response to the findings from the MK-8507-013 study, Merck conducted a review of trends in total lymphocyte and CD4+ T-cell counts in company-sponsored clinical trials of ISL across all indications and dosing regimens. A dose-dependent decrease in lymphocyte counts was observed in an ongoing Phase 2 trial (MK-8591-016), which is evaluating monthly ISL (60 mg and 120 mg) for PrEP in participants at low-risk of HIV-1 infection. In this population of HIV-1 uninfected participants, the mean decreases were in the normal range and there was no increase in clinical adverse events (AEs) related to infection. In addition, a small, treatment related mean decrease in CD4+ T-cell counts was observed through Week 48 in two Phase 3 trials, ILLUMINATE SWITCH A and ILLUMINATE SWITCH B (MK-8591A-017 and MK-8591A-018), which are evaluating doravirine 100 mg in combination with ISL 0.75 mg daily (DOR/ISL) in HIV-1 virologically suppressed participants. There was no increased incidence of AEs related to infections in participants receiving DOR/ISL relative to comparators through Week 48. Investigators for these trials have been informed and the trials are continuing. Full results from ILLUMINATE SWITCH A and ILLUMINATE SWITCH B will be presented at an upcoming medical meeting.
Merck and is continuing with development of islatravir across a range of settings including in treatment of patients living with HIV and in pre-exposure prophylaxis (PrEP). As previously reported from the ILLUMINATE SWITCH A and ILLUMINATE SWITCH B Phase 3 clinical trials at 48 weeks, both trials met their primary efficacy endpoint of percentage of participants with HIV-1 RNA levels ≥50 copies/mL, demonstrating that antiviral efficacy was comparable between DOR/ISL and different antiretroviral therapy regimens (ILLUMINATE SWITCH A) and between DOR/ISL and Gilead’s Biktarvy (bictegravir/emtricitabine/tenofovir) (ILLUMINATE SWITCH B).
Fonte: press release