The US Food and Drug Administration (FDA) has placed clinical holds on trials analysing Merck’s (MSD) islatravir (MK-8591) for human immunodeficiency virus 1 (HIV-1) treatment.
An experimental inhibitor of nucleoside reverse transcriptase translocation, islatravir is being analysed to prevent and treat HIV-1.
The FDA put a hold on the investigational new drug applications (INDs) for islatravir’s oral and implant formulations for HIV-1 pre-exposure prophylaxis (PrEP), injectable formulation for treating and preventing HIV-1 and the oral once-a-day doravirine plus islatravir (DOR/ISL) for treating HIV-1.
Merck noted that the clinical hold is based on reports of a drop in total lymphocyte and CD4+ T-cell counts in some subjects treated with islatravir in trials.
As reported earlier, the company had suspended subject dosing in the Phase II IMAGINE-DR trial of islatravir plus MK-8507 and stopped enrolment in two Phase III PrEP studies, MK-8591-022 and MK-8591-024, involving once-monthly doses of islatravir.
In trials under complete clinical hold, dosing of subjects with oral and implant and injectable doses of islatravir will be stopped and CD4+ T-cell and total lymphocyte counts will be analysed to check if they have recovered.
Subjects in the PrEP trials will receive approved, once-daily, oral doses of the drug.
Furthermore, individuals enrolled and have begun the therapy in the trials of DOR/ISL under partial clinical hold, will continue to receive the trial drug.
During the partial clinical hold, no new subjects will be analysed or randomised in trials of DOR/ISL.
The company communicated the latest development to trial investigators.
The studies placed on full clinical hold include MK-8591-016, IMPOWER 22, IMPOWER 24, MK-8591-034, MK-8591-035 and MK-8591-043.
Furthermore, the trials of DOR/ISL under partial clinical hold include MK-8591-011, ILLUMINATE SWITCH A, ILLUMINATE SWITCH B, ILLUMINATE THE, ILLUMINATE NAIVE, ILLUMINATE YOUTH and MK-8591A-033
Merck Research Laboratories Global Clinical Development infectious diseases vice-president Dr Joan Butterton said: “Merck continues to investigate the potential of islatravir and nucleoside reverse transcriptase translocation inhibitors and remains committed to helping to address unmet needs in HIV treatment and prevention.”
Earlier, Merck decided to halt the dosing of subjects in the Phase II IMAGINE-DR trial of islatravir and MK-8507 for HIV-1 infection treatment.