Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders

NCT02120300 | Completed Phase 2 Results

• 1 other identifier: GS-US-334-1274
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 13

Brief Summary

The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with genotypes 1 and 4 hepatitis C virus (HCV) infection and sofosbuvir (SOF) plus ribavirin (RBV) in participants with genotypes 2 and 3 HCV infection. Participants with an inherited bleeding disorder and chronic HCV infection (either monoinfected or HIV-1/HCV coinfected) will be enrolled.

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 Permanently Discontinued Any Study Drug Due to an Adverse Event

  Up to 24 weeks

Secondary Outcomes (6)

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

  Posttreatment Week 4

• Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24

  Weeks 1, 2, 4, 8, 12, 16, 20, and 24

• Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24

  Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24

• Percentage of Participants With Virologic Failure

  Up to Posttreatment Week 24

• Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only)

  Weeks 4, 8, 12, 16, 20, and 24

Study Arms (3)

LDV/SOF GT 1 or 4

EXPERIMENTAL

Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks.

Drug: LDV/SOF

SOF+RBV 12 wks GT 2

EXPERIMENTAL

Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.

Drug: SOF; Drug: RBV

SOF+RBV 24 wks GT 3

EXPERIMENTAL

Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.

Drug: SOF; Drug: RBV

Interventions

LDV/SOF DRUG

90/400 mg FDC tablet administered orally

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

LDV/SOF GT 1 or 4

SOF DRUG

400 mg tablet administered orally once daily

Also known as: Sovaldi®, GS-7977, PSI-7977

SOF+RBV 12 wks GT 2; SOF+RBV 24 wks GT 3

RBV DRUG

Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

SOF+RBV 12 wks GT 2; SOF+RBV 24 wks GT 3

Eligibility Criteria

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

You may qualify if:

• Hemophilia A, B or C, or Von Willebrand's disease
• Chronic genotype 1, 2, 3 or 4 HCV infection
• HCV RNA ≥ 1000 IU/mL at screening
• Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male
• Screening laboratory values within defined thresholds
• For HIV-1/HCV co-infected individuals:
• Suppressed HIV-1 RNA on an antiretroviral (ARV) regimen for at least 6 months prior to screening
• Stable protocol-approved ARV regimen for \> 8 weeks prior to screening
• CD4 T-cell count \> 200 cells/mm\^3 at screening

You may not qualify if:

• Clinically-significant illness (other than HCV, inherited bleeding disorder or HIV-1) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
• Current or prior history of any of the following:
• Hepatic decompensation
• Chronic liver disease of a non-HCV etiology
• Hepatocellular carcinoma (HCC)
• Infection with hepatitis B virus (HBV)
• Pregnant or nursing female
• Prior treatment with inhibitors of nonstructural protein 5A (NS5A) or the NS5B polymerase
• Chronic use of systemically administered immunosuppressive agents
• For HIV-1/HCV co-infected individuals:
• Opportunistic infection within 6 months prior to screening
• Active, serious infection (other than HIV-1 or HCV) requiring parental antibiotics, antivirals or antifungals within 30 days prior to baseline

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (13)

Unknown Facility

Sacramento, California, 95817, United States

Location

Unknown Facility

San Diego, California, 92103-8651, United States

Location

Unknown Facility

San Francisco, California, 94143, United States

Location

Unknown Facility

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

Location

Unknown Facility

Atlanta, Georgia, 30308, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Boston, Massachusetts, 02115, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55407, United States

Location

Unknown Facility

Newark, New Jersey, 07112, United States

Location

Unknown Facility

New York, New York, 10029, United States

Location

Unknown Facility

Rochester, New York, 14621, United States

Location

Unknown Facility

Chapel Hill, North Carolina, 27599-7584, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Walsh C, Workowski K, Terrault N, Sax S, Cohen A, et al. Approved All-Oral Sofosbuvir Regimens Are Safe and Highly Effective in Patients With Hereditary Bleeding Disorders. (2015). Hepatology, 62 (S1): 714A-807A. doi:10.1002/hep.28228

  BACKGROUND

MeSH Terms

Interventions

ledipasvir, sofosbuvir drug combination; Sofosbuvir

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

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

• Robert H Hyland, DPhil

  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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2014
• First Posted: April 22, 2014
• Study Start: April 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: December 6, 2016
• Results First Posted: December 6, 2016

Record last verified: 2016-10

Locations

US (13)