Hepatitis C, Chronic
Conditions
Keywords
pregnancy
Brief summary
A single-arm, single-center, open label Phase 1 study of a 12-week course of Sofosbuvir (SOF)/Velpatasvir (VEL) in 10 HCV-infected pregnant women 1 that will evaluate the plasma pharmacokinetic parameters of SOF/VEL administered during pregnancy and compare them to those of a historical cohort of nonpregnant women.
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.
Interventions
DRUGSofosbuvir-Velpatasvir Drug Combination
One oral pill containing 400mg sofosbuvir and 100mg velpatasvir taken once daily for 12 weeks
Sponsors
Gilead Sciences
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Catherine Anne Chappell
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, single arm
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration of Velpatasvir in Maternal Plasma | 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 | 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 | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantity of Hepatitis C Virus in Maternal Plasma After Completion of Velpatasvir and Sofosbuvir Treatment | 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 |
| Number of Maternal and Infant Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir | 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 |
| Maternal Gestational Age at Delivery | Up to 16 weeks from treatment initiation (at delivery) | Maternal gestational age at delivery determined by medical record review |
| Infant Weight at Delivery | Up to 16 weeks from treatment initiation (at delivery) | Infant birth weight determined by medical record review |
| Frequency of Delivery Modes for Maternal Participants | 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 |
| Number of Infant Participants With Congenital Anomalies | 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. |
| Weight of Infant Participant at 1 to 3 Months | Approximately 3 months from delivery | Weight of infant participant measured at 1 to 3 months of age |
| Weight of Infant Participant at 6 Months | Approximately 6 months from delivery | Weight of infant participant measured at 6 months of age |
| Weight of Infant Participant at 12 Months | Approximately 12 months from delivery | Weight of infant participant measured at 12 months of age |
| Length of Infant Participant at 1 to 3 Months | Approximately 3 months from delivery | Length of infant participant measured at 1 to 3 months of age |
| Length of Infant Participant at 6 Months | Approximately 6 months from delivery | Length of infant participant measured at 6 months of age |
| Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 3 Weeks | 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 |
| Head Circumference of Infant Participant at 1 to 3 Months | Approximately 3 months from delivery | Head circumference of infant participant measured at 1 to 3 months of age |
| Head Circumference of Infant Participant at 6 Months | Approximately 6 months from delivery | Head circumference of infant participant measured at 6 months of age |
| Head Circumference of Infant Participant at 12 Months | Approximately 12 months from delivery | Head circumference of infant participant measured at 12 months of age |
| Quantity of Hepatitis C Virus in Infant Plasma at Birth | Up to 16 weeks from treatment initiation (at delivery) | Quantity of Hepatitis C viral RNA measured in infant plasma assessed at birth |
| Quantity of Hepatitis C Virus in Infant Plasma at 1 to 3 Months | Approximately 3 months from delivery | Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 1 to 3 months of age |
| Quantity of Hepatitis C Virus in Infant Plasma at 6 Months | Approximately 6 months from delivery | Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 6 months of age |
| Quantity of Hepatitis C Virus in Infant Plasma at 12 Months | Approximately 12 months from delivery | Quantity of Hepatitis C viral RNA measured in infant plasma assessed at 12 months of age |
| Number of Infant Participants Referred for Early Neurological Development Intervention | 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) |
| Percentage of Unbound Sofosbuvir Measured in Maternal Plasma | 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. |
| Percentage of Unbound Velpatasvir Measured in Maternal Plasma | 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. |
| Length of Infant Participant at 12 Months | Approximately 12 months from delivery | Length of infant participant measured at 12 months of age |
| Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 6 Weeks | 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 |
| Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 9 Weeks | 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 |
| Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 3 Weeks | 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 |
| Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 6 Weeks | 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 |
| Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 9 Weeks | 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 |
Countries
United States
Participant flow
Pre-assignment details
11 mother-infant dyads were enrolled
Participants by arm
| Arm | Count |
|---|---|
| Sofosbuvir-Velpatasvir One oral pill containing 400mg sofosbuvir and 100mg velpatasvir taken once daily for 12 weeks | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Sofosbuvir-Velpatasvir |
|---|---|
