Hepatitis C, ChronicPhase 1NCT04382404
Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir
A Phase 1 study testing Sofosbuvir-Velpatasvir Drug Combination in people with Hepatitis C, Chronic, run by Catherine Anne Chappell at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women only
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- Sofosbuvir-Velpatasvir Drug Combination
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2020to 16 Oct 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh, Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
About this study
Official title: 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.
Read the 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.
- Conditions
- Hepatitis C, Chronic
- Being tested
- Sofosbuvir-Velpatasvir Drug Combination
- Keywords
- pregnancy
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sofosbuvir-Velpatasvir Drug CombinationDrug
Also called Epclusa
One oral pill containing 400mg sofosbuvir and 100mg velpatasvir taken once daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sofosbuvir-Velpatasvir | Experimental | Sofosbuvir-Velpatasvir Receives: Drug: Sofosbuvir-Velpatasvir Drug Combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Concentration of Velpatasvir in Maternal Plasma
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.
Measured: Up to 9 weeks from initiation of treatment
Maximum Concentration of Sofosbuvir in Maternal Plasma
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.
Measured: Up to 9-weeks from initiation of treatment
Maximum Concentration of GS-331007 in Maternal Plasma
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.
Measured: Up to 9 weeks from initiation of treatment
Area Under the Maternal Plasma Concentration Versus Time Curve of Velpatasvir
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.
Measured: Up to 9 weeks from initiation of treatment
Area Under the Maternal Plasma Concentration Versus Time Curve of Sofosbuvir
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.
Measured: Up to 9 weeks from initiation of treatment
Area Under the Maternal Plasma Concentration Versus Time Curve of GS-331007
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.
Measured: Up to 9 weeks from initiation of treatment
Secondary outcomes (28)
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 3 Weeks
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from maternal peripheral blood mononuclear cells measured 3 weeks after initiation of treatment
Measured: Approximately 3 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 6 Weeks
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from maternal peripheral blood mononuclear cells measured 6 weeks after initiation of treatment
Measured: Approximately 6 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 9 Weeks
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from maternal peripheral blood mononuclear cells measured 9 weeks after initiation of treatment
Measured: Approximately 9 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 3 Weeks
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried maternal blood spots measured 3 weeks after initiation of treatment
Measured: Approximately 3 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 6 Weeks
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried maternal blood spots measured 6 weeks after initiation of treatment
Measured: Approximately 6 weeks from initiation of treatment
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 9 Weeks
Intracellular concentration of GS-461203, the active form of Sofosbuvir, from dried maternal blood spots measured 9 weeks after initiation of treatment
Measured: Approximately 9 weeks from initiation of treatment
Quantity of Hepatitis C Virus in Maternal Plasma After Completion of Velpatasvir and Sofosbuvir Treatment
Quantity of Hepatitis C RNA in maternal plasma measured at least 12 weeks after completion of Velpatasvir and Sofosbuvir treatment regimen
Measured: Approximately 24 weeks from initiation of treatment
Number of Maternal and Infant Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir
Number of maternal and infant participants that experience an adverse event that is deemed related to Sofosbuvir/Velpatasvir by a study physician
Measured: Up to 16 weeks from initiation of treatment or 12 months from delivery
Maternal Gestational Age at Delivery
Maternal gestational age at delivery determined by medical record review
Measured: Up to 16 weeks from treatment initiation (at delivery)
Infant Weight at Delivery
Infant birth weight determined by medical record review
Measured: Up to 16 weeks from treatment initiation (at delivery)
Frequency of Delivery Modes for Maternal Participants
Frequency of delivery modes (spontaneous and assisted vaginal, scheduled and emergent cesarean section) for maternal participants determined by medical record review
Measured: Up to 16 weeks from treatment initiation (at delivery)
Number of Infant Participants With Congenital Anomalies
Number of infant participants with congenital anomalies determined by medical record review for up to 12 months of age.
