Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy (STORC)

Safety, Tolerability, and Outcomes of Velpatasvir/SofosbuviR in Treatment of Chronic Hepatitis C Virus During Pregnancy (STORC)

This is a multicenter, single arm study of Sofosbuvir/Velpatasvir (SOF/VEL) for treatment of chronic hepatitis C infection during pregnancy. Treatment will be initiated during the second or third trimester in approximately 100 pregnant people. Maternal participants will take one SOF/VEL tablet once daily for 12 weeks (84 days) and followed until 12 weeks after treatment completion (postpartum). Infants will be followed from birth until one year of age. The primary objectives are to evaluate the sustained virologic response 12 weeks after completion of SOF/VEL treatment (SVR12) in participants treated during pregnancy and to evaluate impact of antenatal treatment with SOF/VEL on the gestational age at delivery.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis C, Chronic; Pregnancy; Infection
• Intervention / Treatment: Drug: Sofosbuvir/Velpatasvir 400 MG-100 MG Oral Tablet

Detailed Description

This is a phase 4, multicenter study, single arm study of Sofosbuvir/Velpatasvir (SOF/VEL) for treatment of chronic hepatitis C infection during pregnancy. Participants will be screened between 12+0 and 29+6 weeks of gestation confirmed by ultrasound. HCV RNA level to confirm the patient has active infection will be obtained. Laboratory evaluation of liver function will be obtained, to evaluate for renal insufficiency, decompensated cirrhosis and baseline elevations of lipase and creatine kinase. Hepatitis B virus (HBV) antigen will be performed to look for evidence of active HBV infection. Medical history and demographic information will also be collected at screening. If the inclusion and exclusion criteria are met, the patient will be enrolled into the study between 20+0 and 30+0 weeks' gestation and initiate a 12-week course of a fixed-dose combination tablet of sofosbuvir 400 mg and velpatasvir 100 mg. Maternal participants will take one SOF/VEL tablet once daily for 12 weeks (84 days). The study will be completed in 8 or 9 visits (6 maternal visits and 3 infant visits). The primary endpoints are 1) maternal HCV RNA PCR 12 weeks after completion of SOF/VEL treatment (HCV RNA PCR below the lower limit of quantification will be considered evidence of SVR12) and 2) preterm delivery (spontaneous and iatrogenic) prior to 37 weeks' gestation. The secondary endpoints are 1) Maternal safety defined as maternal adverse events and pregnancy and delivery outcomes (stillbirth or intrauterine fetal demise, intrapartum hemorrhage, postpartum hemorrhage, hypertensive disorders of pregnancy, gestational diabetes, intrauterine growth restriction, cholestasis of pregnancy, severe maternal morbidity (defined by CDC), maternal admission to the intensive care unit, maternal death), 2) composite neonatal/Infant safety endpoints defined as severe neonatal morbidity with admission to neonatal intensive care unit and stratified by perinatal preterm (<37 weeks) (including fetal or neonatal death, severe bronchopulmonary dysplasia (grade 3) intraventricular hemorrhage grades III-IV, necrotizing enterocolitis (proven - Bell Stage 2A or greater), periventricular leukomalacia, retinopathy of prematurity stage III-V, or proven sepsis (early or late)) and perinatal term (>= 37 weeks) (including fetal or neonatal death, respiratory support , Apgar score ≤ 3 at 5 minutes, hypoxic ischemic encephalopathy, seizure, infection (sepsis or pneumonia), birth trauma, meconium aspiration syndrome, intracranial or subgaleal hemorrhage, or hypotension requiring vasopressor support). Other secondary endpoints are admission to the neonatal intensive care unit, neonatal death, major malformations, defined as structural abnormalities with medical, surgical or cosmetic importance, weight, length, and head circumference at birth (by exam or chart review), 8 weeks, six months and 12 months, neurodevelopmental assessments at 6 months and 12 months by Ages & Stages Questionnaires®, and infant HCV RNA PCR viral load at 8 weeks, 6 months and 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Catherine Chappell, MD, MSc; Phone Number: 412-641-1403; Email: chappellca@upmc.edu
• Study Contact Backup: Name: Leslie Meyn, PhD; Phone Number: 412-641-4233; Email: meynla@mwri.magee.edu

