What's Happening?
The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network has initiated a phase I/II clinical trial, IMPAACT 2041, to assess the pharmacokinetics and safety of glecaprevir/pibrentasvir (GLE/PIB) in pregnant women with hepatitis
C virus (HCV) mono-infection or HCV/HIV co-infection. This study addresses a significant gap in research, as direct-acting antivirals (DAAs) like GLE/PIB, while highly effective in non-pregnant populations, have limited data regarding their use during pregnancy. The trial aims to enroll up to 30 pregnant participants, with a target of at least 20 pharmacokinetics (PK)-evaluable participants, to understand how pregnancy-related physiological changes might affect drug absorption, distribution, metabolism, and elimination. Participants will be screened and enrolled between 14 and 32 weeks of gestation and will receive GLE/PIB once daily for 8 weeks. The study will also follow infants for at least 12 weeks after exposure to GLE/PIB.
Why It's Important?
The increasing prevalence of HCV infection among young adults, including those who may become pregnant, has led to a corresponding rise in infants exposed to and infected with HCV. Despite recommendations for universal HCV screening during pregnancy, a clear pathway for immediate treatment has been lacking. Initiating HCV treatment during pregnancy offers several benefits, including higher patient engagement in care, more comprehensive health insurance coverage extending postpartum, and the potential to complete therapy before delivery, thereby reducing the risk of vertical transmission to the infant. This study is crucial for informing clinical guidelines and practices, potentially leading to updated FDA labels for GLE/PIB use in pregnancy. The findings could significantly impact public health efforts to eliminate HCV, both in the United States and globally, by providing a more effective model of care for pregnant women and their infants.
What's Next?
The IMPAACT 2041 study will continue to enroll pregnant participants and conduct pharmacokinetic and safety assessments. An interim review will be performed after five participants have completed at least one intensive PK assessment to check initial GLE/PIB exposures. The primary objectives are to describe the PK of GLE and PIB in pregnant women compared to historical data from non-pregnant women and to describe the safety of GLE/PIB during treatment and through 10 weeks postpartum. Secondary objectives include evaluating sustained virologic response (SVR12) among pregnant women, measuring the frequency of perinatal HCV transmission, and describing pregnancy outcomes and infant safety. The data collected from this study, combined with results from other ongoing studies on HCV treatment in pregnancy, will be instrumental in developing professional society guidelines from organizations like AASLD/IDSA, ACOG, and SMFM, potentially leading to a recommendation to treat HCV infection during pregnancy.
Beyond the Headlines
The IMPAACT 2041 study highlights a broader challenge in pharmaceutical research: the historical exclusion of pregnant women from clinical trials. This exclusion often leaves healthcare providers and patients without evidence-based guidance for treating various conditions during pregnancy, forcing difficult decisions based on limited data. The IMPAACT Network's commitment to conducting such research, building on its extensive experience with HIV treatment in pregnant women, signifies a positive shift towards more inclusive and comprehensive drug development. The ethical considerations involved in designing trials for pregnant populations, balancing potential risks to both mother and fetus with the benefits of treatment, are complex. This study's design, including careful selection of gestational age for enrollment and detailed monitoring of both maternal and infant outcomes, reflects a nuanced approach to addressing these challenges and ensuring the well-being of this vulnerable population.
