Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01938430
First received: September 5, 2013
Last updated: March 16, 2016
Last verified: March 2016
  Purpose

This study will evaluate ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) in participants with advanced liver disease or posttransplant and chronic genotype 1 or 4 hepatitis C virus (HCV) infection.

  • Cohort A: decompensated cirrhosis (advanced liver disease), no prior liver transplant;
  • Cohort B: post-liver transplant, with or without cirrhosis;
  • Group assignment within cohorts is based on severity of liver impairment at screening (Child-Pugh-Turcotte (CPT) score for participants with cirrhosis; fibrosis; or presence of disease for fibrosing cholestatic hepatitis (FCH) groups)
  • Randomization is 1:1 within groups to 12 or 24 weeks of LDV/SOF+RBV treatment.

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

Study Type: Interventional
Study Design: Allocation: 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:
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

  • Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2) [ Time Frame: Posttreatment Week 2 ] [ Designated as safety issue: No ]
    SVR2 was defined as HCV RNA < LLOQ at 2 weeks after stopping study treatment.

  • Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ] [ Designated as safety issue: No ]
    SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.

  • Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8) [ Time Frame: Posttreatment Week 8 ] [ Designated as safety issue: No ]
    SVR8 was defined as HCV RNA < LLOQ at 8 weeks after stopping study treatment.

  • Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ] [ Designated as safety issue: No ]
    SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.

  • Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ] [ Designated as safety issue: No ]

    Virologic failure was defined as:

    • On-treatment virologic failure:

      • Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ on 2 consecutive measurements while on treatment), or
      • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment)
    • Virologic relapse:

      • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

  • Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12 [ Time Frame: Posttransplant Week 12 ] [ Designated as safety issue: No ]
    pTVR was defined as HCV RNA < LLOQ at Week 12 after transplant.

  • Percentage of Participants With HCV RNA < LLOQ at Week 1 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 16 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 20 [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HCV RNA < LLOQ at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • HCV RNA and Change From Baseline at Week 1 [ Time Frame: Baseline; Week 1 ] [ Designated as safety issue: No ]
  • HCV RNA and Change From Baseline at Week 2 [ Time Frame: Baseline; Week 2 ] [ Designated as safety issue: No ]
  • HCV RNA and Change From Baseline at Week 4 [ Time Frame: Baseline; Week 4 ] [ Designated as safety issue: No ]
  • HCV RNA and Change From Baseline at Week 6 [ Time Frame: Baseline; Week 6 ] [ Designated as safety issue: No ]
  • HCV RNA and Change From Baseline at Week 8 [ Time Frame: Baseline; Week 8 ] [ Designated as safety issue: No ]
  • HCV RNA and Change From Baseline at Week 12 [ Time Frame: Baseline; Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in MELD Score [ Time Frame: Baseline to Posttreatment Week 4 ] [ Designated as safety issue: No ]
    Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease.

  • Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in CPT Score [ Time Frame: Baseline to Posttreatment Week 4 ] [ Designated as safety issue: No ]
    CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15 (maximum score for entry into the study was 12); higher scores/increased scores indicate greater severity of disease. Groups are arranged by cohort, then by duration of treatment, then by CPT class at baseline.


Enrollment: 339
Study Start Date: September 2013
Study Completion Date: March 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A, Group 1 (12 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class B (CPT score 7-9)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort A, Group 1 (24 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class B (CPT score 7-9)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort A, Group 2 (12 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class C (CPT score 10-12)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort A, Group 2 (24 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class C (CPT score 10-12)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 3 (12 wk): F0-F3 Fibrosis
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with Fibrosis Stage F0-F3.
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 3 (24 wk): F0-F3 Fibrosis
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with Fibrosis Stage F0-F3
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 4 (12 wk): CPT Class A (5-6)
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with CPT Class A (CPT score 5-6)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 4 (24 wk): CPT Class A (5-6)
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with CPT Class A (CPT score 5-6)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 5 (12 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class B (CPT score 7-9)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 5 (24 wk): CPT Class B (7-9)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class B (CPT score 7-9)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 6 (12 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 12 weeks in participants with CPT Class C (CPT score 10-12)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 6 (24 wk): CPT Class C (10-12)
LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability [weight-based maximum: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg]) for 24 weeks in participants with CPT Class C (CPT score 10-12)
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 7 (12 wk): FCH
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with FCH
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose
Experimental: Cohort B, Group 7 (24 wk): FCH
LDV/SOF (90/400 mg) plus RBV (weight-based: < 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with FCH
Drug: LDV/SOF
LDV/SOF FDC tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Drug: RBV
RBV tablets administered orally in a divided daily dose

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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: Shampa De-Oertel, PhD Gilead Sciences
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Results First Received: March 16, 2016
Last Updated: March 16, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Ribavirin
Sofosbuvir
Ledipasvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 27, 2016