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • Victoria Hospital, London Health Sciences Center
      • Contact: Genevieve Eastabrook, MD; Phone Number: 519-646-6106; Email: genevieve.eastabrook@lhsc.on.ca
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital, University Health Network
      • Contact: Mia Biondi, PhD, NP-PHC; Phone Number: 647-628-6461; Email: mia.biondi@mail.mcgill.ca
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • University Health Toronto, St Michaels Hospital
      • Contact: Mark Yudin, MD; Phone Number: 43075 416-864-6060; Email: mark.yudin@unityhealth.to
• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Christ Hospital
      • Contact: John Cafardi, MD; Email: john.cafardi@thechristhospital.com
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center
      • Contact: Kara Rood, MD; Email: kara.rood@osumc.edu
      • Contact: Melanie L Paglione, MCR, BSN; Phone Number: 614-685-5550; Email: melanie.paglione@osumc.edu
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh, Magee Womens Hospital
      • Contact: Catherine Chappell, MD; Phone Number: 412-641-4242; Email: chappellca@upmc.edu
      • Contact: Ingrid Macio; Phone Number: 412-641-4242
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
      • Contact: Marcela Smid, MD; Email: marcela.smid@hsc.utah.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 through 45 years (inclusive) at screening
2. Able and willing to provide written informed consent and take part in the study procedures
3. Able and willing to provide adequate locator information, defined as at least two other alternate contacts
4. HCV antibody seropositivity with detectable HCV RNA viral load at screening
5. Chronic HCV infection of at least 6 months by laboratory report or participant reported medical history as determined by the site PI, or if duration of HCV cannot be determined then the participant can be enrolled if there is no clinical evidence of acute hepatitis C infection (defined by CDC as presence of jaundice or total bilirubin >/= 3.0 mg/dL or ALT >200IU/L)
6. Singleton pregnancy at 20 + 0 to 30 + 0 weeks' gestation at enrollment with gestational dating confirmed by ultrasound
7. Having a comprehensive anatomy scan with no evidence of major structural abnormalities as defined by the CDC birth surveillance toolkit (https://www.cdc.gov/ncbddd/birthdefects/surveillancemanual/chapters/chapter-4/chapter4-1.html) or an anomaly that would significantly impact delivery timing or neonatal outcomes as determined by the Protocol Safety Review Team (PSRT) prior to enrollment
8. Documented negative Hepatitis B testing for current infection (negative HBsAg test) prior to enrollment
9. If living with HIV, must be on antiretroviral therapy with HIV viral load <50 copies/mL on the most recent HIV viral load test within 30 days before enrollment and agree to continue antiretroviral therapy throughout study participation
10. If taking acid-suppressant medication(s), willing and able to either discontinue administration during the 12-week period of study treatment or to follow specific dosing instructions for concomitant use with SOF/VEL
11. Per participant report at screening and enrollment, agrees not to participate in other research studies involving investigational medications or investigational medical devices for the duration of study participation (does not include duration of infant participation). Note: maternal participants can participate in research studies that include standard of care medications.

Exclusion Criteria:

1. Participant report of any of the following at screening or enrollment:

   1. Previous DAA treatment for HCV (prior interferon-based treatment is acceptable) without documentation of SVR12 (HCV RNA below the lower limit of quantification at least 24 weeks after DAA initiation)
   2. Use of any medications contraindicated with concurrent use of velpatasvir or sofosbuvir according to the most current EPCLUSA® package insert30
   3. Plans to relocate away from the study site area in the next 16 months and unable/unwilling to return for study visits
   4. History of cirrhosis documented or reported by previous liver biopsy, imaging tests or on at least 2 noninvasive laboratory tests of fibrosis, including compensated cirrhosis
2. Reports participating in any other research study involving investigational medications or investigational medical devices within 60 days or less prior to enrollment (does not include research studies involving standard of care medications)
3. Known fetal chromosomal abnormality prior to enrollment (confirmed by chorionic villus sampling or amniocentesis)
4. Clinically significant and habitual non-therapeutic drug use, not including marijuana, as determined by site PI at screening and enrollment
5. At screening and enrollment, as determined by site PI, any significant, uncontrolled, active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease other than HCV (or HIV as outlined in eligibility criteria)

