Study of Hepatitis C Treatment During Pregnancy

NCT02683005 | Completed Phase 1 DMC

• 1 other identifier: PRO16010091
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatitis C; Pregnancy

Keywords

treatment; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Area Under Curve (AUC) Time Frame: predose, 0.5 hr, 1 hr, 2, 3, 4, 5, 8, 12 hrs

  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

  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

Secondary Outcomes (8)

• Sustained viral response at 12 weeks post treatment (SVR 12)

  -HCV RNA viral load will be assessed at 12 weeks after completion of LDV/SOF treatment

• Number of Maternal Adverse Events

  -From enrollment to 12 weeks after treatment completion

• Number of Participants With Abnormal Laboratory Values

  -From enrollment to 12 weeks after treatment completion

• Major Malformations of the Neonate

  From birth until 1 year of life

• Length

  From birth until 1 year of life

Study Arms (1)

Ledipasvir/Sofosbuvir

EXPERIMENTAL

Hepatitis C treatment will be initiated with ledipasvir (400 mg) and sofosbuvir (90mg) fixed dose combination, one pill, once daily for 12 weeks.

Drug: ledipasvir/sofosbuvir

Interventions

ledipasvir/sofosbuvir DRUG

Hepatitis C treatment with ledipasvir and sofosbuvir will be initiated during pregnancy at approximately 24 weeks of gestation.

Also known as: Harvoni

Ledipasvir/Sofosbuvir

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 through 39 years (inclusive) at Screening
• Able and willing to provide written informed consent to be screened for and take part in the study procedures
• Able and willing to provide adequate locator information
• Chronic HCV, genotype 1, 4, 5, 6 infection, defined as HCV antibody detected at least 6 months prior to Screening and detectable HCV RNA viral load at Screening
• Desired pregnancy at 23 + 0 to 24 + 6 weeks' gestation at Enrollment with gestational dating confirmed by ultrasound
• Singleton gestation with no known fetal abnormalities
• Documented negative Hepatitis B testing for current infection (negative HBsAg 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

You may not qualify if:

• Participant report of any of the following at Screening or Enrollment:
• Previous treatment for Hepatitis C virus with an NS5A inhibitor or sofosbuvir
• Use of any medications contraindicated with concurrent use of ledipasvir or sofobuvir according to the most current HARVONI package insert
• Plans to relocate away from the study site area in the next 1 year and 4 months
• Current sexual partner is known to be infected with HIV or Hepatitis B virus
• History of cirrhosis documented 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:
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 10 times the upper limited of normal
• Hemoglobin less than 9 g/dL
• Platelet count less than 90,000 per mm3
• International normalized ratio (INR) \> 1.5

Sponsors & Collaborators

• Catherine Chappell: lead
• Gilead Sciences: collaborator
• University of Nebraska: collaborator

Study Sites (1)

Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Chappell CA, Scarsi KK, Kirby BJ, Suri V, Gaggar A, Bogen DL, Macio IS, Meyn LA, Bunge KE, Krans EE, Hillier SL. Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study. Lancet Microbe. 2020 Sep;1(5):e200-e208. doi: 10.1016/S2666-5247(20)30062-8. Epub 2020 Jul 27.

  PMID: 32939459 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Catherine A Chappell, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: February 17, 2016
• Study Start: September 1, 2016
• Primary Completion: February 3, 2020
• Study Completion: February 3, 2020
• Last Updated: March 4, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)