GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Hepatitis C, Chronic

Treatments: Drug: GS-5885; Drug: placebo to match RBV; Drug: placebo to match tegobuvir; Drug: tegobuvir; Drug: GS-9451; Drug: Ribavirin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01435226

GS-US-248-0131

Details and patient eligibility

About

This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared with GS-5885, GS-9451 with Tegobuvir or RBV in Treatment-Experienced Subjects with Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection.

Enrollment: 170 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18 years with chronic HCV infection

• Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed

• Monoinfection with HCV genotype (GT) 1a or 1b

• HCV RNA ≥ 104 IU/mL at screening

• Prior treatment and adherence with one course of pegylated interferon alfa and RBV

• The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.

• Body mass index (BMI) 18-40 kg/m2 inclusive

• Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)

  ≤ 450 msec for males and ≤ 470 msec for females.

• Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.

Exclusion criteria

• Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
• History of significant cardiac disease
• Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
• Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
• Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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170 participants in 3 patient groups

Arm 1

Active Comparator group

Description:

GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID

Treatment:

Drug: GS-5885

Drug: tegobuvir

Drug: GS-9451

Drug: Ribavirin

Arm 2

Active Comparator group

Description:

GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID

Treatment:

Drug: GS-5885

Drug: tegobuvir

Drug: GS-9451

Drug: placebo to match RBV

Arm 3

Active Comparator group

Description:

GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID

Treatment:

Drug: GS-5885

Drug: GS-9451

Drug: placebo to match tegobuvir

Drug: Ribavirin