Measured: Up to 12 months from delivery
Weight of Infant Participant at 1 to 3 Months
Weight of infant participant measured at 1 to 3 months of age
Measured: Approximately 3 months from delivery
Weight of Infant Participant at 6 Months
Weight of infant participant measured at 6 months of age
Measured: Approximately 6 months from delivery
Weight of Infant Participant at 12 Months
Weight of infant participant measured at 12 months of age
Measured: Approximately 12 months from delivery
Length of Infant Participant at 1 to 3 Months
Length of infant participant measured at 1 to 3 months of age
Measured: Approximately 3 months from delivery
Length of Infant Participant at 6 Months
Length of infant participant measured at 6 months of age
Measured: Approximately 6 months from delivery
Length of Infant Participant at 12 Months
Length of infant participant measured at 12 months of age
Measured: Approximately 12 months from delivery
Head Circumference of Infant Participant at 1 to 3 Months
Head circumference of infant participant measured at 1 to 3 months of age
Measured: Approximately 3 months from delivery
Head Circumference of Infant Participant at 6 Months
Head circumference of infant participant measured at 6 months of age
Measured: Approximately 6 months from delivery
Head Circumference of Infant Participant at 12 Months
Head circumference of infant participant measured at 12 months of age
Measured: Approximately 12 months from delivery
Quantity of Hepatitis C Virus in Infant Plasma at Birth
Quantity of Hepatitis C viral RNA measured in infant plasma assessed at birth
Measured: Up to 16 weeks from treatment initiation (at delivery)
Quantity of Hepatitis C Virus in Infant Plasma at 1 to 3 Months
Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 1 to 3 months of age
Measured: Approximately 3 months from delivery
Quantity of Hepatitis C Virus in Infant Plasma at 6 Months
Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 6 months of age
Measured: Approximately 6 months from delivery
Quantity of Hepatitis C Virus in Infant Plasma at 12 Months
Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 12 months of age
Measured: Approximately 12 months from delivery
Number of Infant Participants Referred for Early Neurological Development Intervention
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)
Measured: Approximately 12 months from delivery
Percentage of Unbound Sofosbuvir Measured in Maternal Plasma
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.
Measured: Approximately 9 weeks from initiation of maternal treatment
Percentage of Unbound Velpatasvir Measured in Maternal Plasma
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.
Measured: Approximately 9 weeks from initiation of maternal treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2020
- Study start22 Oct 2020
- Primary completion16 Oct 2023
- Study completion16 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label, single arm
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Anne Chappell
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Catherine Anne Chappell, University of Pittsburgh
- Investigators
- Catherine Chappell, MD, MSc, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04382404
- Sponsor's protocol ID
- STUDY19100377
- Other IDs
- R21HD101996
- Status last verified
- Dec 2024
- First submitted
- 16 Feb 2020
- Last updated
- 1 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data requests can be submitted by email to the Principal Investigator
Publications
Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; Hughes BL, Page CM, Kuller JA. Hepatitis C in pregnancy: screening, treatment, and management. Am J Obstet Gynecol. 2017 Nov;217(5):B2-B12. doi: 10.1016/j.ajog.2017.07.039. Epub 2017 Aug 4.
PubMed 28782502Gilbert EM, Darin KM, Scarsi KK, McLaughlin MM. Antiretroviral Pharmacokinetics in Pregnant Women. Pharmacotherapy. 2015 Sep;35(9):838-55. doi: 10.1002/phar.1626. Epub 2015 Aug 21.
PubMed 26297552Chappell CA, Krans EE, Bunge KE, Macio IS, Bogen D, Scarsi KK, Meyn LA, Hillier SL. A Phase 1 Study of Ledipasvir/Sofosbuvir in Pregnant Women with Hepatitis C Virus. In: Conferences on Retroviruses and Opportunistic Infections; 2010 Mar 4-7; Seattle, WA; Abstract 87
Ward RM, Varner MW. Principles of Pharmacokinetics in the Pregnant Woman and Fetus. Clin Perinatol. 2019 Jun;46(2):383-398. doi: 10.1016/j.clp.2019.02.014. Epub 2019 Mar 30.
PubMed 31010566MacBrayne CE, Kiser JJ. Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV. Clin Infect Dis. 2016 Jul 15;63 Suppl 1(Suppl 1):S12-23. doi: 10.1093/cid/ciw220.
PubMed 27363437Kirby BJ, Symonds WT, Kearney BP, Mathias AA. Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir. Clin Pharmacokinet. 2015 Jul;54(7):677-90. doi: 10.1007/s40262-015-0261-7.
PubMed 25822283Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16.
PubMed 26571066Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.
PubMed 26575258
Study at a glance
From the registry record, last updated by the sponsor on 1 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Pharmacokinetic Trial of Sofosbuvir/Velpatasvir in Pregnant Women With Chronic Hepatitis C Virus Infection
- ClinicalTrials.gov ID
- NCT04382404
- Acronym / sponsor ID
- STUDY19100377
- Conditions
- Hepatitis C, Chronic
- Keywords
- pregnancy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Catherine Anne ChappellUniversity, hospital or other
- Collaborators
- Gilead Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 22 Oct 2020 (actual)
- Primary completion
- 16 Oct 2023 (actual)
- Study completion
- 16 Oct 2023 (actual)
- First posted
- 11 May 2020 (actual)
- Results
- Posted 1 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label, single arm
| Arm | Type | Receives |
|---|---|---|
| Sofosbuvir-Velpatasvir | Experimental | Drug: Sofosbuvir-Velpatasvir Drug CombinationSofosbuvir-Velpatasvir |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (17 listed)
- Participant report of any of the following at screening or enrollment:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sofosbuvir-Velpatasvir Drug CombinationAlso: EpclusaOne oral pill containing 400mg sofosbuvir and 100mg velpatasvir taken once daily for 12 weeks | Drug | Sofosbuvir-Velpatasvir |
Primary outcome
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.
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.
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.
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.
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.
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.
28 secondary outcomes
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 From Maternal Peripheral Blood Mononuclear Cells at 6 Weeks
Time frame: 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 From Dried Maternal Blood Spots at 3 Weeks
Time frame: 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 From Dried Maternal Blood Spots at 9 Weeks
Time frame: 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
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
Maternal Gestational Age at Delivery
Time frame: Up to 16 weeks from treatment initiation (at delivery)
Infant Weight at Delivery
Time frame: 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)
Number of Infant Participants With Congenital Anomalies
Time frame: 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 at 6 Months
Time frame: Approximately 6 months from delivery
Weight of Infant Participant at 12 Months
Time frame: 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 at 6 Months
Time frame: Approximately 6 months from delivery
Length of Infant Participant at 12 Months
Time frame: 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 at 6 Months
Time frame: Approximately 6 months from delivery
Head Circumference of Infant Participant at 12 Months
Time frame: 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 Virus in Infant Plasma at 1 to 3 Months
Time frame: 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 Virus in Infant Plasma at 12 Months
Time frame: Approximately 12 months from delivery
Number of Infant Participants Referred for Early Neurological Development Intervention
Time frame: 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 Unbound Velpatasvir Measured in Maternal Plasma
Time frame: Approximately 9 weeks from initiation of maternal treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28782502Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; Hughes BL, Page CM, Kuller JA. Hepatitis C in pregnancy: screening, treatment, and management. Am J Obstet Gynecol. 2017 Nov;217(5):B2-B12. doi: 10.1016/j.ajog.2017.07.039. Epub 2017 Aug 4.
- Background: PubMed 26297552Gilbert EM, Darin KM, Scarsi KK, McLaughlin MM. Antiretroviral Pharmacokinetics in Pregnant Women. Pharmacotherapy. 2015 Sep;35(9):838-55. doi: 10.1002/phar.1626. Epub 2015 Aug 21.
- BackgroundChappell CA, Krans EE, Bunge KE, Macio IS, Bogen D, Scarsi KK, Meyn LA, Hillier SL. A Phase 1 Study of Ledipasvir/Sofosbuvir in Pregnant Women with Hepatitis C Virus. In: Conferences on Retroviruses and Opportunistic Infections; 2010 Mar 4-7; Seattle, WA; Abstract 87
- Background: PubMed 31010566Ward RM, Varner MW. Principles of Pharmacokinetics in the Pregnant Woman and Fetus. Clin Perinatol. 2019 Jun;46(2):383-398. doi: 10.1016/j.clp.2019.02.014. Epub 2019 Mar 30.
- Background: PubMed 27363437MacBrayne CE, Kiser JJ. Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV. Clin Infect Dis. 2016 Jul 15;63 Suppl 1(Suppl 1):S12-23. doi: 10.1093/cid/ciw220.
- Background: PubMed 25822283Kirby BJ, Symonds WT, Kearney BP, Mathias AA. Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir. Clin Pharmacokinet. 2015 Jul;54(7):677-90. doi: 10.1007/s40262-015-0261-7.
- Background: PubMed 26571066Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16.
- Background: PubMed 26575258Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.
- Food and Drug Administration. Epclusa Package Insert.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data requests can be submitted by email to the Principal Investigator
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine Chappell, MD, MSc principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sofosbuvir-Velpatasvir Drug Combination in people with Hepatitis C, Chronic, run by Catherine Anne Chappell at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Concentration of Velpatasvir in Maternal Plasma (time frame: Up to 9 weeks from initiation of treatment). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04382404, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jan 2025.