LOC-IMPAACT Leadership Group Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant Women in the US

PROJECT SUMMARYRemdesivir, the first drug with preliminary evidence of efficacy for treatment of COVID-19, has recently beenawarded Emergency Use Authorization from the FDA for use in hospitalized patients with documented COVID-19. There are no documented pharmacokinetic (PK) and limited safety data available regarding use inpregnancy. The physiological changes associated with pregnancy can have a dramatic impact on drugdisposition, and use of therapeutic agents during pregnancy poses unique safety concerns. The aims of theproposed Phase IV prospective, open label, non-randomized study are to evaluate the PK (Specific Aim 1) andsafety (Specific Aim 2) of remdesivir provided through a compassionate use program or open access protocolin 20 hospitalized pregnant women for treatment of symptoms related to COVID-19, using a well-establishedstudy approach and leveraging the extensive infrastructure of the NIH-sponsored International MaternalPediatric Adolescent AIDS Clinical Trials (IMPAACT) Network and in collaboration with Gilead Sciences. Thestudy will be conducted at multiple experienced IMPAACT-affiliated sites in the US with proven access to thestudy population. Hospitalized pregnant women >18 years of age with COVID-19 scheduled to receiveremdesivir as part of clinical care will be eligible for enrollment if willing and able to provide informed consent orif a legally recognized representative can do so on her behalf. The primary outcome measure will be acomparison of remdesivir PK parameters from study participants (pregnant women) with those in non-pregnantadults. The primary PK endpoints are remdesivir and its major metabolite, GS-441524, AUC0-24h at Day 1, andGS-441524 AUCtau after last dose. Intensive and sparse sampling remdesivir concentrations will be used in apopulation PK analysis to assess the impact of covariates such as stage of pregnancy and severity of COVID-19 disease on remdesivir PK parameters. Plasma remdesivir and GS-441524 concentrations will be quantifiedin the laboratory being used for ongoing Gilead-supported studies of remdesivir in non-pregnant adults,ensuring comparability. At entry and after the last dose, safety monitoring will include liver and renal functiontests and complete blood count (if not obtained within 24 hours for clinical care) and medical record Abstract: Ionfor other laboratory test results and clinical events. Medical record Abstract: Ion for laboratory test results andclinical events will also be performed at 4 weeks postdosing and after labor and delivery. The proposed studywill provide urgently needed pregnancy-specific clinical pharmacology data that will ensure that remdesivir canbe used safely and effectively in pregnant women as rapidly as possible. This research could also serve as amodel to rapidly provide pregnancy PK and safety data for other COVID- therapeutics as they becomeavailable.