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Ledipasvir/Sofosbuvir Fixed-Dose Combination + Ribavirin in Subjects With Chronic HCV With Advanced Liver Disease or Post-Liver Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01938430
First received: September 5, 2013
Last updated: November 12, 2014
Last verified: November 2014
  Purpose

The purpose of this study is to evaluate ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with chronic genotype 1 or 4 hepatitis C virus (HCV) infection. Participants will be randomized to receive 12 or 24 weeks of dosing with the LDV/SOF FDC tablet+ribavirin (RBV).


Condition Intervention Phase
Chronic HCV Infection
Drug: LDV/SOF FDC
Drug: RBV
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir/Ledipasvir Fixed-Dose Combination + Ribavirin Administered in Subjects Infected With Chronic HCV Who Have Advanced Liver Disease or Are Post-Liver Transplant

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of participants with sustained virologic response (SVR12), defined as HCV RNA < lower limit of quantitation (LLOQ) 12 weeks after last dose of study drug [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
  • Proportion of participants who discontinue study drug due to an adverse event [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of participants with sustained virologic response (SVR) at 2, 4, 8 and 24 weeks after discontinuation of therapy (SVR2, SVR4, SVR8 and SVR24) [ Time Frame: Posttreatment Weeks 2, 4, 8, and 24 ] [ Designated as safety issue: No ]
  • Proportion of participants who have HCV RNA < LLOQ by visit while on treatment [ Time Frame: Weeks 1, 2, 4, 6, 8, and 12 ] [ Designated as safety issue: No ]
  • HCV RNA levels and change from Day 1 through Week 8 [ Time Frame: Baseline to Weeks 1, 2, 4, 6, and 8 ] [ Designated as safety issue: No ]
  • Proportion of participants with virologic failure [ Time Frame: Baseline to Posttreatment Week 24 ] [ Designated as safety issue: No ]
  • Change in model for end-stage liver disease (MELD) and Child-Pugh-Turcotte (CPT) scores [ Time Frame: Baseline through posttreatment Week 24 ] [ Designated as safety issue: No ]
  • Proportion of participants with post-transplant virologic response [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    For those participants who have a liver transplant while on study, the proportion of participants with post-transplant virologic response (PTVR, defined as HCV RNA < LLOQ at 12 weeks post-transplant) will be summarized for participants in the Full Analysis Set (FAS) who have HCV RNA < LLOQ at their last observed HCV RNA prior to transplant.


Estimated Enrollment: 400
Study Start Date: September 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Cohort A, advanced liver disease Group 1. Participants with cirrhosis and moderate hepatic impairment (CPT Class B) will be randomized to receive either 12 or 24 weeks of LDV/SOF plus RBV.
Drug: LDV/SOF FDC
LDV 400 mg/SOF 90 mg FDC tablet administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
Drug: RBV
RBV administered as 200 mg tablets (up to 1000-1200 mg) in a divided daily dose
Experimental: Group 2
Cohort A, advanced liver disease Group 2. Participants with cirrhosis and severe hepatic impairment (CPT Class C) will be randomized to receive either 12 or 24 weeks of LDV/SOF plus RBV.
Drug: LDV/SOF FDC
LDV 400 mg/SOF 90 mg FDC tablet administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
Drug: RBV
RBV administered as 200 mg tablets (up to 1000-1200 mg) in a divided daily dose
Experimental: Group 3
Cohort B, post-transplant Group 3. Participants without cirrhosis (fibrosis stage F0-F3) and with no evidence of hepatic decompensation will be randomized to receive either 12 or 24 weeks of LDV/SOF plus RBV.
Drug: LDV/SOF FDC
LDV 400 mg/SOF 90 mg FDC tablet administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
Drug: RBV
RBV administered as 200 mg tablets (up to 1000-1200 mg) in a divided daily dose
Experimental: Group 4
Cohort B, post-transplant Group 4. Participants with cirrhosis and mild hepatic impairment (CPT Class A) will be randomized to receive either 12 or 24 weeks of LDV/SOF plus RBV.
Drug: LDV/SOF FDC
LDV 400 mg/SOF 90 mg FDC tablet administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
Drug: RBV
RBV administered as 200 mg tablets (up to 1000-1200 mg) in a divided daily dose
Experimental: Group 5
Cohort B, post-transplant Group 5. Participants with cirrhosis and moderate hepatic impairment (CPT Class B) will be randomized to receive either 12 or 24 weeks of LDV/SOF plus RBV.
Drug: LDV/SOF FDC
LDV 400 mg/SOF 90 mg FDC tablet administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
Drug: RBV
RBV administered as 200 mg tablets (up to 1000-1200 mg) in a divided daily dose
Experimental: Group 6
Cohort B, post-transplant Group 6. Participants with cirrhosis and severe hepatic impairment (CPT Class C) will be randomized to receive either 12 or 24 weeks of LDV/SOF plus RBV.
Drug: LDV/SOF FDC
LDV 400 mg/SOF 90 mg FDC tablet administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
Drug: RBV
RBV administered as 200 mg tablets (up to 1000-1200 mg) in a divided daily dose
Experimental: Group 7
Cohort B, post-transplant Group 7. Participants with aggressive recurrent disease after transplant with evidence of cholestasis (fibrosing cholestatic hepatitis [FCH]) will be randomized to receive either 12 or 24 weeks of LDV/SOF plus RBV.
Drug: LDV/SOF FDC
LDV 400 mg/SOF 90 mg FDC tablet administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • GS-5885
Drug: RBV
RBV administered as 200 mg tablets (up to 1000-1200 mg) in a divided daily dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Able to provide written informed consent
  • Chronic genotype 1 or 4 HCV infection
  • Normal ECG
  • Negative serum pregnancy test for female subjects
  • Male subjects and female subjects of childbearing potential must agree to use contraception
  • Able to comply with the dosing instructions for study drug and able to complete the study schedule of assessments, including all required post treatment visits

Exclusion Criteria

  • Serious or active medical or psychiatric illness
  • HIV or hepatitis B viral (HBV) infection
  • Stomach disorder that could interfere with the absorption of the study drug
  • Treated with an anti-HCV medication in the last 30 days
  • Any prior exposure to an HCV nonstructural protein (NS)5a-specific inhibitor
  • Use of human granulocyte-macrophage colony-stimulating factor (GM-CSF), epoetin alfa or other therapeutic hematopoietic agents within 2 weeks of screening
  • History of clinically significant medical condition associated with other chronic liver disease
  • Active spontaneous bacterial peritonitis at screening
  • Females who are breastfeeding
  • Infection requiring systemic antibiotics
  • Participated in a clinical study with an investigational drug or biologic within the last 30 days
  • Active or history (last 6 months) of drug or alcohol abuse
  • History of organ transplant other than liver or kidney
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01938430

  Show 30 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jill Denning Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01938430     History of Changes
Other Study ID Numbers: GS-US-337-0123
Study First Received: September 5, 2013
Last Updated: November 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on November 27, 2014