Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients

NCT01054729 | Completed Phase 2 Results

• 1 other identifier: P7977-0221
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 7

Brief Summary

Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Placebo tablets were administered to participants receiving 100 mg active sofosbuvir (3 placebo tablets) and 200 mg active sofosbuvir (2 placebo tablets) in order to maintain the study blind. Participants received sofosbuvir/matching placebo from Day 0 to 27. Participants also received treatment with PEG+RBV starting on Day 0 of the study which continued for 48 weeks. Participants were evaluated for sustained virologic response (SVR) for an additional 24 weeks following completion of study treatment.

Conditions

Hepatitis C

Keywords

Chronic Hepatitis C infection Genotype 1; HCV; GT1; GT 1

Outcome Measures

Primary Outcomes (1)

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

  Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.

  Baseline to Week 4

Secondary Outcomes (16)

• Change in Circulating HCV RNA at Week 4

  Baseline to Week 4

• Percentage of Participants With Rapid Virologic Response at Week 4

  Week 4

• Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment

  Post-treatment Weeks 12 and 24

• Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0

  Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

• Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27

  Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

Study Arms (4)

Sofosbuvir 100 mg+PEG+RBV

EXPERIMENTAL

Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

Drug: Sofosbuvir; Drug: PEG; Drug: RBV

Sofosbuvir 200 mg+PEG+RBV

EXPERIMENTAL

Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

Drug: Sofosbuvir; Drug: PEG; Drug: RBV

Sofosbuvir 400 mg+PEG+RBV

EXPERIMENTAL

Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

Drug: Sofosbuvir; Drug: PEG; Drug: RBV

Placebo+PEG+RBV

ACTIVE COMPARATOR

Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

Drug: Placebo; Drug: PEG; Drug: RBV

Interventions

Sofosbuvir DRUG

Sofosbuvir tablet(s) administered orally once daily

Also known as: Sovaldi®, GS-7977, PSI-7977

Sofosbuvir 100 mg+PEG+RBV; Sofosbuvir 200 mg+PEG+RBV; Sofosbuvir 400 mg+PEG+RBV

Placebo DRUG

Placebo to match sofosbuvir administered orally once daily

Placebo+PEG+RBV

PEG DRUG

Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.

Also known as: Pegasys®

Placebo+PEG+RBV; Sofosbuvir 100 mg+PEG+RBV; Sofosbuvir 200 mg+PEG+RBV; Sofosbuvir 400 mg+PEG+RBV

RBV DRUG

Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).

Also known as: Copegus®

Placebo+PEG+RBV; Sofosbuvir 100 mg+PEG+RBV; Sofosbuvir 200 mg+PEG+RBV; Sofosbuvir 400 mg+PEG+RBV

Eligibility Criteria

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

You may qualify if:

• Treatment-naive males and females, 18-65 years of age
• Genotype 1 HCV infection
• Negative pregnancy test for females of childbearing age
• Females of childbearing age and males with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin

You may not qualify if:

• Hepatitis B or HIV infection
• Pregnant or breast feeding females or male partners of pregnant females
• Previous interferon or ribavirin-based therapy or investigational anti-HCV agent
• History or evidence of medical condition associated with chronic liver disease other than HCV

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (7)

Quest Clinical Research

San Francisco, California, 94115, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Alamo Medical Research Center

San Antonio, Texas, 78215, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Fundacion de Investigacion de Diego

Santurce, Puerto Rico, 00909, Puerto Rico

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Sofosbuvir; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Robert H. Hyland, DPhil

  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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2010
• First Posted: January 22, 2010
• Study Start: January 1, 2010
• Primary Completion: April 1, 2010
• Study Completion: August 1, 2011
• Last Updated: April 17, 2014
• Results First Posted: February 19, 2014

Record last verified: 2014-03

Locations

US (6); PR (1)