Sofosbuvir in Combination With Pegylated Interferon and Ribavirin and in Treatment-Naive Hepatitis C-infected Patients

Gilead Sciences147 enrolled

Overview

Genotype 1: Participants with genotype 1 hepatitis C (HCV) infection were randomized to receive sofosbuvir (GS-7977; PSI-7977) 200 mg or 400 mg, or matching placebo, plus pegylated interferon alfa 2a (PEG) and ribavirin (RBV) for 12 weeks, followed by PEG+RBV for an up to an additional 36 weeks. Randomization was stratified by IL28B status (CC, CT, TT) and HCV RNA level (\< 800,000 IU/ml or ≥ 800,000 IU/ml) at baseline. Participants were randomized in a 2:2:1 manner; those who achieved an extended rapid virologic response (eRVR) (HCV RNA \< lower limit of detection \[15 IU/mL\] from Weeks 4 through 12) received an additional 12 weeks of PEG+RBV. Subjects not achieving eRVR received an additional 36 weeks of PEG+RBV. Genotype 2 and 3: Participants with genotype 2 or 3 hepatitis C (HCV) received sofosbuvir 400 mg plus PEG+RBV for 12 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

147

Conditions

Hepatitis C Virus

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males or females aged 18 to 70 years, inclusive, at screening * Documented chronic genotype 1, 2, or 3 HCV infection * No previous treatment with HCV antiviral mediations * Body mass index (BMI) of greater than 18 kg/m2, but not exceeding 36 kg/m2. * Liver biopsy obtained within 3 years prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic as judged by a local pathologist * Willing to refrain from beginning any new exercise regimens during the first 3 months of the study * Fasting blood glucose ≤ 300 mg/dl and/or glycosylated hemoglobin (HbA1c) ≤ 8 * History of hypertension only if managed effectively on a stable regimen of two or fewer antihypertensives for at least three (3) months prior to screening Exclusion Criteria: * Females who were breastfeeding * Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study * Positive test at Screening for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab. * History of any other clinically significant chronic liver disease * Treatment with herbal/natural remedies with antiviral activity within 30 days prior to baseline. * Significant history of immunologically mediated disease, cardiac or pulmonary disease, seizure disorder or anticonvulsant use * History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease * Use of medications associated with QT prolongation within 30 days prior to dosing * Screening electrocardiogram (ECG) QTc value greater than 450 ms and/or clinically significant ECG findings * Personal or family history of Torsade de pointes. * Positive results for drugs of abuse test at screening * Abnormal hematological and biochemical parameters, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 5 times the upper limit of the normal range (ULN) * History of major organ transplantation with an existing functional graft * History of uncontrolled thyroid disease or abnormal thyroid-stimulating hormone (TSH) levels at screening * Clinically significant drug allergy to nucleoside/nucleotide analogs * History or current evidence of psychiatric illness, immunologic disorder, pulmonary, cardiac disease, seizure disorder, cancer or history of malignancy that in the opinion of the investigator makes the patient unsuitable for the study * History of systemic antineoplastic or immunomodulatory treatment within 6 months prior to dosing, or the expectation of such treatment during the study

Locations (23)

Alabama Liver and Digestive Specialists

Montgomery, Alabama, United States

Advanced Clinical Research Institute

Anaheim, California, United States

SCTI Research Foundation

Coronado, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Dr. Jay Lalezari

San Francisco, California, United States

Dr. Natalie Bzowej

San Francisco, California, United States

Dr. David Nelson

Gainesville, Florida, United States

Orlando Immunology Center

Orlando, Florida, United States

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

...and 13 more locations

Outcomes

Primary Outcomes

Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period

Adverse events (AEs) occurring during the sofosbuvir treatment period and for 30 days following the last dose of sofosbuvir were summarized across the participant population. A participant was counted once if they had a qualifying event.

Time frame: Baseline to Week 12 plus 30 days

Secondary Outcomes

Change in HCV RNA From Baseline to Week 12

Time frame: Baseline to Week 12

Percentage of Participants With Rapid Virologic Response at Week 4

Rapid virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 4 (Day 29)

Time frame: Week 4

Percentage of Participants With Complete Early Virologic Response at Week 12

Complete early virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 12

Time frame: Week 12

Percentage of Participants With Extended Rapid Virologic Response

Extended rapid virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at Week 4 (Day 29) which was maintained through Week 12.

Time frame: Week 4 to Week 12

Percentage of Participants With Virologic Response at the End of Treatment

End-of-treatment virologic response was defined as HCV RNA below the limit of detection (\< 15 IU/mL) at the last on-treatment visit.

Time frame: Week 48 (genotype 1) or Week 12 (genotype 2/3)

Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)

SVR12 and SVR24 were defined as HCV RNA below the limit of detection (\< 15 IU/mL) at post-treatment Weeks 12 and 24, respectively.

Time frame: Post-treatment Weeks 12 and 24

Plasma Pharmacokinetics of GS-331007 (Cmax at Day 8)

The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the maximum observed concentration of drug in plasma (Cmax) at Day 8. Blood samples were collected at 1, 2, and 4 hours postdose for all participants, and at 8 and 12 hours postdose for participants enrolled at selected sites.