6. Any of the following laboratory abnormalities at screening:

   1. Aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 10 times the upper limit of normal
   2. Hemoglobin less than 9 g/dL
   3. Platelet count less than 90,000 per mm3
   4. International normalized ratio (INR) > 1.5
   5. Creatinine greater than 1.4
7. If living with HIV, CD4 count less than 200 cells/mm3 within 6 months of enrollment.
8. Any other condition that, in the opinion of the site PI/designee, would preclude appropriate informed consent, make study participation 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: Sofosbuvir/Velpatasvir; Sofosbuvir/Velpatasvir 400 MG-100 MG Oral Tablet, one tablet taken once daily for 84 days	Drug: Sofosbuvir/Velpatasvir 400 MG-100 MG Oral Tablet; One Sofosbuvir/Velpatasvir 400 MG-100 MG Oral Tablet taken once daily for 84 days.; Other Names: Epclusa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of maternal participants with sustained virologic response after completion of SOF/VEL treatment (SVR12)	Number of maternal participants with plasma level of HCV RNA PCR that is below the lower limit of quantification after completion of SOF/VEL treatment	Approximately 12 weeks
Number of maternal participants that deliver prior to 37 weeks' gestation	Number of maternal participants that deliver (spontaneous and iatrogenic) prior to 37 weeks' gestation	Approximately 28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of maternal participants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir	Number of maternal participants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir by a study physician	Approximately six months
Number of infants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir	Number of infant participants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir by a study physician	Approximately six months
Number of maternal participants whose pregnancy results in a stillbirth or intrauterine fetal demise	Number of maternal participants whose pregnancy results in a stillbirth or intrauterine fetal demise	Approximately 28 weeks
Number of maternal participants that experience intrapartum hemorrhage	Number of maternal participants that experience intrapartum hemorrhage	Approximately 28 weeks
Number of maternal participants that experience postpartum hemorrhage	Number of maternal participants that experience postpartum hemorrhage	Approximately 28 weeks
Number of maternal participants that experience a hypertensive disorder of pregnancy	Number of maternal participants that experience a hypertensive disorder of pregnancy (gestational hypertension, pre-eclampsia with and without severe features, eclampsia)	Approximately 28 weeks
Number of maternal participants that develop gestational diabetes	Number of maternal participants that develop gestational diabetes	Approximately 28 weeks
Number of maternal participants that experience cholestasis of pregnancy	Number of maternal participants that experience cholestasis of pregnancy	Approximately 28 weeks
Number of maternal participants that experience intrauterine growth restriction	Number of maternal participants that experience intrauterine growth restriction	Approximately 28 weeks
Number of maternal participants that develop severe maternal morbidity	Number of maternal participants that develop severe maternal morbidity, as defined by the Centers for Disease Control	Approximately 28 weeks
Number of maternal participants that are admitted to the intensive care unit	Number of maternal participants that are admitted to the intensive care unit	Approximately 28 weeks
Number of maternal deaths	Number of maternal deaths	Approximately 28 weeks
Number of preterm neonates (<37 weeks) admitted to the neonatal intensive care unit for severe neonatal morbidity	Perinatal preterm (<37 weeks) composite outcome defined as fetal or neonatal death, or admission to the neonatal intensive care unit for severe bronchopulmonary dysplasia (grade 3), intraventricular hemorrhage grades III-IV, necrotizing enterocolitis (proven - Bell Stage 2A or greater), periventricular leukomalacia, retinopathy of prematurity stage III-V, or proven sepsis (early or late)	Approximately 4 weeks
Number of term neonates (>=37 weeks) admitted to the neonatal intensive care unit for severe neonatal morbidity	Perinatal term (<37 weeks) composite outcome defined as fetal or neonatal death, or admission to the neonatal intensive care unit for respiratory support, Apgar score ≤ 3 at 5 minutes, hypoxic ischemic encephalopathy, seizure, infection (sepsis or pneumonia), birth trauma, meconium aspiration syndrome, intracranial or subgaleal hemorrhage, or hypotension requiring vasopressor support	Approximately 4 weeks
