Study of the Pharmacokinetics and Safety of Glecaprevir/Pibrentasvir Initiated in Pregnancy in Women With Hepatitis C With and Without HIV

Phase I/II Study of the Pharmacokinetics and Safety of Glecaprevir/Pibrentasvir Initiated in Pregnancy in Women With Hepatitis C With and Without HIV

This is a Phase I/II, multi-site, open-label, single arm study to describe the pharmacokinetics (PK) and safety of glecaprevir/pibrentasvir (GLE/PIB) initiated during pregnancy in women with hepatitis C virus (HCV) infection (acute or chronic) with or without HIV and to evaluate safety for their infants through 10 weeks postpartum.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Glecaprevir/pibrentasvir

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: IMPAACT ClinicalTrials.gov Coordinator; Email: impaact.ctgov@fstrf.org
• Study Contact Backup: Name: Katie McCarthy; Phone Number: 919-321-3326; Email: kmccarthy@fhi360.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • David Geffen School of Medicine at UCLA
      • Contact: Misciel Macaraig, BA, CCRC; Phone Number: 310-206-6369; Email: mbmacaraig@mednet.ucla.edu
    • Los Angeles, California, United States, 90089
      • Recruiting
      • USC LA
      • Contact: Yvonne Morales, LVN; Phone Number: 323-865-1561; Email: ytr@usc.edu
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Denver
      • Contact: Carrie Chambers, RN; Phone Number: 720-777-4424; Email: carrie.chambers@childrenscolorado.org
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • Univ. of Florida Jacksonville
      • Contact: Adnan Shabbir; Phone Number: 904-244-3796; Email: adnan.shabbir@jax.ufl.edu
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Recruiting
      • Lurie Children's Hospital of Chicago
      • Contact: Rasima Cehic, RN; Phone Number: 312-227-8273; Email: rcehic@luriechildrens..org
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University Baltimore
      • Contact: Amanda Haines, BSN, RN; Phone Number: 443-287-8888; Email: ahaines8@jhmi.edu
  • New York
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • SUNY Stony Brook
      • Contact: Barsha Chakraborty, MPH; Phone Number: 631-444-8225; Email: barsha.chakraborty@stonybrookmedicine.edu
    • The Bronx, New York, United States, 10461
      • Not yet recruiting
      • Jacobi Medical Center
      • Contact: Marlene Burey, RN, PNP; Phone Number: 718-918-4783; Email: marlene.burey@nychhc.org
    • The Bronx, New York, United States, 10457
      • Recruiting
      • Bronx-Lebanon Hospital Center
      • Contact: Martha Cavallo, PNP; Phone Number: 718-960-1016; Email: mcavallo@bronxcare.org
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine//Texas Children's Hospital
      • Contact: Mariam Pontifes; Phone Number: 832-822-1268; Email: mepontif@texaschildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Of legal age or circumstance to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with institutional review board/ethics committee (IRB/EC) policies and procedures
• Willing and able to provide written informed consent for their own and their infant's study participation
• At entry, 16-45 years of age (inclusive)
• At entry, gestational age of 14-32 weeks, defined as greater than 13 weeks plus six days and less than or equal to 32 completed weeks gestation, as determined by the site investigator based on best obstetric estimate
• At screening and at study entry, no evidence of multiple gestation, fetal anomalies, or intrauterine fetal growth restriction, as determined by the site investigator based on ultrasound
• At screening, detectable HCV RNA test result based on testing of a specimen collected within 30 days prior to entry
• At screening, negative test results for hepatitis B surface antigen based on testing of a specimen collected within 30 days prior to entry

• At screening (i.e., from specimens collected within 30 days prior to entry), has normal, grade 1, grade 2, or grade 3 results for the following

  • Aspartate aminotransferase (AST) (<10.0 x ULN)
  • Alanine aminotransferase (ALT) (<10.0 x ULN)

• At screening (i.e., from specimens collected within 30 days prior to entry), has normal, grade 1, or grade 2 results for the following

  • Hemoglobin (≥8.5 g/dL)
  • Creatinine (≤1.8 x ULN)

• At screening (i.e., from specimens collected within 30 days prior to entry), has normal or grade 1 results for the following

  • International normalized ratio (INR) (<1.5 x ULN)
  • Platelet count (≥100,000 cells/mm3)
  • Total bilirubin (<1.6 x ULN)
• HIV status determined based on testing meeting the requirements specified in protocol
• For pregnant participants living with HIV: has a suppressed HIV viral load (HIV-1 RNA below the limit of quantification of the assay) on an ARV regimen for at least 30 consecutive days prior to entry that does not include efavirenz, etravirine, cobicistat, or any protease inhibitor (e.g., atazanavir, darunavir, lopinavir, ritonavir), as determined by the site investigator based on available medical records
• At entry, expects to remain in the geographic area of the study site during pregnancy and for 10 weeks postpartum (or for 20 weeks post-entry, depending on gestational age at entry), as determined by the site investigator based on pregnant participant report

