Hepatitis C
Conditions
Keywords
HIV, Hepatitis C, Pregnancy, Glecaprevir/Pibrentasvir
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.
Interventions
100 mg glecaprevir and 40 mg pibrentasvir for a total daily dose of glecaprevir 300 mg/pibrentasvir 120 mg
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 10 or more weeks of age | — |
Countries
United States
Contacts
CONTACTIMPAACT ClinicalTrials.gov Coordinator
CONTACTKatie McCarthy
Outcome results
None listed