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

Not Applicable

Not yet recruiting

• Conditions: Hepatitis C
• Interventions: Drug: Glecaprevir/pibrentasvir

• Registration Number: NCT07040319
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-13
• Study First Submitted QC: 2025-06-24
• Last Update Submitted: 2025-06-24
• Study First Posted: 2025-06-27
• Last Update Posted: 2025-06-27
• Study Start: 2025-11-28
• Primary Completion: 2027-07-30
• Study Completion: 2027-07-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 30

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

• Previous treatment for hepatitis C with a DAA regimen

• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GLE/PIB	Glecaprevir/pibrentasvir	Pregnant participants will take three (3) GLE/PIB fixed-dose combination tablets orally once daily with food for eight weeks

Primary Outcome Measures

Name	Time	Method
Geometric mean AUC0-24h	At weeks 3 & 6	Area under the curve from start of dose to 24 hours post dose
Geometric mean Cmax	At weeks 3 & 6	Peak concentration from start of dose to 24 hours post dose
Geometric mean C24h	At weeks 3 & 6	Concentration at 24 hours post dose
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

Name	Time	Method
Percentage of pregnant/postpartum participants with sustained virologic response (SVR12)	12 weeks after planned treatment completion	defined as unquantifiable hepatitis C RNA (less than the lower limit of quantification \[\<LLOQ\])
Percentage of pregnant participants with spontaneous abortions or miscarriage	At birth/delivery	(\<20 weeks gestation)
Percentage of pregnant participants with stillbirths	At birth/delivery	(≥20 weeks gestation)
Percentage of infants small for gestational age	At birth/delivery	\<10th percentile
Percentage of infants with low birth weight	At birth/delivery	\<2500 g
Percentage of pre-term births	At birth/delivery	\<37 weeks gestation
Percentage of pregnancies with occurrence of any of the following adverse pregnancy events	At birth/delivery	spontaneous abortion or miscarriage, stillbirth, small gestational age, low birth weight, or preterm birth
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 8 or more weeks of age

Trial Locations

Locations (9)

USC LA; 🇺🇸 Los Angeles, California, United States

David Geffen School of Medicine at UCLA; 🇺🇸 Los Angeles, California, United States

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins University Baltimore; 🇺🇸 Baltimore, Maryland, United States

Bronx-Lebanon Hospital Center; 🇺🇸 Bronx, New York, United States

Jacobi Medical Center; 🇺🇸 Bronx, New York, United States

SUNY Stony Brook; 🇺🇸 Stony Brook, New York, United States

Baylor College of Medicine//Texas Children's Hospital; 🇺🇸 Houston, Texas, United States