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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02010255
Recruitment Status : Completed
First Posted : December 12, 2013
Results First Posted : June 20, 2016
Last Update Posted : November 19, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Chronic HCV Infection Drug: LDV/SOF Drug: RBV Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 334 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : January 2014
Actual Primary Completion Date : May 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

  2. Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :
  1. Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2) [ Time Frame: Posttreatment Week 2 ]
    SVR2 was defined as HCV RNA < LLOQ at 2 weeks after stopping study treatment.

  2. Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
    SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.

  3. Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8) [ Time Frame: Posttreatment Week 8 ]
    SVR8 was defined as HCV RNA < LLOQ at 8 weeks after stopping study treatment.

  4. Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
    SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.

  5. Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ]

    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.

  6. Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12 [ Time Frame: Posttreatment Week 12 ]
    pTVR was defined as HCV RNA < LLOQ at Week 12 after transplant.

  7. Percentage of Participants With HCV RNA < LLOQ at Week 1 [ Time Frame: Week 1 ]
  8. Percentage of Participants With HCV RNA < LLOQ at Week 2 [ Time Frame: Week 2 ]
  9. Percentage of Participants With HCV RNA < LLOQ at Week 4 [ Time Frame: Week 4 ]
  10. Percentage of Participants With HCV RNA < LLOQ at Week 6 [ Time Frame: Week 6 ]
  11. Percentage of Participants With HCV RNA < LLOQ at Week 8 [ Time Frame: Week 8 ]
  12. Percentage of Participants With HCV RNA < LLOQ at Week 12 [ Time Frame: Week 12 ]
  13. Percentage of Participants With HCV RNA < LLOQ at Week 16 [ Time Frame: Week 16 ]
  14. Percentage of Participants With HCV RNA < LLOQ at Week 20 [ Time Frame: Week 20 ]
  15. Percentage of Participants With HCV RNA < LLOQ at Week 24 [ Time Frame: Week 24 ]
  16. HCV RNA Levels and Change From Baseline at Week 1 [ Time Frame: Baseline; Week 1 ]
  17. HCV RNA Levels and Change From Baseline at Week 2 [ Time Frame: Baseline; Week 2 ]
  18. HCV RNA Levels and Change From Baseline at Week 4 [ Time Frame: Baseline; Week 4 ]
  19. HCV RNA Levels and Change From Baseline at Week 6 [ Time Frame: Baseline; Week 6 ]
  20. HCV RNA Levels and Change From Baseline at Week 8 [ Time Frame: Baseline; Week 8 ]
  21. HCV RNA Levels and Change From Baseline at Week 12 [ Time Frame: Baseline; Week 12 ]
  22. 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 ]
    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.

  23. 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 ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to provide written informed consent
  • Chronic genotype 1 and/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, kidney, or corneal.
Contacts and Locations
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Information from the National Library of Medicine

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): NCT02010255


Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
Layout table for investigator information
Study Director: Shampa De-Oertel, PhD Gilead Sciences
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02010255    
Other Study ID Numbers: GS-US-337-0124
2013-002802-30 ( EudraCT Number )
First Posted: December 12, 2013    Key Record Dates
Results First Posted: June 20, 2016
Last Update Posted: November 19, 2018
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis C
Liver Diseases
Digestive System Diseases
Blood-Borne Infections
Communicable Diseases
Infections
Hepatitis, Viral, Human
Virus Diseases
 Flaviviridae Infections
RNA Virus Infections
Hepatitis
Sofosbuvir
Ledipasvir, sofosbuvir drug combination
Ledipasvir
Antiviral Agents
Anti-Infective Agents