Number of neonates admitted to the neonatal intensive care unit	Number of neonates admitted to the neonatal intensive care unit	Approximately 4 weeks
Number of neonatal deaths	Number of neonatal deaths	Approximately 4 weeks
Number of neonates with major malformations	Number of neonates with major malformations, defined as structural abnormalities with medical, surgical or cosmetic importance.	Approximately 4 weeks
Weight of infant participant at 8 Weeks	Weight of infant participant measured at 8 weeks (by exam or chart review)	Approximately 8 weeks
Weight of infant participant at 6 months	Weight of infant participant measured at 6 months (by exam or chart review)	Approximately 6 months
Weight of infant participant at 12 months	Weight of infant participant measured at 12 months (by exam or chart review)	Approximately 12 months
Length of infant participant at 8 weeks	Length of infant participant measured at 8 weeks (by exam or chart review)	Approximately 8 weeks
Length of infant participant at 6 months	Length of infant participant measured at 6 months (by exam or chart review)	Approximately 6 months
Length of infant participant at 12 months	Length of infant participant measured at 12 months (by exam or chart review)	Approximately 12 months
Head circumference of infant participant at 8 weeks	Head circumference of infant participant measured at 8 weeks (by exam or chart review)	Approximately 8 weeks
Head circumference of infant participant at 6 months	Head circumference of infant participant measured at 6 months (by exam or chart review)	Approximately 6 months
Head circumference of infant participant at 12 months	Head circumference of infant participant measured at 12 months (by exam or chart review)	Approximately 12 months
Number of Infant Participants with Any Neurological Development Score Less than 6 at 6 months	Number of infant participants with a Bayley's score of less than 6 on either cognitive, motor or language development assessments evaluated at 6 months; Bayley's score ranges from 1 (extremely low) to 19 (very superior)	Approximately 6 months
Number of Infant Participants with Any Neurological Development Score Less than 6 at 12 months	Number of infant participants with a Bayley's score of less than 6 on either cognitive, motor or language development assessments evaluated at 12 months; Bayley's score ranges from 1 (extremely low) to 19 (very superior)	Approximately 12 months
Number of infant participants with with plasma level of HCV RNA PCR viral load that is below the lower limit of quantification at 8 weeks	Number of infant participants with with plasma level of HCV RNA PCR viral load that is below the lower limit of quantification at 8 weeks	Approximately 8 weeks
Number of infant participants with with plasma level of HCV RNA PCR viral load that is below the lower limit of quantification at 6 months	Number of infant participants with with plasma level of HCV RNA PCR viral load that is below the lower limit of quantification at 6 months	Approximately 6 months
Number of infant participants with with plasma level of HCV RNA PCR viral load that is below the lower limit of quantification at 12 months	Number of infant participants with with plasma level of HCV RNA PCR viral load that is below the lower limit of quantification at 12 months	Approximately 12 months

Collaborators and Investigators

• Sponsor: Catherine Anne Chappell
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Catherine Chappell, MD, MSc, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 18, 2021
• First Posted (Actual): December 2, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Pregnancy Complications; Chronic Disease; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Pregnancy Complications, Infectious; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir
• Other Study ID Numbers: STUDY21080043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The protocol will be published with the primary manuscript. Other data inquires can be made by e-mailing the PI at the address below after the primary manuscript has been published for 5 years time.
• IPD Sharing Time Frame: Immediately after the primary manuscript for the study is published for five years.
• IPD Sharing Access Criteria: Data requests submitted by email will be reviewed by the Principal Investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No