Efficacy and Safety of Oral Regimens for the Treatment of Chronic HCV Infection

NCT02202980 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GS-US-337-1468
• Study Type: interventional
• Target: 273
• Locations: 1 country
• Sites: 2

Brief Summary

This study will evaluate the antiviral efficacy, safety, and tolerability of combination therapy with oral regimens for the treatment of chronic hepatitis C virus (HCV) infection.

Conditions

Chronic Hepatitis C

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 (3)

• Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

  Posttreatment Weeks 4 and 24

• Percentage of Participants With Virologic Failure

  Up to Posttreatment Week 24

• Percentage of Participants With HCV RNA < LLOQ While on Treatment by Study Visit

  Weeks 1, 2, 4, 6, 8, 12, 16, 20, and 24 (depending on treatment duration; Week 6 data was not collected for Cohorts 1-3)

Study Arms (15)

LDV/SOF+RBV 24 Weeks (Cohort 1 Group 1)

EXPERIMENTAL

Participants who previously received ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) for ≥ 12 weeks without achieving sustained virologic response at 12 weeks following treatment (SVR12) will receive LDV/SOF+RBV for 24 weeks.

Drug: LDV/SOF; Drug: RBV

LDV/SOF+RBV 12 Weeks (Cohort 1 Group 2)

EXPERIMENTAL

Participants who previously received a sofosbuvir-based regimen without achieving SVR12 were initially enrolled to receive LDV/SOF+RBV for 12 weeks (excluding participants who previously received LDV/SOF+RBV for ≥ 12 weeks). Participants who did not achieve sustained virologic response at 12 weeks were then moved to Cohort 1 Group 1.

Drug: LDV/SOF; Drug: RBV

LDV/SOF 12 Weeks GT2 (Cohort 2 Group 1)

EXPERIMENTAL

Participants with genotype 2 (GT2) HCV infection will receive LDV/SOF FDC for 12 weeks.

Drug: LDV/SOF

LDV/SOF 8 Weeks GT2 (Cohort 2 Group 2)

EXPERIMENTAL

Participants with GT2 HCV infection will receive LDV/SOF FDC for 8 weeks.

Drug: LDV/SOF

LDV/SOF 12 Weeks GT1/GT2/GT4 (Cohort 3 Group 1)

EXPERIMENTAL

Participants with genotypes 1 (GT1), 2 (GT2), or 4 (GT4) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC for 12 weeks.

Drug: LDV/SOF

LDV/SOF+RBV 12 Weeks GT3 (Cohort 3 Group 2)

EXPERIMENTAL

Participants with genotype 3 (GT3) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC plus RBV for 12 weeks.

Drug: LDV/SOF; Drug: RBV

SOF/VEL+VOX 6 Weeks GT1 (Cohort 4)

EXPERIMENTAL

Treatment-naive participants with GT1 HCV infection without cirrhosis will receive VOX only on Day 1 followed by sofosbuvir/velpatasvir (SOF/VEL) + voxilaprevir (VOX) for 6 weeks.

Drug: SOF/VEL; Drug: VOX

SOF/VEL+VOX 4 Weeks GT1 (Cohort 5 Group 1)

EXPERIMENTAL

Treatment-naive participants with GT1 HCV infection without cirrhosis will receive SOF/VEL+VOX for 4 weeks.

Drug: SOF/VEL; Drug: VOX

SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 2)

EXPERIMENTAL

Treatment-naive participants with GT1 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks.

Drug: SOF/VEL; Drug: VOX

SOF/VEL+VOX 6 Weeks GT3 (Cohort 5 Group 3)

EXPERIMENTAL

Treatment-naive participants with GT3 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks.

Drug: SOF/VEL; Drug: VOX

SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 4)

EXPERIMENTAL

Treatment-experienced participants with GT1 HCV infection with cirrhosis who were previously treated with pegylated interferon (Peg-IFN)+RBV will receive SOF/VEL+VOX for 6 weeks.

Drug: SOF/VEL; Drug: VOX

SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 5)

EXPERIMENTAL

Treatment-experienced participants with GT3 HCV infection with cirrhosis who were previously treated with Peg-IFN+RBV will receive SOF/VEL+VOX for 6 weeks.

Drug: SOF/VEL; Drug: VOX

SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 6)

EXPERIMENTAL

Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with non-structural protein (NS3/4A) protease inhibitor (PI) will receive SOF/VEL+VOX for 6 weeks.

Drug: SOF/VEL; Drug: VOX

SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 7)

EXPERIMENTAL

Treatment-experienced participants with GT1 HCV infection with or without cirrhosis who were previously treated with direct-acting antivirals (DAA) will receive SOF/VEL+VOX for 6 weeks.