| Age, Continuous Infant Age, weeks | 39.00 weeks |
| Age, Continuous Maternal Age, years | 30 years |
| Body Mass Index | 27.0 kg/m2 |
| Ethnicity (NIH/OMB) Infants Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Infants Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Infants Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Mothers Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Mothers Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Mothers Unknown or Not Reported | 0 Participants |
| Gestational Age at Treatment Start | 23.43 weeks |
| Hematocrit | 36 percent |
| Hepatitis C Virus Genotype Genotype 1 | 8 Participants |
| Hepatitis C Virus Genotype Genotype 3 | 3 Participants |
| Race (NIH/OMB) Infants American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Infants Asian | 0 Participants |
| Race (NIH/OMB) Infants Black or African American | 1 Participants |
| Race (NIH/OMB) Infants More than one race | 1 Participants |
| Race (NIH/OMB) Infants Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Infants Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Infants White | 9 Participants |
| Race (NIH/OMB) Mothers American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Mothers Asian | 0 Participants |
| Race (NIH/OMB) Mothers Black or African American | 1 Participants |
| Race (NIH/OMB) Mothers More than one race | 0 Participants |
| Race (NIH/OMB) Mothers Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Mothers Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Mothers White | 10 Participants |
| Region of Enrollment United States | 22 participants |
| Serum Creatinine | 0.5 mg/dL |
| Sex: Female, Male Infants Female | 6 Participants |
| Sex: Female, Male Infants Male | 5 Participants |
| Sex: Female, Male Mothers Female | 11 Participants |
| Sex: Female, Male Mothers Male | 0 Participants |
| Weight Infants | 2.9 kg |
| Weight Mothers | 73.5 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 11 / 11 | 11 / 11 |
| serious Total, serious adverse events | 3 / 11 | 5 / 11 |
Outcome results
Primary
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
Population: 10 participants had results from 2 or more visits; 1 participant discontinued study drug after one dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sofosbuvir-Velpatasvir | Area Under the Maternal Plasma Concentration Versus Time Curve of GS-331007 | 9558.94 hr*ng/mL | Geometric Coefficient of Variation 18.75 |
Comparison: Area under the plasma concentration versus time curve tau of Sofosbuvir was compared between the 10 pregnant women in this study to 25 non-pregnant historical control women. The geometric mean (percent coefficient of variation) for the non-pregnant cohort was 15361.31 (22.35).90% CI: [0.55, 0.71]
Primary
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
Population: 10 participants had results from 2 or more visits; 1 participant discontinued study drug after one dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sofosbuvir-Velpatasvir | Area Under the Maternal Plasma Concentration Versus Time Curve of Sofosbuvir | 2039.62 hr*ng/mL | Geometric Coefficient of Variation 29.75 |
Comparison: Area under the plasma concentration versus time curve tau of Sofosbuvir was compared between the 10 pregnant women in this study to 25 non-pregnant historical control women. The geometric mean (percent coefficient of variation) for the non-pregnant cohort was 1483.83 (66.43).90% CI: [1.06, 1.78]
Primary
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
Population: 10 participants had results from 2 or more visits; 1 participant discontinued study drug after one dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sofosbuvir-Velpatasvir | Area Under the Maternal Plasma Concentration Versus Time Curve of Velpatasvir | 3244.45 hr*ng/mL | Geometric Coefficient of Variation 39.89 |
Comparison: Area under the plasma concentration versus time curve tau of Velpatasvir was compared between the 10 pregnant women in this study to 25 non-pregnant historical control women. The geometric mean (percent coefficient of variation) for the non-pregnant cohort was 3570.65 (72.04).90% CI: [0.67, 1.23]
Primary
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
Population: 10 maternal participants had results from 2 or more visits; 1 maternal participant discontinued study drug after one dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sofosbuvir-Velpatasvir | Maximum Concentration of GS-331007 in Maternal Plasma | 752.66 ng/mL | Geometric Coefficient of Variation 21.85 |
Comparison: Maximum concentration of GS-331007 in plasma was compared between the 10 pregnant women in this study to 25 non-pregnant historical control women. The geometric mean concentration (percent coefficient of variation) for the non-pregnant cohort was 1312.17 (32.55).90% CI: [0.49, 0.67]
Primary
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
Population: 10 maternal participants had results from 2 or more visits; 1 maternal participant discontinued study drug after one dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sofosbuvir-Velpatasvir | Maximum Concentration of Sofosbuvir in Maternal Plasma | 1455.09 ng/mL | Geometric Coefficient of Variation 43.92 |
Comparison: Maximum concentration of Sofosbuvir in plasma was compared between the 10 pregnant women in this study to 25 non-pregnant historical control women. The geometric mean concentration (percent coefficient of variation) for the non-pregnant cohort was 1226.16 (59.46).90% CI: [0.88, 1.6]
