Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects

NCT01726517 | Completed Phase 2 Results

• 1 other identifier: GS-US-337-0118
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV), administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive, and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.

Conditions

Chronic Hepatitis C Virus

Keywords

HCV genotype 1 (GT-1); HCV; Sustained Virologic Response; Direct Acting Antiviral; Combination Therapy; GS-7977; GS-5885; Ribavirin; Open Label; Sofosbuvir; Treatment-Naïve; Protease Inhibitors; PI

Outcome Measures

Primary Outcomes (2)

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

  SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after stopping study treatment.

  Posttreatment Week 12

• Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)

  The number of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was summarized.

  Baseline to Week 12

Secondary Outcomes (2)

• Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24)

  Posttreatment Weeks 2, 4, 8, and 24

• Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse

  Baseline to Posttreatment Week 24

Study Arms (5)

LDV/SOF 8 Weeks (TN)

EXPERIMENTAL

Treatment-naive (TN) participants will be randomized to receive LDV/SOF for 8 weeks.

Drug: LDV/SOF

LDV/SOF+RBV 8 Weeks (TN)

EXPERIMENTAL

Treatment-naive participants will be randomized to receive LDV/SOF plus RBV for 8 weeks.

Drug: LDV/SOF; Drug: RBV

LDV/SOF 12 Weeks (TN)

EXPERIMENTAL

Treatment-naive participants will be randomized to receive LDV/SOF for 12 weeks.

Drug: LDV/SOF

LDV/SOF 12 Weeks (TE)

EXPERIMENTAL

Treatment-experienced (TE) participants (had virologic failure following prior therapy with a protease-inhibitor \[PI\]+pegylated interferon \[PEG\]+RBV regimen) will be randomized to receive LDV/SOF for 12 weeks.

Drug: LDV/SOF

LDV/SOF+RBV 12 Weeks (TE)

EXPERIMENTAL

Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) will be randomized to receive LDV/SOF plus RBV for 12 weeks.

Drug: LDV/SOF; Drug: RBV

Interventions

LDV/SOF DRUG

LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily

Also known as: Harvoni®

LDV/SOF 12 Weeks (TE); LDV/SOF 12 Weeks (TN); LDV/SOF 8 Weeks (TN); LDV/SOF+RBV 12 Weeks (TE); LDV/SOF+RBV 8 Weeks (TN)

RBV DRUG

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)

LDV/SOF+RBV 12 Weeks (TE); LDV/SOF+RBV 8 Weeks (TN)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, with chronic genotype 1 HCV infection
• HCV RNA equal to or greater than 10,000 IU/mL at screening
• Cirrhosis determination; a liver biopsy may be required
• Screening laboratory values within defined thresholds
• Use of two effective contraception methods if female of childbearing potential or sexually active male

You may not qualify if:

• Pregnant or nursing female or male with pregnant female partner
• Current or prior history of clinical hepatic decompensation
• Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
• Chronic use of systemic immunosuppressive agents
• History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Unknown Facility

San Antonio, Texas, 78215, United States

Location

Related Publications (1)

• Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5.

  PMID: 24209977 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Rob Hyland

  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: November 10, 2012
• First Posted: November 15, 2012
• Study Start: October 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: January 1, 2014
• Last Updated: November 16, 2018
• Results First Posted: November 17, 2014

Record last verified: 2014-11

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 (1)