Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Participants With Chronic Genotype 1 HCV Who Participated in a Prior Gilead-Sponsored HCV Treatment Study

• ClinicalTrials.gov Identifier: NCT01987453
• Recruitment Status: Completed
• First Posted: November 19, 2013
• Results First Posted: January 10, 2017
• Last Update Posted: November 19, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV) in participants with chronic genotype 1 hepatitis C virus (HCV) infection who have participated in a prior Gilead-sponsored HCV treatment study, and who did not achieve sustained virologic response (SVR24), defined as HCV RNA < lower limit of quantification (LLOQ) 24 weeks after last dose of study drug (SVR24).

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study To Evaluate The Efficacy And Safety Of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin For 12 or 24 Weeks In Chronic Genotype 1 HCV Infected Subjects Who Participated In A Prior Gilead-Sponsored HCV Treatment Study
• Study Start Date: July 2014
• Actual Primary Completion Date: November 2015
• Actual Study Completion Date: November 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: LDV/SOF+RBV 12 weeks (Group 1); Participants who failed a prior SOF+RBV ± pegylated interferon (Peg-IFN) regimen will receive LDV/SOF FDC plus RBV for 12 weeks.	Drug: LDV/SOF; Tablet(s) administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977; 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) Participants in the LDV/SOF+RBV 24 weeks group will dose adjust RBV according to hemoglobin and renal status as stated in the RBV package insert.
Experimental: LDV/SOF 24 weeks (Group 2); Participants who failed a prior LDV/SOF ± RBV regimen will receive LDV/SOF FDC for 24 weeks.	Drug: LDV/SOF; Tablet(s) administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
Experimental: LDV/SOF+RBV 24 weeks (Group 3); Participants with advanced compensated or decompensated cirrhosis who failed a prior SOF+RBV regimen will receive LDV/SOF FDC plus RBV for 24 weeks.	Drug: LDV/SOF; Tablet(s) administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977; 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) Participants in the LDV/SOF+RBV 24 weeks group will dose adjust RBV according to hemoglobin and renal status as stated in the RBV package insert.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Post-treatment Week 12 ]
   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study treatment.
2. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [ Time Frame: Up to 24 Weeks ]

Secondary Outcome Measures :

1. Percentage of Participants With Sustained Virologic Response (SVR) at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
   SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study treatment, respectively.
2. Percentage of Participants With HCV RNA < LLOQ While on Treatment [ Time Frame: Baseline to Week 24 ]
3. Change in HCV RNA From Baseline [ Time Frame: Baseline to Week 8 ]
4. 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 while on treatment), or
     • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
     • Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)

   • Virologic relapse:

     • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit confirmed with 2 consecutive values or last available posttreatment measurement

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Willing and able to provide written informed consent
• Infection with HCV genotype 1
• HCV RNA > LLOQ at screening
• Participation in a prior Gilead-sponsored study
• Screening laboratory values within defined thresholds
• Use of two effective contraception methods if female of childbearing potential or sexually active male
• Must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator
• Must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments

Key Exclusion Criteria:

• Pregnant or nursing female or male with pregnant female partner
• Co-infection with HIV or hepatitis B virus (HBV)
• Current or prior history of clinical hepatic decompensation (Groups 1 and 2 only)
• Hepatocellular carcinoma (HCC)
• History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, California

Beverly Hills, California, United States, 90210

La Jolla, California, United States, 92037

Los Angeles, California, United States, 90027

Los Angeles, California, United States, 90036

Los Angeles, California, United States, 90069

Oceanside, California, United States, 92056

San Diego, California, United States, 92103

San Francisco, California, United States, 94115

United States, Colorado

Aurora, Colorado, United States, 80045

United States, District of Columbia

Washington, District of Columbia, United States, 20009

United States, Florida

Gainesville, Florida, United States, 32610

Jacksonville, Florida, United States, 32256

Miami, Florida, United States, 33136

Orlando, Florida, United States, 32803

Wellington, Florida, United States, 33414

United States, Georgia

Marietta, Georgia, United States, 30060

United States, Illinois

Chicago, Illinois, United States, 60611

Downers Grove, Illinois, United States, 60515

United States, Indiana

Indianapolis, Indiana, United States, 46237

United States, Kentucky

Bowling Green, Kentucky, United States, 42101

United States, Louisiana

Baton Rouge, Louisiana, United States, 70809

United States, Maryland

Baltimore, Maryland, United States, 21229

United States, Massachusetts

Boston, Massachusetts, United States, 02215

Springfield, Massachusetts, United States, 01105

United States, Minnesota

Minneapolis, Minnesota, United States, 55414

United States, Missouri

Kansas City, Missouri, United States, 64131

United States, New Jersey

Hillsborough, New Jersey, United States, 08844

United States, New Mexico

Albuquerque, New Mexico, United States, 87131

United States, New York

Binghamton, New York, United States, 13903

Manhasset, New York, United States, 11030

New York, New York, United States, 10029

United States, North Carolina

Asheville, North Carolina, United States, 28801

Winston-Salem, North Carolina, United States, 27103

United States, Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Germantown, Tennessee, United States, 38138

United States, Texas

San Antonio, Texas, United States, 78215

United States, Virginia

Norfolk, Virginia, United States, 23502

Richmond, Virginia, United States, 23226

United States, Washington

Seattle, Washington, United States, 98111

Australia, New South Wales

Camperdown, New South Wales, Australia, 2050

France

Clichy, France, 92110

Puerto Rico

San Juan, Puerto Rico, 00927

Spain

Barcelona, Spain, 08028

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

Publications of Results:

Wyles D, Pockros P, Morelli G, Younes Z, Svarovskaia E, Yang JC, Pang PS, Zhu Y, McHutchison JG, Flamm S, Lawitz E. Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens. Hepatology. 2015 Jun;61(6):1793-7. doi: 10.1002/hep.27814. Epub 2015 Apr 27.

Other Publications:

Lawitz E, Pockros PJ, Yang JC, Pang PS, Zhu Y, Svarovskaia E, et al. Ledipasvir/sofosbuvir regimens for the retreatment of patients who failed sofosbuvir-based regimens [Abstract 10868]. Presented at: The 25th Conference of the Asian Pacific Association for the Study of Liver (APASL); 2016 February 20-24; Tokyo, Japan.

Lawitz E, Flamm S, Yang JC, Pang PS, Zhu Y, Svarovskaia E, et al. Retreatment of patients who failed 8 or 12 weeks of ledipasvir/sofosbuvir-based regimens with ledipasvir/sofosbuvir for 24 weeks [Abstract 1627]. Presented at: The 50th Annual Congress of the European Association for the Study of Liver: The International Liver Congress (EASL); 2015 April 22-26; Vienna, Austria

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01987453
• Other Study ID Numbers: GS-US-337-1118; 2014-001245-24 ( EudraCT Number )
• First Posted: November 19, 2013
• Results First Posted: January 10, 2017
• Last Update Posted: November 19, 2018
• Last Verified: November 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

Keywords provided by Gilead Sciences:

genotype 1

Additional relevant MeSH terms:

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir; Antiviral Agents; Anti-Infective Agents