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

NCT01938430 | Completed Phase 2 Results DMC

• 1 other identifier: GS-US-337-0123
• Study Type: interventional
• Target: 339
• Locations: 1 country
• Sites: 30

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.

Conditions

Chronic HCV Infection

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

  SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

  Posttreatment Week 12

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event

  Up to 24 weeks

Secondary Outcomes (23)

• Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2)

  Posttreatment Week 2

• Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)

  Posttreatment Week 4

• Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8)

  Posttreatment Week 8

• Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24)

  Posttreatment Week 24

• Percentage of Participants With Virologic Failure

  Up to Posttreatment Week 24

Study Arms (14)

Cohort A, Group 1 (12 wk): CPT Class B (7-9)

EXPERIMENTAL

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; Drug: RBV

Cohort A, Group 1 (24 wk): CPT Class B (7-9)

EXPERIMENTAL

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; Drug: RBV

Cohort A, Group 2 (12 wk): CPT Class C (10-12)

EXPERIMENTAL

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; Drug: RBV

Cohort A, Group 2 (24 wk): CPT Class C (10-12)

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 3 (12 wk): F0-F3 Fibrosis

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 3 (24 wk): F0-F3 Fibrosis

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 4 (12 wk): CPT Class A (5-6)

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 4 (24 wk): CPT Class A (5-6)

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 5 (12 wk): CPT Class B (7-9)

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 5 (24 wk): CPT Class B (7-9)

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 6 (12 wk): CPT Class C (10-12)

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 6 (24 wk): CPT Class C (10-12)

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 7 (12 wk): FCH

EXPERIMENTAL

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; Drug: RBV

Cohort B, Group 7 (24 wk): FCH

EXPERIMENTAL

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; Drug: RBV

Interventions

LDV/SOF DRUG

LDV/SOF FDC tablet administered orally once daily

Also known as: Harvoni®, GS-5885/GS-7977

Cohort A, Group 1 (12 wk): CPT Class B (7-9); Cohort A, Group 1 (24 wk): CPT Class B (7-9); Cohort A, Group 2 (12 wk): CPT Class C (10-12); Cohort A, Group 2 (24 wk): CPT Class C (10-12); Cohort B, Group 3 (12 wk): F0-F3 Fibrosis; Cohort B, Group 3 (24 wk): F0-F3 Fibrosis; Cohort B, Group 4 (12 wk): CPT Class A (5-6); Cohort B, Group 4 (24 wk): CPT Class A (5-6); Cohort B, Group 5 (12 wk): CPT Class B (7-9); Cohort B, Group 5 (24 wk): CPT Class B (7-9); Cohort B, Group 6 (12 wk): CPT Class C (10-12); Cohort B, Group 6 (24 wk): CPT Class C (10-12); Cohort B, Group 7 (12 wk): FCH; Cohort B, Group 7 (24 wk): FCH

RBV DRUG

RBV tablets administered orally in a divided daily dose

Cohort A, Group 1 (12 wk): CPT Class B (7-9); Cohort A, Group 1 (24 wk): CPT Class B (7-9); Cohort A, Group 2 (12 wk): CPT Class C (10-12); Cohort A, Group 2 (24 wk): CPT Class C (10-12); Cohort B, Group 3 (12 wk): F0-F3 Fibrosis; Cohort B, Group 3 (24 wk): F0-F3 Fibrosis; Cohort B, Group 4 (12 wk): CPT Class A (5-6); Cohort B, Group 4 (24 wk): CPT Class A (5-6); Cohort B, Group 5 (12 wk): CPT Class B (7-9); Cohort B, Group 5 (24 wk): CPT Class B (7-9); Cohort B, Group 6 (12 wk): CPT Class C (10-12); Cohort B, Group 6 (24 wk): CPT Class C (10-12); Cohort B, Group 7 (12 wk): FCH; Cohort B, Group 7 (24 wk): FCH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (30)

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Phoenix, Arizona, 85054, United States

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San Diego, California, 92103, United States

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San Francisco, California, 94143, United States

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Aurora, Colorado, 80045, United States

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Washington D.C., District of Columbia, 20007, United States

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Jacksonville, Florida, 32224, United States

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Miami, Florida, 33136, United States

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Chicago, Illinois, 60611, United States

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Indianapolis, Indiana, 46202, United States

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Kansas City, Kansas, 66160, United States

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Lutherville, Maryland, 21093, United States

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Boston, Massachusetts, 02215, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48202, United States

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Minneapolis, Minnesota, 55455, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63110, United States

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New York, New York, 10016, United States

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New York, New York, 10032, United States

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Chapel Hill, North Carolina, 27599, United States

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Durham, North Carolina, 27710, United States

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Cleveland, Ohio, 44195, United States

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Portland, Oregon, 97239, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Dallas, Texas, 75246, United States

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Murray, Utah, 84107, United States

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Richmond, Virginia, 23219, United States

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Seattle, Washington, 98101, United States

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Seattle, Washington, 98104, United States

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Related Publications (2)

• 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.

  PMID: 26891418 DERIVED

• 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.

  PMID: 25985734 DERIVED

MeSH Terms

Interventions

ledipasvir, sofosbuvir drug combination

Limitations and Caveats

There were no limitations affecting the analysis or results.

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Shampa De-Oertel, PhD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: September 10, 2013
• Study Start: September 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: March 1, 2015
• Last Updated: November 16, 2018
• Results First Posted: April 15, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (30)