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

NCT ID: NCT01938430

Last Updated: 2018-11-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

339 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Study Completion Date

2015-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic HCV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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.

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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)

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

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

Group Type EXPERIMENTAL

LDV/SOF

Intervention Type DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type DRUG

RBV tablets administered orally in a divided daily dose

Interventions

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LDV/SOF

LDV/SOF FDC tablet administered orally once daily

Intervention Type DRUG

RBV

RBV tablets administered orally in a divided daily dose

Intervention Type DRUG

Other Intervention Names

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Harvoni® GS-5885/GS-7977

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shampa De-Oertel, PhD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Phoenix, Arizona, United States

Site Status

San Diego, California, United States

Site Status

San Francisco, California, United States

Site Status

Aurora, Colorado, United States

Site Status

Washington D.C., District of Columbia, United States

Site Status

Jacksonville, Florida, United States

Site Status

Miami, Florida, United States

Site Status

Chicago, Illinois, United States

Site Status

Indianapolis, Indiana, United States

Site Status

Kansas City, Kansas, United States

Site Status

Lutherville, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

Ann Arbor, Michigan, United States

Site Status

Detroit, Michigan, United States

Site Status

Minneapolis, Minnesota, United States

Site Status

Rochester, Minnesota, United States

Site Status

St Louis, Missouri, United States

Site Status

New York, New York, United States

Site Status

New York, New York, United States

Site Status

Chapel Hill, North Carolina, United States

Site Status

Durham, North Carolina, United States

Site Status

Cleveland, Ohio, United States

Site Status

Portland, Oregon, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Pittsburgh, Pennsylvania, United States

Site Status

Dallas, Texas, United States

Site Status

Murray, Utah, United States

Site Status

Richmond, Virginia, United States

Site Status

Seattle, Washington, United States

Site Status

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Welzel TM, Reddy KR, Flamm SL, Denning J, Lin M, Hyland R, Pang PS, McHutchison JG, Charlton M, Everson GT, Zeuzem S, Afdhal N. On-treatment HCV RNA in patients with varying degrees of fibrosis and cirrhosis in the SOLAR-1 trial. Antivir Ther. 2016;21(6):541-546. doi: 10.3851/IMP3037. Epub 2016 Feb 18.

Reference Type DERIVED
PMID: 26891418 (View on PubMed)

Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown RS Jr, Fried MW, Terrault NA, O'Leary JG, Vargas HE, Kuo A, Schiff E, Sulkowski MS, Gilroy R, Watt KD, Brown K, Kwo P, Pungpapong S, Korenblat KM, Muir AJ, Teperman L, Fontana RJ, Denning J, Arterburn S, Dvory-Sobol H, Brandt-Sarif T, Pang PS, McHutchison JG, Reddy KR, Afdhal N; SOLAR-1 Investigators. Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease. Gastroenterology. 2015 Sep;149(3):649-59. doi: 10.1053/j.gastro.2015.05.010. Epub 2015 May 15.

Reference Type DERIVED
PMID: 25985734 (View on PubMed)

Other Identifiers

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GS-US-337-0123

Identifier Type: -

Identifier Source: org_study_id

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