Treatment of Chronic Hepatitis C During Pregnancy With Sofosbuvir/Velpatasvir

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.

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.

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