Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir

Sponsor

Catherine Chappell (Other)

Overall Status

Recruiting

CT.gov ID

NCT04382404

Collaborator

Gilead Sciences (Industry), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Enrollment

Location

Arm

38.2

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A single-arm, single-center, open label Phase 1 study of a 12-week course of Sofosbuvir (SOF)/Velpatasvir (VEL) in 10 HCV-infected pregnant women 1 that will evaluate the plasma pharmacokinetic parameters of SOF/VEL administered during pregnancy and compare them to those of a historical cohort of nonpregnant women.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Sofosbuvir-Velpatasvir Drug Combination	Phase 1

Detailed Description

A single-arm, single-center, open label Phase 1 study of a 12-week course of SOF/VEL in 10 HCV-infected pregnant women. Treatment will be initiated during the second trimester, reducing the risk of SOF/VEL exposure during organogenesis and ensuring treatment completion by delivery, minimizing the risk of perinatal transmission. The study will be completed in 10 or 11 visits (7 maternal visits, delivery visit and 3 infant visits) which should align with prenatal and postpartum visits. Patients will be screened between 14+0 and 22+6 weeks of gestation confirmed by ultrasound by the time of their enrollment visit who are known to have chronic HCV infection. An HCV RNA level to confirm the patient is actively infected with HCV as well as an HCV genotype will be obtained. A full laboratory evaluation of liver function will be obtained to evaluate for renal failure and decompensated cirrhosis. A Hepatitis B Virus (HBV) panel will be performed to test all patients for evidence of current or prior HBV infection before initiation of HCV treatment. If the inclusion and exclusion criteria are met, the patient will be enrolled into the study between 23+0 and 25+6 weeks' gestation and initiated on a 12 week course of SOF/VEL. Systemic exposure of both VEL and SOF (SOF and inactive metabolite GS-331007) and intracellular SOF (GS-461203) will be assessed by pharmacokinetic sampling at 3, 6, and 9 weeks after first dose. HCV RNA viral load will be assessed at 12 weeks after completion of SOF/VEL treatment. Pregnancy and delivery outcomes will be collected prospectively. Neonatal outcomes will be assessed at birth, 8 weeks, 6 months and 12 months. HCV RNA viral load will be obtained at birth (as available), 1 to 3 months, at 6 months and then again at 12 months only if negative viral loads are not documented at 1 to 3 and 6 months. Neurodevelopmental assessments will be obtained at 6 months and 12 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open-label, single armOpen-label, single arm

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1 Pharmacokinetic Trial of Sofosbuvir/Velpatasvir in Pregnant Women With Chronic Hepatitis C Virus Infection

Actual Study Start Date :

Oct 22, 2020

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sofosbuvir-Velpatasvir Sofosbuvir-Velpatasvir	Drug: Sofosbuvir-Velpatasvir Drug Combination One pill once a day for 12 weeks Other Names: Epclusa

Arm

Intervention/Treatment

Experimental: Sofosbuvir-Velpatasvir

Sofosbuvir-Velpatasvir

Drug: Sofosbuvir-Velpatasvir Drug Combination

One pill once a day for 12 weeks

Other Names:

Epclusa

Outcome Measures

Primary Outcome Measures

Maximum Concentration of Velpatasvir in Plasma [Approximately 3 months]
Maximum concentration of Velpatasvir measured in plasma samples
Maximum Concentration of Sofosbuvir in Plasma [Approximately 3 months]
Maximum concentration of Sofosbuvir measured in plasma samples
Maximum Concentration of GS-331007 in Plasma [Approximately 3 months]
Maximum concentration of GS-331007, an inactive metabolite of Sofosbuvir, measured in plasma samples
Area Under the Plasma Concentration Versus Time Curve of Velpatasvir [Approximately 3 months]
Area under the plasma concentration versus time curve of Velpatasvir
Area Under the Plasma Concentration Versus Time Curve of Sofosbuvir [Approximately 3 months]
Area under the plasma concentration versus time curve of Sofosbuvir
Area Under the Plasma Concentration Versus Time Curve of GS-331007 [Approximately 3 months]
Area under the plasma concentration versus time curve of GS-331007, an inactive metabolite of Sofosbuvir