Exclusion Criteria:

• Any previous treatment for hepatitis C, including HCV DAAs or interferon-based treatment

• High risk of preterm delivery, defined as either of the following:

  • History of spontaneous preterm delivery at less than 34 weeks, as determined by the site investigator based on pregnant participant report and available medical records, or
  • Shortened cervix less than 20 mm if noted on ultrasound during the current pregnancy, as determined by the site investigator based on available medical records
• Receipt of any prohibited medication, within 14 days prior to entry, as determined by the site investigator based on pregnant participant report and available medical records

• Any of the following liver-related conditions:

  • Clinical diagnosis of acute hepatitis not otherwise attributable to hepatitis C with AST or ALT ≥2.5 x ULN
  • Evidence of decompensated cirrhosis including history of or present variceal hemorrhage, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatocellular carcinoma, hepatorenal syndrome, or hepatopulmonary syndrome
• Has any other documented or suspected clinically significant medical condition or any other condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLE/PIB; Pregnant participants will take three (3) GLE/PIB fixed-dose combination tablets orally once daily with food for eight weeks	Drug: Glecaprevir/pibrentasvir; 100 mg glecaprevir and 40 mg pibrentasvir for a total daily dose of glecaprevir 300 mg/pibrentasvir 120 mg; Other Names: GLE/PIB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean AUC0-24h	Area under the curve from start of dose to 24 hours post dose	At weeks 3 & 6
Geometric mean Cmax	Peak concentration from start of dose to 24 hours post dose	At weeks 3 & 6
Geometric mean C24h	Concentration at 24 hours post dose	At weeks 3 & 6
Percentage of pregnant/ postpartum participants who experience a grade 3 or higher adverse event assessed as related to study drug		Initiation of treatment to a) completion of treatment and b) latter of 10 weeks post-partum or 20 weeks post treatment initiation
Percentage of pregnant participants who experience a serious adverse event assessed as related to study drug		Initiation of treatment to a) completion of treatment and b) latter of 10 weeks post-partum or 20 weeks post treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of pregnant/postpartum participants with sustained virologic response (SVR12)	defined as unquantifiable hepatitis C RNA (less than the lower limit of quantification [<LLOQ])	12 weeks after planned treatment completion
Percentage of pregnant participants with spontaneous abortions or miscarriage	(<20 weeks gestation)	At birth/delivery
Percentage of pregnant participants with stillbirths	(≥20 weeks gestation)	At birth/delivery
Percentage of infants small for gestational age	<10th percentile	At birth/delivery
Percentage of infants with low birth weight	<2500 g	At birth/delivery
Percentage of pre-term births	<37 weeks gestation	At birth/delivery
Percentage of pregnancies with occurrence of any of the following adverse pregnancy events	spontaneous abortion or miscarriage, stillbirth, small gestational age, low birth weight, or preterm birth	At birth/delivery
Percentage of infants with a congenital abnormality		At birth/delivery
Percentage of infants with a grade 5 adverse event		From birth through 10 weeks of age
Percentage of infants with Grade 3 or higher adverse event assessed as related to study drug		From birth through 10 weeks of age
Percentage of infants with a serious adverse events assessed as related to study drug		From birth through 10 weeks of age
Percentage of occurrence of any of the following in infants: grade 5 adverse event within 28 days of birth, grade 3 or higher adverse event assessed as related to study drug, or severe adverse event assessed as related to study drug		From birth through 10 weeks of age
Median weight of infants		At birth and 10 weeks of age
Median length of infants		At birth and 10 weeks of age
Median head circumference of infants		At birth and 10 weeks of age
Percentage of infants with quantifiable hepatitis C RNA		At 10 or more weeks of age

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH); AbbVie

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: June 13, 2025
• First Submitted That Met QC Criteria: June 24, 2025
• First Posted (Actual): June 27, 2025

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: HIV; Pregnancy; Hepatitis C; Glecaprevir/Pibrentasvir
• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; Flaviviridae Infections; Hepatitis; Hepatitis C; glecaprevir and pibrentasvir
• Other Study ID Numbers: IMPAACT 2041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.; For what types of analyses?; To achieve aims in the proposal approved by the IMPAACT Network.; By what mechanism will data be made available?; Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https:// www.impaactnetwork.org/ resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No