Study of Hepatitis C Treatment During Pregnancy (HIP)
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|ClinicalTrials.gov Identifier: NCT02683005|
Recruitment Status : Active, not recruiting
First Posted : February 17, 2016
Last Update Posted : December 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hepatitis C Pregnancy||Drug: ledipasvir/sofosbuvir||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Pharmacokinetic and Safety Trial of Ledipasvir/Sofosbuvir Fixed Dose Combination in Pregnant Women With Chronic Hepatitis C Virus Infection|
|Actual Study Start Date :||September 2016|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||February 2020|
Hepatitis C treatment will be initiated with ledipasvir (400 mg) and sofosbuvir (90mg) fixed dose combination, one pill, once daily for 12 weeks.
Hepatitis C treatment with ledipasvir and sofosbuvir will be initiated during pregnancy at approximately 24 weeks of gestation.
Other Name: Harvoni
- Area Under Curve (AUC) Time Frame: predose, 0.5 hr, 1 hr, 2, 3, 4, 5, 8, 12 hrs [ Time Frame: 3 gestational age time points during the 12 weeks of treatment: 1) Between 25 + 0 and 26 + 5; 2) Between 29 + 0 and 30 + 6; 3) 33 + 0 and 34 + 6 weeks' gestation ]Systemic exposure both LDV and SOF (SOF and inactive metabolite GS-331007) will be assessed at 3 gestational age time points: 1) Late second trimester between 25 + 0 and 26 + 5 weeks' gestation (after at least 10 days of therapy); 2) Early third trimester between 29 + 0 and 30 + 6 weeks' gestation; 3) Late third trimester between 33 + 0 and 34 + 6 weeks' gestation
- Sustained viral response at 12 weeks post treatment (SVR 12) [ Time Frame: -HCV RNA viral load will be assessed at 12 weeks after completion of LDV/SOF treatment ]An undetectable HCV viral load is considered an SVR 12.
- Number of Maternal Adverse Events [ Time Frame: -From enrollment to 12 weeks after treatment completion ]Adverse events, including pregnancy and delivery outcomes will be collected prospectively . -
- Number of Participants With Abnormal Laboratory Values [ Time Frame: -From enrollment to 12 weeks after treatment completion ]Safety laboratories will be sent 4-6 weeks after the initiation of treatment and will include CBC, chemistries, liver function tests, creatinine kinase, lipase, and coagulation studies.
- Major Malformations of the Neonate [ Time Frame: From birth until 1 year of life ]Major malformations, defined as structural abnormalities with surgical, medical, or cosmetic importance
- Length [ Time Frame: From birth until 1 year of life ]Length in centimeters will be collected at birth, 1 month, 6 months, and 12 months.
- Weight [ Time Frame: From birth until 1 year of life ]Weight in kilograms will be collected at birth, 1 month, 6 months, and 12 months.
- Head circumference [ Time Frame: From birth until 1 year of life ]Head circumference (centimeters) will be collected at birth, 1 month, 6 months and 12 months.
- Perninatal Hepatitis C Transmission [ Time Frame: From birth until 1 year of life ]Perinatal HCV transmission assessed by presence of hepatitis C virus RNA from infant blood sampling at one month, six months and 12 months.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02683005
|United States, Pennsylvania|
|Magee Womens Hospital|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Catherine A Chappell, MD||University of Pittsburgh|