Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir

December 4, 2024 updated by: Catherine Anne Chappell

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh, Magee Womens Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 39 years (Adult)

Accepts Healthy Volunteers

No

Description

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:

    1. Previous treatment for Hepatitis C virus with sofosbuvir or a non-structural protein 5A inhibitor
    2. Use of any medications contraindicated with concurrent use of velpatasvir or sofosbuvir according to the most current Epclusa package insert
    3. 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
    4. Current sexual partner is known to be infected with HIV or Hepatitis B virus
    5. 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:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sofosbuvir-Velpatasvir
Drug: Sofosbuvir-Velpatasvir Drug Combination
One oral pill containing 400mg sofosbuvir and 100mg velpatasvir taken once daily for 12 weeks
Other Names:
  • Epclusa

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Concentration of Velpatasvir in Maternal Plasma
Time Frame: Up to 9 weeks from initiation of treatment
Maximum concentration of Velpatasvir measured in maternal plasma samples. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation. At the 6-week visit, a single convenience blood sample was collected.
Up to 9 weeks from initiation of treatment
Maximum Concentration of Sofosbuvir in Maternal Plasma
Time Frame: Up to 9-weeks from initiation of treatment
Maximum concentration of Sofosbuvir measured in maternal plasma samples. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation. At the 6-week visit, a single convenience blood sample was collected.
Up to 9-weeks from initiation of treatment
Maximum Concentration of GS-331007 in Maternal Plasma
Time Frame: Up to 9 weeks from initiation of treatment
Maximum concentration of GS-331007, an inactive metabolite of Sofosbuvir, measured in maternal plasma samples. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation. At the 6-week visit, a single convenience blood sample was collected.
Up to 9 weeks from initiation of treatment
Area Under the Maternal Plasma Concentration Versus Time Curve of Velpatasvir
Time Frame: Up to 9 weeks from initiation of treatment
Area under the maternal plasma concentration of Velpatasvir versus time curve tau of the dosing interval. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation.
Up to 9 weeks from initiation of treatment
Area Under the Maternal Plasma Concentration Versus Time Curve of Sofosbuvir
Time Frame: Up to 9 weeks from initiation of treatment
Area under the maternal plasma concentration of Sofosbuvir versus time curve tau of the dosing interval. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation.
Up to 9 weeks from initiation of treatment
Area Under the Maternal Plasma Concentration Versus Time Curve of GS-331007
Time Frame: Up to 9 weeks from initiation of treatment
Area under the maternal plasma concentration of GS-331007 versus time curve tau of the dosing interval; GS-331007 is an inactive metabolite of Sofosbuvir. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation.
Up to 9 weeks from initiation of treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 3 Weeks
Time Frame: Approximately 3 weeks from initiation of treatment
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from maternal peripheral blood mononuclear cells measured 3 weeks after initiation of treatment
Approximately 3 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 6 Weeks
Time Frame: Approximately 6 weeks from initiation of treatment
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from maternal peripheral blood mononuclear cells measured 6 weeks after initiation of treatment
Approximately 6 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 9 Weeks
Time Frame: Approximately 9 weeks from initiation of treatment
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from maternal peripheral blood mononuclear cells measured 9 weeks after initiation of treatment
Approximately 9 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 3 Weeks
Time Frame: Approximately 3 weeks from initiation of treatment
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried maternal blood spots measured 3 weeks after initiation of treatment
Approximately 3 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 6 Weeks
Time Frame: Approximately 6 weeks from initiation of treatment
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried maternal blood spots measured 6 weeks after initiation of treatment
Approximately 6 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 9 Weeks
Time Frame: Approximately 9 weeks from initiation of treatment
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried maternal blood spots measured 9 weeks after initiation of treatment
Approximately 9 weeks from initiation of treatment
Quantity of Hepatitis C Virus in Maternal Plasma After Completion of Velpatasvir and Sofosbuvir Treatment
Time Frame: Approximately 24 weeks from initiation of treatment
Quantity of Hepatitis C RNA in maternal plasma measured at least 12 weeks after completion of Velpatasvir and Sofosbuvir treatment regimen
Approximately 24 weeks from initiation of treatment
Number of Maternal and Infant Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir
Time Frame: Up to 16 weeks from initiation of treatment or 12 months from delivery
Number of maternal and infant participants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir by a study physician
Up to 16 weeks from initiation of treatment or 12 months from delivery
Maternal Gestational Age at Delivery
Time Frame: Up to 16 weeks from treatment initiation (at delivery)
Maternal gestational age at delivery determined by medical record review
Up to 16 weeks from treatment initiation (at delivery)
Infant Weight at Delivery
Time Frame: Up to 16 weeks from treatment initiation (at delivery)
Infant birth weight determined by medical record review