Primary
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
Population: 10 maternal participants had results from 2 or more visits; 1 maternal participant discontinued study drug after one dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sofosbuvir-Velpatasvir | Maximum Concentration of Velpatasvir in Maternal Plasma | 381.93 ng/mL | Geometric Coefficient of Variation 38.35 |
Comparison: Maximum concentration of Velpatasvir in plasma was compared between the 10 pregnant women in this study to 25 non-pregnant historical control women. The geometric mean concentration (percent coefficient of variation) for the non-pregnant cohort was 449.39 (77.12).90% CI: [0.63, 1.15]
Secondary
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)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sofosbuvir-Velpatasvir | Frequency of Delivery Modes for Maternal Participants | Spontaneous vaginal delivery | 7 Participants |
| Sofosbuvir-Velpatasvir | Frequency of Delivery Modes for Maternal Participants | Scheduled cesarean section | 3 Participants |
| Sofosbuvir-Velpatasvir | Frequency of Delivery Modes for Maternal Participants | Emergent cesarean section | 1 Participants |
| Sofosbuvir-Velpatasvir | Frequency of Delivery Modes for Maternal Participants | Assisted vaginal delivery | 0 Participants |
Secondary
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
Population: Two infant participants were lost to follow-up; head circumference not assessed for 2 infant participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Head Circumference of Infant Participant at 12 Months | 46.4 cm |
Secondary
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
Population: Two infant participants were lost to follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Head Circumference of Infant Participant at 1 to 3 Months | 39.5 cm |
Secondary
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
Population: Two infant participants were lost to follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Head Circumference of Infant Participant at 6 Months | 43.4 cm |
Secondary
Infant Weight at Delivery
Infant birth weight determined by medical record review
Time frame: Up to 16 weeks from treatment initiation (at delivery)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Infant Weight at Delivery | 2.90 kg |
Secondary
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
Population: One participant discontinued study medication after the second daily dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 3 Weeks | 340 fmol/punch |
Comparison: The geometric mean (95 percent confidence interval) concentration of GS-461203 in dried blood spots was compared between the pregnant cohort and 58 nonpregnant persons. The geometric mean (95 percent confidence interval) concentration of GS-461203 was 647 (571, 723) fmol/punch in the nonpregnant cohort.95% CI: [0.5, 0.56]
Secondary
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
Population: One participant discontinued study medication after the second daily dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 6 Weeks | 340 fmol/punch |
Comparison: The geometric mean (95 percent confidence interval) concentration of GS-461203 in dried blood spots was compared between the pregnant cohort and 58 nonpregnant persons. The geometric mean (95 percent confidence interval) concentration of GS-461203 was 647 (571, 723) fmol/punch in the nonpregnant cohort.95% CI: [0.49, 0.58]
Secondary
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
Population: One participant discontinued study medication after the second daily dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Intracellular Concentration of GS-461203 From Dried Maternal Blood Spots at 9 Weeks | 356 fmol/punch |
Comparison: The geometric mean (95 percent confidence interval) concentration of GS-461203 in dried blood spots was compared between the pregnant cohort and 58 nonpregnant persons. The geometric mean (95 percent confidence interval) concentration of GS-461203 was 647 (571, 723) fmol/punch in the nonpregnant cohort.95% CI: [0.48, 0.64]
Secondary
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
Population: One participant discontinued study medication after the second daily dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 3 Weeks | 2111 fmol/10^6 cells |
Comparison: The geometric mean (95 percent confidence interval) concentration of GS-461203 in peripheral blood mononuclear cells was compared between the pregnant cohort and 58 nonpregnant persons. The geometric mean (95 percent confidence interval) concentration of GS-461203 was 1474 (488, 4453) fmol /10\^6 cells in the nonpregnant cohort.95% CI: [0.91, 2.25]
Secondary
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
Population: One participant discontinued study medication after the second daily dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 6 Weeks | 2808 fmol/10^6 cells |
Comparison: The geometric mean (95 percent confidence interval) concentration of GS-461203 in peripheral blood mononuclear cells was compared between the pregnant cohort and 58 nonpregnant persons. The geometric mean (95 percent confidence interval) concentration of GS-461203 was 1474 (488, 4453) fmol /10\^6 cells in the nonpregnant cohort.95% CI: [1.14, 3.19]
Secondary
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
Population: One participant discontinued study medication after the second daily dose