Drug: SOF/VEL; Drug: VOX

SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 8)

EXPERIMENTAL

Treatment-experienced participants with GT3 HCV infection with or without cirrhosis who were previously treated with DAA will receive SOF/VEL+VOX for 8 weeks.

Drug: SOF/VEL; Drug: VOX

Interventions

LDV/SOF DRUG

90/400 mg FDC tablet administered orally once daily

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

LDV/SOF 12 Weeks GT1/GT2/GT4 (Cohort 3 Group 1); LDV/SOF 12 Weeks GT2 (Cohort 2 Group 1); LDV/SOF 8 Weeks GT2 (Cohort 2 Group 2); LDV/SOF+RBV 12 Weeks (Cohort 1 Group 2); LDV/SOF+RBV 12 Weeks GT3 (Cohort 3 Group 2); LDV/SOF+RBV 24 Weeks (Cohort 1 Group 1)

RBV DRUG

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 (Cohort 1 Group 2); LDV/SOF+RBV 12 Weeks GT3 (Cohort 3 Group 2); LDV/SOF+RBV 24 Weeks (Cohort 1 Group 1)

SOF/VEL DRUG

400/100 mg FDC tablet administered orally once daily

Also known as: Epclusa®, GS-7977/GS-5816

SOF/VEL+VOX 4 Weeks GT1 (Cohort 5 Group 1); SOF/VEL+VOX 6 Weeks GT1 (Cohort 4); SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 2); SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 7); SOF/VEL+VOX 6 Weeks GT3 (Cohort 5 Group 3); SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 4); SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 6); SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 5); SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 8)

VOX DRUG

100 mg tablet administered orally once daily with food

Also known as: GS-9857

SOF/VEL+VOX 4 Weeks GT1 (Cohort 5 Group 1); SOF/VEL+VOX 6 Weeks GT1 (Cohort 4); SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 2); SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 7); SOF/VEL+VOX 6 Weeks GT3 (Cohort 5 Group 3); SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 4); SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 6); SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 5); SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 8)

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent
• Chronic HCV infection
• Cirrhosis determination (liver biopsy may be required)
• Screening laboratory values within specified limits
• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Specific genotype, prior medical history, or concurrent disease as required by the specific study group

You may not qualify if:

• History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
• Pregnant or nursing female, or male with pregnant female partner
• Clinical hepatic decompensation (ie, ascites, encephalopathy or variceal hemorrhage)
• Use of any prohibited concomitant medications

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (2)

Unknown Facility

Auckland, New Zealand

Location

Unknown Facility

Christchurch, New Zealand

Location

Related Publications (3)

• Gane EJ, Svarovskaia ES, Hyland RH, Stamm LM, Osinusi A, Brainard DM, Chodavarapu K, Miller MD, Mo H, Schwabe C. Resistance Analysis of Treatment-Naive and DAA-Experienced Genotype 1 Patients with and without Cirrhosis Who Received Short-Duration Treatment with Sofosbuvir/GS-5816+ GS-9857 [Poster 713]. J Hepatol 2015;62:563A

  RESULT

• Gane EJ, Schwabe C, Hyland RH, Yang Y, Svarovskaia E, Stamm LM, Brainard DM, McHutchison JG, Stedman CA. Efficacy of the Combination of Sofosbuvir, Velpatasvir, and the NS3/4A Protease Inhibitor GS-9857 in Treatment-Naive or Previously Treated Patients With Hepatitis C Virus Genotype 1 or 3 Infections. Gastroenterology. 2016 Sep;151(3):448-456.e1. doi: 10.1053/j.gastro.2016.05.021. Epub 2016 May 27.

  PMID: 27240903 RESULT

• Gane EJ, Hyland RH, Yang Y, Svarovskaia E, Stamm LM, Brainard DM, McHutchison JG, Stedman CAM. Efficacy of Ledipasvir Plus Sofosbuvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2 Infection. Gastroenterology. 2017 May;152(6):1366-1371. doi: 10.1053/j.gastro.2017.01.017. Epub 2017 Jan 27.

  PMID: 28137593 RESULT

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

ledipasvir, sofosbuvir drug combination; sofosbuvir-velpatasvir drug combination; voxilaprevir

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

ClinicalTrialDisclosures@gilead.com

Study Officials

• Gilead Study Director

  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: July 25, 2014
• First Posted: July 29, 2014
• Study Start: August 4, 2014
• Primary Completion: March 16, 2016
• Study Completion: May 9, 2016
• Last Updated: November 16, 2018
• Results First Posted: November 17, 2017

Record last verified: 2017-11

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

NZ (2)