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

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis C

Treatments: Drug: SOF/VEL; Drug: LDV/SOF; Drug: RBV; Drug: VOX

Study type: Interventional

Funder types: Industry

Identifiers

NCT02202980

GS-US-337-1468

Details and patient eligibility

About

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.

Enrollment: 273 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

273 participants in 15 patient groups

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

Experimental group

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.

Treatment:

Drug: RBV

Drug: LDV/SOF

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

Experimental group

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.

Treatment:

Drug: RBV

Drug: LDV/SOF

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

Experimental group

Description:

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

Treatment:

Drug: LDV/SOF

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

Experimental group

Description:

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

Treatment:

Drug: LDV/SOF

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

Experimental group

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.

Treatment:

Drug: LDV/SOF

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

Experimental group

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.

Treatment:

Drug: RBV

Drug: LDV/SOF

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

Experimental group

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.

Treatment:

Drug: VOX

Drug: SOF/VEL

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

Experimental group

Description:

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

Treatment:

Drug: VOX

Drug: SOF/VEL

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

Experimental group

Description:

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

Treatment:

Drug: VOX

Drug: SOF/VEL

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

Experimental group

Description:

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

Treatment:

Drug: VOX

Drug: SOF/VEL

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

Experimental group

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.

Treatment:

Drug: VOX

Drug: SOF/VEL

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

Experimental group

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.

Treatment:

Drug: VOX

Drug: SOF/VEL

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

Experimental group

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.

Treatment:

Drug: VOX

Drug: SOF/VEL

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

Experimental group

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.

Treatment:

Drug: VOX

Drug: SOF/VEL

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

Experimental group

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.

Treatment:

Drug: VOX

Drug: SOF/VEL