Study of Hepatitis C Treatment During Pregnancy
Condition: Hepatitis C; Pregnancy
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      Sofosbuvir and ledipasvir (LDV/SOF) are new directly acting antiviral drugs for the treatment
      of hepatitis C (HCV) that are highly effective, orally administered, well tolerated and
      preclinical evaluations in animal models indicate safe administration during pregnancy. This
      project will evaluate the safety and pharmacokinetics of antenatal LDV/SOF treatment for 12
      weeks during the second and third trimester. If proven to be effective, antenatal treatment
      of HCV with LDV/SOF will prevent maternal HCV-related liver disease, perinatal transmission
      of HCV, and community transmission of HCV.
    

Detailed description: 
      There are 3.2 million persons in the United States chronically infected with hepatitis C
      virus (HCV) with a 1-2.4% prevalence during pregnancy. The recent October 2014 approval of
      the fixed dose combination, containing the NS5B polymerase inhibitor sofosbuvir (SOF) 90 mg
      and the NS5A inhibitor ledipasvir (LDV) 400mg, marked a new era of IFN and ribavirin free,
      directly acting antiviral treatment for HCV. A 12 week treatment course of LDV/SOF resulted
      in a 99% cure rate when given as a once-a-day oral pill. Based on the animal model data
      submitted to the FDA, this drug combination was given a pregnancy category B designation,
      even though there is currently no experience with LDV/SOF in pregnant women.

      Pregnancy is a time when women are uniquely motivated to engage in activities which are
      geared toward improvement of their own health and ensuring the health of their unborn child.
      As such, pregnant women have frequent prenatal care visits; and health care interventions,
      such as antiviral therapy and monitoring, can be easily integrated into the existing
      healthcare infrastructure of prenatal care. The benefits of HCV treatment are numerous,
      including prevention of severe liver disease, hepatocellular carcinoma, and liver
      transplantation, as well as improvements physical, emotional and social health. The most
      recent guidelines by the Infectious Disease Society of America recommend that all
      HCV-infected persons receive treatment. The antenatal period represents an ideal window of
      opportunity for treatment of HCV in pregnancy due to increased antenatal health care
      utilization and prevention of perinatal transmission of HCV to the infant.

      Safe administration of drugs in pregnancy may require dose adjustment due to the
      pregnancy-induced physiologic alternations. Therefore, careful pharmacokinetic (PK)
      evaluation is a critical first step to ensure safe administration of drugs to both the mother
      and the developing fetus. This is a single-arm, single-center, open label Phase 1 evaluation
      of the PK and safety of treating HCV with a 12 week course of LDV/SOF in 15 HCV-infected
      pregnant women. Therapy will be initiated at approximately 24 weeks of gestation. In this
      study we will determine: 1) if the PK of the LDV and SOF are similar in pregnancy as compared
      to those in nonpregnant women, 2) if the viral response to LDV/SOF treatment in pregnancy is
      similar to that observed in nonpregnant women, and 3) if there are any initial maternal or
      neonatal safety concerns detected with antenatal LDV/SOF administration compared with
      HCV-infected historical controls delivered at our institution. From the findings of this
      study, future studies will seek to optimize the dose, gestational age timing and treatment
      duration of LDV/SOF during pregnancy. Antenatal HCV treatment will improve maternal health,
      prevent further HCV transmission in the community and perinatal HCV transmission to the
      child, and thus enhance the long-term health of two generations.
    

Intervention name(s): ledipasvir/sofosbuvir
Intervention type(s): Drug
Intervention description(s): Hepatitis C treatment with ledipasvir and sofosbuvir will be initiated during pregnancy at approximately 24 weeks of gestation.
Other intervention name(s): Harvoni
Intervention MeSH terms: Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: treatment; pharmacokinetics