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Intracellular Concentration of GS-461203 From Maternal Peripheral Blood Mononuclear Cells at 9 Weeks | 2212 fmol/10^6 cells |
Comparison: The geometric mean (95 percent confidence interval) concentration of GS-461203 in peripheral blood mononuclear cells was compared between the pregnant cohort and 58 nonpregnant persons. The geometric mean (95 percent confidence interval) concentration of GS-461203 was 1474 (488, 4453) fmol /10\^6 cells in the nonpregnant cohort.95% CI: [0.87, 2.6]
Secondary
Length of Infant Participant at 12 Months
Length of infant participant measured at 12 months of age
Time frame: Approximately 12 months from delivery
Population: Two infant participants were lost to follow-up; length not assessed for 1 infant participant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Length of Infant Participant at 12 Months | 76.2 cm |
Secondary
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
Population: Two infant participants were lost to follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Length of Infant Participant at 1 to 3 Months | 59.0 cm |
Secondary
Length of Infant Participant at 6 Months
Length of infant participant measured at 6 months of age
Time frame: Approximately 6 months from delivery
Population: Two infant participants were lost to follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Length of Infant Participant at 6 Months | 67.0 cm |
Secondary
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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Maternal Gestational Age at Delivery | 39.00 weeks |
Secondary
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
Population: Two infant participants were lost to follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Number of Infant Participants Referred for Early Neurological Development Intervention | 1 Participants |
Secondary
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
Population: Infant participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Number of Infant Participants With Congenital Anomalies | 1 Participants |
Secondary
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
Population: There were 11 maternal-infant dyads
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Number of Maternal and Infant Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir | 9 Participants |
| Sofosbuvir-Velpatasvir - Infant Participants | Number of Maternal and Infant Participants That Experience Adverse Events Related to Sofosbuvir/Velpatasvir | 0 Participants |
Secondary
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
Population: Assay was not done.
Secondary
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
Population: Assay was not done
Secondary
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
Population: Unable to obtain blood draw on 1 infant, 3 infants were lost to follow-up, 1 infant born maternal participant that did not complete study medication, Hepatitis C viral RNA assessment not required from 4 infants per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Quantity of Hepatitis C Virus in Infant Plasma at 12 Months | NA copies/mL |
Secondary
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
Population: Unable to obtain blood draw on 1 infant, 2 infants were lost to follow-up, 1 infant born maternal participant that did not complete study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Quantity of Hepatitis C Virus in Infant Plasma at 1 to 3 Months | NA copies/mL |
Secondary
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
Population: Unable to obtain blood draw on 2 infants, 3 infants were lost to follow-up, 1 infant born maternal participant that did not complete study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Quantity of Hepatitis C Virus in Infant Plasma at 6 Months | NA copies/mL |
Secondary
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)
Population: One infant delivered at a non-study site hospital where Hepatitis C viral RNA in plasma was not assessed; 1 infant born maternal participant that did not complete study medication
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Quantity of Hepatitis C Virus in Infant Plasma at Birth | NA copies/mL |
Secondary
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
Population: One participant discontinued study medication after the second daily dose, one participant was lost to follow-up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Quantity of Hepatitis C Virus in Maternal Plasma After Completion of Velpatasvir and Sofosbuvir Treatment | NA copies/mL |
Secondary
Weight of Infant Participant at 12 Months
Weight of infant participant measured at 12 months of age
Time frame: Approximately 12 months from delivery
Population: Two infant participants were lost to follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Weight of Infant Participant at 12 Months | 10.6 kg |
Secondary
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
Population: Two infant participants were lost to follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Weight of Infant Participant at 1 to 3 Months | 5.6 kg |
Secondary
Weight of Infant Participant at 6 Months
Weight of infant participant measured at 6 months of age
Time frame: Approximately 6 months from delivery
Population: Two infant participants were lost to follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sofosbuvir-Velpatasvir | Weight of Infant Participant at 6 Months | 8.4 kg |