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

Official title

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

Overview

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.

Interventions

• Drug Glecaprevir/pibrentasvir
  100 mg glecaprevir and 40 mg pibrentasvir for a total daily dose of glecaprevir 300 mg/pibrentasvir 120 mg

Primary outcome measures

• Geometric mean AUC0-24h [Time frame: At weeks 3 & 6]
• Geometric mean Cmax [Time frame: At weeks 3 & 6]
• Geometric mean C24h [Time frame: At weeks 3 & 6]
• Percentage of pregnant/ postpartum participants who experience a grade 3 or higher adverse event assessed as related to study drug [Time frame: 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 [Time frame: 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 (12)

• Percentage of pregnant/postpartum participants with sustained virologic response (SVR12) [Time frame: 12 weeks after planned treatment completion]
• Percentage of pregnant participants with spontaneous abortions or miscarriage [Time frame: At birth/delivery]
• Percentage of pregnant participants with stillbirths [Time frame: At birth/delivery]
• Percentage of infants small for gestational age [Time frame: At birth/delivery]
• Percentage of infants with low birth weight [Time frame: At birth/delivery]
• Percentage of pre-term births [Time frame: At birth/delivery]
• Percentage of pregnancies with occurrence of any of the following adverse pregnancy events [Time frame: At birth/delivery]
• Percentage of infants with a congenital abnormality [Time frame: At birth/delivery]
• Percentage of infants with a grade 5 adverse event [Time frame: From birth through 10 weeks of age]
• Percentage of infants with Grade 3 or higher adverse event assessed as related to study drug [Time frame: From birth through 10 weeks of age]
• Percentage of infants with a serious adverse events assessed as related to study drug [Time frame: 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 [Time frame: From birth through 10 weeks of age]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• USC LA — Los Angeles
• David Geffen School of Medicine at UCLA — Los Angeles
• University of Colorado Denver — Aurora
• Univ. of Florida Jacksonville — Jacksonville
• Lurie Children's Hospital of Chicago — Chicago
• Johns Hopkins University Baltimore — Baltimore
• SUNY Stony Brook — Stony Brook
• Bronx-Lebanon Hospital Center — The Bronx
• … and 2 more centers

Identifiers

NCT: NCT07040319 · IMPAACT 2041

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