Up to 16 weeks from treatment initiation (at delivery)
Frequency of Delivery Modes for Maternal Participants
Time Frame: Up to 16 weeks from treatment initiation (at delivery)
Frequency of delivery modes (spontaneous and assisted vaginal, scheduled and emergent cesarean section) for maternal participants determined by medical record review
Up to 16 weeks from treatment initiation (at delivery)
Number of Infant Participants With Congenital Anomalies
Time Frame: Up to 12 months from delivery
Number of infant participants with congenital anomalies determined by medical record review for up to 12 months of age.
Up to 12 months from delivery
Weight of Infant Participant at 1 to 3 Months
Time Frame: Approximately 3 months from delivery
Weight of infant participant measured at 1 to 3 months of age
Approximately 3 months from delivery
Weight of Infant Participant at 6 Months
Time Frame: Approximately 6 months from delivery
Weight of infant participant measured at 6 months of age
Approximately 6 months from delivery
Weight of Infant Participant at 12 Months
Time Frame: Approximately 12 months from delivery
Weight of infant participant measured at 12 months of age
Approximately 12 months from delivery
Length of Infant Participant at 1 to 3 Months
Time Frame: Approximately 3 months from delivery
Length of infant participant measured at 1 to 3 months of age
Approximately 3 months from delivery
Length of Infant Participant at 6 Months
Time Frame: Approximately 6 months from delivery
Length of infant participant measured at 6 months of age
Approximately 6 months from delivery
Length of Infant Participant at 12 Months
Time Frame: Approximately 12 months from delivery
Length of infant participant measured at 12 months of age
Approximately 12 months from delivery
Head Circumference of Infant Participant at 1 to 3 Months
Time Frame: Approximately 3 months from delivery
Head circumference of infant participant measured at 1 to 3 months of age
Approximately 3 months from delivery
Head Circumference of Infant Participant at 6 Months
Time Frame: Approximately 6 months from delivery
Head circumference of infant participant measured at 6 months of age
Approximately 6 months from delivery
Head Circumference of Infant Participant at 12 Months
Time Frame: Approximately 12 months from delivery
Head circumference of infant participant measured at 12 months of age
Approximately 12 months from delivery
Quantity of Hepatitis C Virus in Infant Plasma at Birth
Time Frame: Up to 16 weeks from treatment initiation (at delivery)
Quantity of Hepatitis C viral RNA measured in infant plasma assessed at birth
Up to 16 weeks from treatment initiation (at delivery)
Quantity of Hepatitis C Virus in Infant Plasma at 1 to 3 Months
Time Frame: Approximately 3 months from delivery
Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 1 to 3 months of age
Approximately 3 months from delivery
Quantity of Hepatitis C Virus in Infant Plasma at 6 Months
Time Frame: Approximately 6 months from delivery
Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 6 months of age
Approximately 6 months from delivery
Quantity of Hepatitis C Virus in Infant Plasma at 12 Months
Time Frame: Approximately 12 months from delivery
Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 12 months of age
Approximately 12 months from delivery
Number of Infant Participants Referred for Early Neurological Development Intervention
Time Frame: Approximately 12 months from delivery
Number of infant participants referred for early intervention based on neurological development assessments using Bayley Scales of Infant and Toddler Development. Infant participants with a Bayley's score of less than 6 on either cognitive, motor or language development assessments indicates an infant at risk for delayed development; Bayley's score ranges from 1 (extremely low) to 19 (very superior)
Approximately 12 months from delivery
Percentage of Unbound Sofosbuvir Measured in Maternal Plasma
Time Frame: Approximately 9 weeks from initiation of maternal treatment
Percentage of Sofosbuvir not bound to protein out of total protein- unbound and bound Sofosbuvir measured in maternal plasma samples. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation. At the 6-week visit, a single convenience blood sample was collected.
Approximately 9 weeks from initiation of maternal treatment
Percentage of Unbound Velpatasvir Measured in Maternal Plasma
Time Frame: Approximately 9 weeks from initiation of maternal treatment
Percentage of Velpatasvir not bound to protein out of total protein- unbound and bound Velpatasvir measured in maternal plasma samples. Plasma samples were obtained pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 5-, 8-, and 12- and 24 hours post-dose at the 3- and 9-week visits after treatment initiation. At the 6-week visit, a single convenience blood sample was collected.
Approximately 9 weeks from initiation of maternal treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Catherine Anne Chappell

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Gilead Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Catherine Chappell, MD, MSc, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 22, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 16, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 16, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 16, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 11, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY19100377
  • R21HD101996 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data requests can be submitted by email to the Principal Investigator

IPD Sharing Time Frame

Immediately after the primary manuscript for the study is published. Information will be available for an indefinite period of time.

IPD Sharing Access Criteria

Data requests submitted by email will be reviewed by the Principal Investigator on a case by case basis.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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