Secondary Outcome Measures

Intracellular Concentration of GS-461203 from Peripheral Blood Mononuclear Cells [Approximately 3 months]
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from peripheral blood mononuclear cells
Intracellular Concentration of GS-461203 from Dried Blood Spots [Approximately 3 months]
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried blood spots
Percentage of Unbound Velpatasvir measured in Plasma [Approximately 3 months]
Percentage of unbound Velpatasvir out of total Velpatasvir, unbound and protein-bound, measured in plasma
Percentage of Unbound Sofosbuvir measured in Plasma [Approximately 3 months]
Percentage of unbound Sofosbuvir out of total Sofosbuvir, unbound and protein-bound, measured in plasma
Quantity of Hepatitis C Virus in Plasma After Completion of Velpatasvir and Sofosbuvir Treatment [Approximately 6 months]
Quantity of Hepatitis C RNA measured in plasma measured after completion of Velpatasvir and Sofosbuvir treatment regimen
Number of Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir [Approximately 6 months]
Number of maternal and infant participants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir by a study physician
Gestational Age at Delivery [Approximately 6 months]
Gestational age at delivery determined by medical record review
Infant Weight at Delivery [Approximately 6 months]
Infant birth weight determined by medical record review
Frequency of Delivery Modes [Approximately 6 months]
Frequency of delivery modes (spontaneous vaginal, assisted vaginal, cesarean section) determined by medical record review
Number of Infant Participants with Congenital Anomalies [Approximately 6 months]
Number of infant participants with congenital anomalies determined by medical record review
-Weight of Infant Participant [Approximately 12 months]
Weight of infant participant measured at 1-3 months, 6 months, and 12 months
Length of Infant Participant [Approximately 12 months]
Length of infant participant measured at 1-3 months, 6 months, and 12 months
Head Circumference of Infant Participant [Approximately 12 months]
Head circumference of infant participant measured at 1-3 months, 6 months, and 12 months
Quantity of Hepatitis C Virus in Infant Plasma [Approximately 12 months]
-Quantity of Hepatitis C viral RNA measured in infant plasma will be assessed at birth, 1-3 months, 6 months, and 12 months
Number of Infant Participants Referred for Early Neurological Development Intervention [Approximately 12 months]
Number of infant participants referred for early intervention based on neurological development assessments (Bayley's scores)
Number of Infant Participants with Any Neurological Development Score Less than 6 [Approximately 12 months]
Number of infant participants with a Bayley's score of less than 6 on either cognitive, motor or language development assessments; Bayley's score ranges from 1 (extremely low) to 19 (very superior)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 39 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Able and willing to provide written informed consent and take part in the study -procedures
Able and willing to provide adequate locator information
Chronic hepatitis C viral (HCV) infection, defined as a positive HCV test at least 6 months prior to screening
Detectable HCV RNA viral load at Screening
Desired pregnancy at 23 + 0 to 25 + 6 weeks' gestation at enrollment with gestational dating confirmed by ultrasound
Singleton gestation with no known fetal abnormalities
Documented negative Hepatitis B (HB) testing for current infection (negative HB serum antigen test) or previous infection (negative anti-HB Core) performed at the screening visit
Negative HIV testing at the screening visit
Per participant report at screening and enrollment, agrees not to participate in other research studies involving drugs or medical devices for the duration of study participation

Exclusion Criteria:

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

Previous treatment for Hepatitis C virus with sofosbuvir or a non-structural protein 5A inhibitor
Use of any medications contraindicated with concurrent use of velpatasvir or sofosbuvir according to the most current Epclusa package insert
Plans to relocate away from the study site area in the next 1 year and 4 months and unable/unwilling to return for study visits
Current sexual partner is known to be infected with HIV or Hepatitis B virus
History of cirrhosis documented or reported by previous liver biopsy or liver imaging tests

Reports participating in any other research study involving drugs or medical devices within 60 days or less prior to enrollment
Clinically significant and habitual non-therapeutic drug abuse, not including marijuana, as determined by Protocol Chair
At Screening or Enrollment, as determined by the Protocol Chair, any significant uncontrolled active or chronic cardiovascular, renal, liver (such as evidence of decompensated cirrhosis by ascites, encephalopathy, or variceal hemorrhage), hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease (other than Hepatitis C)
Has a high risk of preterm birth defined as a history of spontaneous preterm birth at less than 34 weeks of gestation or a shortened cervical length of less than 20 millimeters
Has any of the following laboratory abnormalities at screening:

Aspartate aminotransferase or alanine transaminase greater than 10 times the upper limited of normal
Hemoglobin less than 9g/dL
Platelet count less than 90,000 per mm3
International normalized ratio > 1.5
Creatinine greater than 1.4

Has any other condition that, in the opinion of the investigator or designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives