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CompletedNCT04382404Updated Jan 1, 2025Results posted

Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir

A Phase 1 interventional study of Sofosbuvir-Velpatasvir Drug Combination in Hepatitis C, Chronic, sponsored by Catherine Anne Chappell. Completed at 1 site in United States. Open to female participants aged 18 Years to 39 Years. Per ClinicalTrials.gov, last updated 2025-01-01.

Sponsored by Catherine Anne Chappell · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
11
Allocation
Not applicable
Ages
18 Years to 39 Years
Sex
Female
01

Study 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 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.

02

Conditions studied

  • Hepatitis C, Chronic

Keywords

  • pregnancy
03

In context

Hepatitis A

2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 11 is below the median of 100 across 1,886 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

Catherine Anne Chappell is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 39 Years
Sexes eligible
Female
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
11 participants (actual)

Study arms

  • Experimental
    Sofosbuvir-Velpatasvir

    Sofosbuvir-Velpatasvir

    Drug: Sofosbuvir-Velpatasvir Drug Combination

Interventions

  • DrugSofosbuvir-Velpatasvir Drug Combination

    One oral pill containing 400mg sofosbuvir and 100mg velpatasvir taken once daily for 12 weeks

    Also known as: Epclusa

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Up to 9 weeks from initiation of treatment

  2. 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.

    Time frame: Up to 9-weeks from initiation of treatment

  3. 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.

    Time frame: Up to 9 weeks from initiation of treatment

  4. 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.

    Time frame: Up to 9 weeks from initiation of treatment

  5. 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.

    Time frame: Up to 9 weeks from initiation of treatment

  6. 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.

    Time frame: Up to 9 weeks from initiation of treatment

Secondary outcomes

  1. 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

    Time frame: Approximately 3 weeks from initiation of treatment

  2. 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

    Time frame: Approximately 6 weeks from initiation of treatment

  3. 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

    Time frame: Approximately 9 weeks from initiation of treatment

  4. 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

    Time frame: Approximately 3 weeks from initiation of treatment

  5. 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

    Time frame: Approximately 6 weeks from initiation of treatment

  6. 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

    Time frame: Approximately 9 weeks from initiation of treatment

  7. 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

    Time frame: Approximately 24 weeks from initiation of treatment

  8. 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

    Time frame: Up to 16 weeks from initiation of treatment or 12 months from delivery

  9. Maternal Gestational Age at Delivery

    Maternal gestational age at delivery determined by medical record review

    Time frame: Up to 16 weeks from treatment initiation (at delivery)

  10. Infant Weight at Delivery

    Infant birth weight determined by medical record review

    Time frame: Up to 16 weeks from treatment initiation (at delivery)

  11. 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

    Time frame: Up to 16 weeks from treatment initiation (at delivery)

  12. 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.

    Time frame: Up to 12 months from delivery

  13. Weight of Infant Participant at 1 to 3 Months

    Weight of infant participant measured at 1 to 3 months of age

    Time frame: Approximately 3 months from delivery

  14. Weight of Infant Participant at 6 Months

    Weight of infant participant measured at 6 months of age

    Time frame: Approximately 6 months from delivery

  15. Weight of Infant Participant at 12 Months

    Weight of infant participant measured at 12 months of age

    Time frame: Approximately 12 months from delivery

  16. Length of Infant Participant at 1 to 3 Months

    Length of infant participant measured at 1 to 3 months of age

    Time frame: Approximately 3 months from delivery

  17. Length of Infant Participant at 6 Months

    Length of infant participant measured at 6 months of age

    Time frame: Approximately 6 months from delivery

  18. Length of Infant Participant at 12 Months

    Length of infant participant measured at 12 months of age

    Time frame: Approximately 12 months from delivery

  19. Head Circumference of Infant Participant at 1 to 3 Months

    Head circumference of infant participant measured at 1 to 3 months of age

    Time frame: Approximately 3 months from delivery

  20. Head Circumference of Infant Participant at 6 Months

    Head circumference of infant participant measured at 6 months of age

    Time frame: Approximately 6 months from delivery

  21. Head Circumference of Infant Participant at 12 Months

    Head circumference of infant participant measured at 12 months of age

    Time frame: Approximately 12 months from delivery

  22. Quantity of Hepatitis C Virus in Infant Plasma at Birth

    Quantity of Hepatitis C viral RNA measured in infant plasma assessed at birth

    Time frame: Up to 16 weeks from treatment initiation (at delivery)

  23. 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

    Time frame: Approximately 3 months from delivery

  24. 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

    Time frame: Approximately 6 months from delivery

  25. 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

    Time frame: Approximately 12 months from delivery

  26. 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)

    Time frame: Approximately 12 months from delivery

  27. 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.

    Time frame: Approximately 9 weeks from initiation of maternal treatment

  28. 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.

    Time frame: Approximately 9 weeks from initiation of maternal treatment

07

Results

Posted Jan 1, 2025

Participant flow

Participant flow — Overall Study
MilestoneSofosbuvir-Velpatasvir
Started11
Completed8
Not completed3
Withdrew: Adverse event1
Withdrew: Lost to follow-up2

Outcome measures

PrimaryMaximum 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.

Time frame:
Up to 9 weeks from initiation of treatment
Reported as:
Geometric mean · ng/mL
Maximum Concentration of Velpatasvir in Maternal Plasma
ng/mLSofosbuvir-Velpatasvir
Maximum Concentration of Velpatasvir in Maternal Plasma381.93 ± 38.35
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 0.85 · 90% CI 0.63 to 1.15The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
PrimaryMaximum 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.

Time frame:
Up to 9-weeks from initiation of treatment
Reported as:
Geometric mean · ng/mL
Maximum Concentration of Sofosbuvir in Maternal Plasma
ng/mLSofosbuvir-Velpatasvir
Maximum Concentration of Sofosbuvir in Maternal Plasma1455.09 ± 43.92
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 1.19 · 90% CI 0.88 to 1.60The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
PrimaryMaximum 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.

Time frame:
Up to 9 weeks from initiation of treatment
Reported as:
Geometric mean · ng/mL
Maximum Concentration of GS-331007 in Maternal Plasma
ng/mLSofosbuvir-Velpatasvir
Maximum Concentration of GS-331007 in Maternal Plasma752.66 ± 21.85
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 0.57 · 90% CI 0.49 to 0.67The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
PrimaryArea 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.

Time frame:
Up to 9 weeks from initiation of treatment
Reported as:
Geometric mean · hr*ng/mL
Area Under the Maternal Plasma Concentration Versus Time Curve of Velpatasvir
hr*ng/mLSofosbuvir-Velpatasvir
Area Under the Maternal Plasma Concentration Versus Time Curve of Velpatasvir3244.45 ± 39.89
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 0.91 · 90% CI 0.67 to 1.23The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
PrimaryArea 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.

Time frame:
Up to 9 weeks from initiation of treatment
Reported as:
Geometric mean · hr*ng/mL
Area Under the Maternal Plasma Concentration Versus Time Curve of Sofosbuvir
hr*ng/mLSofosbuvir-Velpatasvir
Area Under the Maternal Plasma Concentration Versus Time Curve of Sofosbuvir2039.62 ± 29.75
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 1.39 · 90% CI 1.06 to 1.78
PrimaryArea 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.

Time frame:
Up to 9 weeks from initiation of treatment
Reported as:
Geometric mean · hr*ng/mL
Area Under the Maternal Plasma Concentration Versus Time Curve of GS-331007
hr*ng/mLSofosbuvir-Velpatasvir
Area Under the Maternal Plasma Concentration Versus Time Curve of GS-3310079558.94 ± 18.75
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 0.62 · 90% CI 0.55 to 0.71
SecondaryIntracellular 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

Time frame:
Approximately 3 weeks from initiation of treatment
Reported as:
Geometric mean · fmol/10^6 cells
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 3 Weeks
fmol/10^6 cellsSofosbuvir-Velpatasvir
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 3 Weeks2111 (1096 to 4066)
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 1.43 · 95% CI 0.91 to 2.25
SecondaryIntracellular 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

Time frame:
Approximately 6 weeks from initiation of treatment
Reported as:
Geometric mean · fmol/10^6 cells
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 6 Weeks
fmol/10^6 cellsSofosbuvir-Velpatasvir
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 6 Weeks2808 (1559 to 5058)
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 1.91 · 95% CI 1.14 to 3.19The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
SecondaryIntracellular 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

Time frame:
Approximately 9 weeks from initiation of treatment
Reported as:
Geometric mean · fmol/10^6 cells
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 9 Weeks
fmol/10^6 cellsSofosbuvir-Velpatasvir
Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 9 Weeks2212 (1267 to 3864)
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: 1.50 · 95% CI 0.87 to 2.60The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
SecondaryIntracellular 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

Time frame:
Approximately 3 weeks from initiation of treatment
Reported as:
Geometric mean · fmol/punch
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 3 Weeks
fmol/punchSofosbuvir-Velpatasvir
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 3 Weeks340 (287 to 403)
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: .53 · 95% CI .50 to .56The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
SecondaryIntracellular 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

Time frame:
Approximately 6 weeks from initiation of treatment
Reported as:
Geometric mean · fmol/punch
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 6 Weeks
fmol/punchSofosbuvir-Velpatasvir
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 6 Weeks340 (278 to 418)
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: .53 · 95% CI .49 to .58The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
SecondaryIntracellular 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

Time frame:
Approximately 9 weeks from initiation of treatment
Reported as:
Geometric mean · fmol/punch
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 9 Weeks
fmol/punchSofosbuvir-Velpatasvir
Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 9 Weeks356 (275 to 461)
Statistical analysis
  • Sofosbuvir-Velpatasvir · Geometric mean ratio: .55 · 95% CI .48 to .64The pregnant cohort was the numerator, and the non-pregnant cohort was the denominator.
SecondaryQuantity 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

Time frame:
Approximately 24 weeks from initiation of treatment
Reported as:
Median · copies/mL
Quantity of Hepatitis C Virus in Maternal Plasma After Completion of Velpatasvir and Sofosbuvir Treatment
copies/mLSofosbuvir-Velpatasvir
Quantity of Hepatitis C Virus in Maternal Plasma After Completion of Velpatasvir and Sofosbuvir TreatmentNA (NA to NA)
SecondaryNumber 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

Time frame:
Up to 16 weeks from initiation of treatment or 12 months from delivery
Reported as:
Count of participants · Participants
Number of Maternal and Infant Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir
ParticipantsSofosbuvir-Velpatasvir - Maternal ParticipantsSofosbuvir-Velpatasvir - Infant Participants
Number of Maternal and Infant Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir90
SecondaryMaternal Gestational Age at Delivery

Maternal gestational age at delivery determined by medical record review

Time frame:
Up to 16 weeks from treatment initiation (at delivery)
Reported as:
Median · weeks
Maternal Gestational Age at Delivery
weeksSofosbuvir-Velpatasvir
Maternal Gestational Age at Delivery39.00 (35.57 to 39.43)
SecondaryInfant Weight at Delivery

Infant birth weight determined by medical record review

Time frame:
Up to 16 weeks from treatment initiation (at delivery)
Reported as:
Median · kg
Infant Weight at Delivery
kgSofosbuvir-Velpatasvir
Infant Weight at Delivery2.90 (2.52 to 3.81)
SecondaryFrequency 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

Time frame:
Up to 16 weeks from treatment initiation (at delivery)
Reported as:
Count of participants · Participants
Frequency of Delivery Modes for Maternal Participants
ParticipantsSofosbuvir-Velpatasvir
Spontaneous vaginal delivery7
Scheduled cesarean section3
Emergent cesarean section1
Assisted vaginal delivery0
SecondaryNumber 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.

Time frame:
Up to 12 months from delivery
Reported as:
Count of participants · Participants
Number of Infant Participants With Congenital Anomalies
ParticipantsSofosbuvir-Velpatasvir
Number of Infant Participants With Congenital Anomalies1
SecondaryWeight of Infant Participant at 1 to 3 Months

Weight of infant participant measured at 1 to 3 months of age

Time frame:
Approximately 3 months from delivery
Reported as:
Median · kg
Weight of Infant Participant at 1 to 3 Months
kgSofosbuvir-Velpatasvir
Weight of Infant Participant at 1 to 3 Months5.6 (4.7 to 6.7)
SecondaryWeight of Infant Participant at 6 Months

Weight of infant participant measured at 6 months of age

Time frame:
Approximately 6 months from delivery
Reported as:
Median · kg
Weight of Infant Participant at 6 Months
kgSofosbuvir-Velpatasvir
Weight of Infant Participant at 6 Months8.4 (6.7 to 9.8)
SecondaryWeight of Infant Participant at 12 Months

Weight of infant participant measured at 12 months of age

Time frame:
Approximately 12 months from delivery
Reported as:
Median · kg
Weight of Infant Participant at 12 Months
kgSofosbuvir-Velpatasvir
Weight of Infant Participant at 12 Months10.6 (8.0 to 11.7)
SecondaryLength of Infant Participant at 1 to 3 Months

Length of infant participant measured at 1 to 3 months of age

Time frame:
Approximately 3 months from delivery
Reported as:
Median · cm
Length of Infant Participant at 1 to 3 Months
cmSofosbuvir-Velpatasvir
Length of Infant Participant at 1 to 3 Months59.0 (53.0 to 65.0)
SecondaryLength of Infant Participant at 6 Months

Length of infant participant measured at 6 months of age

Time frame:
Approximately 6 months from delivery
Reported as:
Median · cm
Length of Infant Participant at 6 Months
cmSofosbuvir-Velpatasvir
Length of Infant Participant at 6 Months67.0 (66.0 to 73.2)
SecondaryLength of Infant Participant at 12 Months

Length of infant participant measured at 12 months of age

Time frame:
Approximately 12 months from delivery
Reported as:
Median · cm
Length of Infant Participant at 12 Months
cmSofosbuvir-Velpatasvir
Length of Infant Participant at 12 Months76.2 (74.5 to 80.0)
SecondaryHead Circumference of Infant Participant at 1 to 3 Months

Head circumference of infant participant measured at 1 to 3 months of age

Time frame:
Approximately 3 months from delivery
Reported as:
Median · cm
Head Circumference of Infant Participant at 1 to 3 Months
cmSofosbuvir-Velpatasvir
Head Circumference of Infant Participant at 1 to 3 Months39.5 (37.0 to 42.0)
SecondaryHead Circumference of Infant Participant at 6 Months

Head circumference of infant participant measured at 6 months of age

Time frame:
Approximately 6 months from delivery
Reported as:
Median · cm
Head Circumference of Infant Participant at 6 Months
cmSofosbuvir-Velpatasvir
Head Circumference of Infant Participant at 6 Months43.4 (42.0 to 45.8)
SecondaryHead Circumference of Infant Participant at 12 Months

Head circumference of infant participant measured at 12 months of age

Time frame:
Approximately 12 months from delivery
Reported as:
Median · cm
Head Circumference of Infant Participant at 12 Months
cmSofosbuvir-Velpatasvir
Head Circumference of Infant Participant at 12 Months46.4 (45.0 to 48.0)
SecondaryQuantity of Hepatitis C Virus in Infant Plasma at Birth

Quantity of Hepatitis C viral RNA measured in infant plasma assessed at birth

Time frame:
Up to 16 weeks from treatment initiation (at delivery)
Reported as:
Median · copies/mL
Quantity of Hepatitis C Virus in Infant Plasma at Birth
copies/mLSofosbuvir-Velpatasvir
Quantity of Hepatitis C Virus in Infant Plasma at BirthNA (NA to NA)
SecondaryQuantity 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

Time frame:
Approximately 3 months from delivery
Reported as:
Median · copies/mL
Quantity of Hepatitis C Virus in Infant Plasma at 1 to 3 Months
copies/mLSofosbuvir-Velpatasvir
Quantity of Hepatitis C Virus in Infant Plasma at 1 to 3 MonthsNA (NA to NA)
SecondaryQuantity 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

Time frame:
Approximately 6 months from delivery
Reported as:
Median · copies/mL
Quantity of Hepatitis C Virus in Infant Plasma at 6 Months
copies/mLSofosbuvir-Velpatasvir
Quantity of Hepatitis C Virus in Infant Plasma at 6 MonthsNA (NA to NA)
SecondaryQuantity 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

Time frame:
Approximately 12 months from delivery
Reported as:
Median · copies/mL
Quantity of Hepatitis C Virus in Infant Plasma at 12 Months
copies/mLSofosbuvir-Velpatasvir
Quantity of Hepatitis C Virus in Infant Plasma at 12 MonthsNA (NA to NA)
SecondaryNumber 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)

Time frame:
Approximately 12 months from delivery
Reported as:
Count of participants · Participants
Number of Infant Participants Referred for Early Neurological Development Intervention
ParticipantsSofosbuvir-Velpatasvir
Number of Infant Participants Referred for Early Neurological Development Intervention1
SecondaryPercentage 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.

Time frame:
Approximately 9 weeks from initiation of maternal treatment

No measurements were reported for this outcome.

SecondaryPercentage 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.

Time frame:
Approximately 9 weeks from initiation of maternal treatment

No measurements were reported for this outcome.

Adverse events

Collected over 6 months from initiation of treatment for maternal participants or 1 year from delivery for infants. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sofosbuvir-Velpatasvir - Maternal Participants0/11 (0%)3/11 (27.3%)11/11 (100%)
Sofosbuvir-Velpatasvir - Infant Participants0/11 (0%)5/11 (45.5%)11/11 (100%)
Most frequent serious events
Most frequent serious events
EventSofosbuvir-Velpatasvir - Maternal ParticipantsSofosbuvir-Velpatasvir - Infant Participants
CholelithiasisGastrointestinal disorders1/110/11
Acute PyelonephritisInfections and infestations1/110/11
Renal calculiRenal and urinary disorders1/110/11
ClubfootCongenital, familial and genetic disorders0/111/11
CryptorchidismReproductive system and breast disorders0/111/11
HyperbilirubinemiaHepatobiliary disorders0/111/11
Respiratory distressRespiratory, thoracic and mediastinal disorders0/111/11
Transient tachypneaRespiratory, thoracic and mediastinal disorders0/111/11
Positive toxicology screenInjury, poisoning and procedural complications0/111/11
Most frequent other events
Showing 10 of 65
Most frequent other events
EventSofosbuvir-Velpatasvir - Maternal ParticipantsSofosbuvir-Velpatasvir - Infant Participants
Upper respiratory tract infectionRespiratory, thoracic and mediastinal disorders0/116/11
HeadacheNervous system disorders4/110/11
AnemiaBlood and lymphatic system disorders4/111/11
COVID-19Respiratory, thoracic and mediastinal disorders3/111/11
Hemorrhage, postpartumPregnancy, puerperium and perinatal conditions3/110/11
VomitingGastrointestinal disorders3/110/11
Otitis mediaEar and labyrinth disorders0/113/11
NauseaGastrointestinal disorders2/110/11
FatigueGeneral disorders2/110/11
Musculoskeletal painMusculoskeletal and connective tissue disorders2/110/11

Baseline characteristics

Maternal baseline characteristics are reported unless otherwise stated

Age, Continuous
Age, Continuous(years)Sofosbuvir-Velpatasvir
Maternal Age, years30 (25 to 39)
Age, Continuous
Age, Continuous(weeks)Sofosbuvir-Velpatasvir
Infant Age, weeks39.00 (35.57 to 39.43)
Sex: Female, Male
Sex: Female, Male(Participants)Sofosbuvir-Velpatasvir
Mothers — Female11
Mothers — Male0
Infants — Female6
Infants — Male5
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Sofosbuvir-Velpatasvir
Mothers — Hispanic or Latino0
Mothers — Not Hispanic or Latino11
Mothers — Unknown or Not Reported0
Infants — Hispanic or Latino1
Infants — Not Hispanic or Latino10
Infants — Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Sofosbuvir-Velpatasvir
Mothers — American Indian or Alaska Native0
Mothers — Asian0
Mothers — Native Hawaiian or Other Pacific Islander0
Mothers — Black or African American1
Mothers — White10
Mothers — More than one race0
Mothers — Unknown or Not Reported0
Infants — American Indian or Alaska Native0
Infants — Asian0
Infants — Native Hawaiian or Other Pacific Islander0
Infants — Black or African American1
Infants — White9
Infants — More than one race1
Infants — Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Sofosbuvir-Velpatasvir
United States22
Hepatitis C Virus Genotype
Hepatitis C Virus Genotype(Participants)Sofosbuvir-Velpatasvir
Genotype 18
Genotype 33
Gestational Age at Treatment Start
Gestational Age at Treatment Start(weeks)Sofosbuvir-Velpatasvir
Median23.43 (23.00 to 25.86)

4 further baseline measures are reported on the registry.

08

Study locations

1 site
  • University of Pittsburgh, Magee Womens Hospital
    Pittsburgh, Pennsylvania 15213, United States
09

References and documents

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 28782502 ↗
  • Gilbert 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 26297552 ↗
  • Chappell 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 31010566 ↗
  • MacBrayne 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. Erratum In: Clin Infect Dis. 2016 Sep 1;63(5):715. doi: 10.1093/cid/ciw459. PubMed 27363437 ↗
  • Kirby 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 25822283 ↗
  • Feld 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 26571066 ↗
  • Foster 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 documents

  • Protocol and statistical analysis plan · Dec 2, 2020
  • Informed consent form · Apr 19, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Data requests can be submitted by email to the Principal Investigator

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 1, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04382404
Lead sponsor
Catherine Anne Chappell
Collaborators
Gilead Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party
Catherine Anne Chappell (Assistant Professor, University of Pittsburgh) — Sponsor-investigator
First posted
May 11, 2020
Start date
Oct 22, 2020
Primary completion
Oct 16, 2023
Completion
Oct 16, 2023
Results posted
Jan 1, 2025
Last update
Jan 1, 2025

Study contacts

Catherine Chappell, MD, MSc
principal investigator · University of Pittsburgh

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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