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

Primary Purpose

Chronic Hepatitis C

Status
Completed
Phase
Phase 2
Locations
New Zealand
Study Type
Interventional
Intervention
LDV/SOF
RBV
SOF/VEL
VOX
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

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

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

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

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

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

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

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

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

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 GT3 (Cohort 5 Group 5)

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

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

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

Arm Description

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.

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.

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

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

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.

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

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.

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

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

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

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event

Secondary Outcome Measures

Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Percentage of Participants With Virologic Failure
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.
Percentage of Participants With HCV RNA < LLOQ While on Treatment by Study Visit

Full Information

First Posted
July 25, 2014
Last Updated
October 19, 2018
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02202980
Brief Title
Efficacy and Safety of Oral Regimens for the Treatment of Chronic HCV Infection
Acronym
LEPTON
Official Title
A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy and Safety of Oral Regimens for the Treatment of Chronic HCV Infection
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
August 4, 2014 (Actual)
Primary Completion Date
March 16, 2016 (Actual)
Study Completion Date
May 9, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
273 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LDV/SOF+RBV 24 Weeks (Cohort 1 Group 1)
Arm Type
Experimental
Arm Description
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.
Arm Title
LDV/SOF+RBV 12 Weeks (Cohort 1 Group 2)
Arm Type
Experimental
Arm Description
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.
Arm Title
LDV/SOF 12 Weeks GT2 (Cohort 2 Group 1)
Arm Type
Experimental
Arm Description
Participants with genotype 2 (GT2) HCV infection will receive LDV/SOF FDC for 12 weeks.
Arm Title
LDV/SOF 8 Weeks GT2 (Cohort 2 Group 2)
Arm Type
Experimental
Arm Description
Participants with GT2 HCV infection will receive LDV/SOF FDC for 8 weeks.
Arm Title
LDV/SOF 12 Weeks GT1/GT2/GT4 (Cohort 3 Group 1)
Arm Type
Experimental
Arm Description
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.
Arm Title
LDV/SOF+RBV 12 Weeks GT3 (Cohort 3 Group 2)
Arm Type
Experimental
Arm Description
Participants with genotype 3 (GT3) HCV infection and extrahepatic manifestations of chronic HCV infection will receive LDV/SOF FDC plus RBV for 12 weeks.
Arm Title
SOF/VEL+VOX 6 Weeks GT1 (Cohort 4)
Arm Type
Experimental
Arm Description
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.
Arm Title
SOF/VEL+VOX 4 Weeks GT1 (Cohort 5 Group 1)
Arm Type
Experimental
Arm Description
Treatment-naive participants with GT1 HCV infection without cirrhosis will receive SOF/VEL+VOX for 4 weeks.
Arm Title
SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 2)
Arm Type
Experimental
Arm Description
Treatment-naive participants with GT1 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks.
Arm Title
SOF/VEL+VOX 6 Weeks GT3 (Cohort 5 Group 3)
Arm Type
Experimental
Arm Description
Treatment-naive participants with GT3 HCV infection with cirrhosis will receive SOF/VEL+VOX for 6 weeks.
Arm Title
SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 4)
Arm Type
Experimental
Arm Description
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.
Arm Title
SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 5)
Arm Type
Experimental
Arm Description
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.
Arm Title
SOF/VEL+VOX 8 Weeks GT1 (Cohort 5 Group 6)
Arm Type
Experimental
Arm Description
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.
Arm Title
SOF/VEL+VOX 6 Weeks GT1 (Cohort 5 Group 7)
Arm Type
Experimental
Arm Description
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.
Arm Title
SOF/VEL+VOX 8 Weeks GT3 (Cohort 5 Group 8)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
LDV/SOF
Other Intervention Name(s)
Harvoni®, GS-5885/GS-7977
Intervention Description
90/400 mg FDC tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
SOF/VEL
Other Intervention Name(s)
Epclusa®, GS-7977/GS-5816
Intervention Description
400/100 mg FDC tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
VOX
Other Intervention Name(s)
GS-9857
Intervention Description
100 mg tablet administered orally once daily with food
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Time Frame
Posttreatment Week 12
Title
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description
SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Time Frame
Posttreatment Weeks 4 and 24
Title
Percentage of Participants With Virologic Failure
Description
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.
Time Frame
Up to Posttreatment Week 24
Title
Percentage of Participants With HCV RNA < LLOQ While on Treatment by Study Visit
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: 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 Key Exclusion Criteria: 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 Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Auckland
Country
New Zealand
City
Christchurch
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
http://www.gilead.com/research/disclosure-and-transparency
Citations:
Citation
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
Results Reference
result
PubMed Identifier
27240903
Citation
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.
Results Reference
result
PubMed Identifier
28137593
Citation
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.
Results Reference
result

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

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