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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01188772
First received: August 23, 2010
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C Virus
Drug: Sofosbuvir
Drug: Placebo to match sofosbuvir
Drug: PEG
Drug: RBV
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Pegylated Interferon and Ribavirin in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1, and an Open Label Assessment of PSI-7977 in Patients With HCV Genotypes 2 or 3

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period [ Time Frame: Baseline to Week 12 plus 30 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in HCV RNA From Baseline to Week 12 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Rapid Virologic Response at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Rapid virologic response was defined as HCV RNA below the limit of detection (< 15 IU/mL) at Week 4 (Day 29)

  • Percentage of Participants With Complete Early Virologic Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Complete early virologic response was defined as HCV RNA below the limit of detection (< 15 IU/mL) at Week 12

  • Percentage of Participants With Extended Rapid Virologic Response [ Time Frame: Week 4 to Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Virologic Response at the End of Treatment [ Time Frame: Week 48 (genotype 1) or Week 12 (genotype 2/3) ] [ Designated as safety issue: No ]
    End-of-treatment virologic response was defined as HCV RNA below the limit of detection (< 15 IU/mL) at the last on-treatment visit.

  • Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24) [ Time Frame: Post-treatment Weeks 12 and 24 ] [ Designated as safety issue: No ]
    SVR12 and SVR24 were defined as HCV RNA below the limit of detection (< 15 IU/mL) at post-treatment Weeks 12 and 24, respectively.

  • Plasma Pharmacokinetics of GS-331007 (Cmax at Day 8) [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Plasma Pharmacokinetics of GS-331007 (Cmax at Day 15) [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the Cmax at Day 15. 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.

  • Plasma Pharmacokinetics of GS-331007 (Cmax at Day 29) [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the Cmax at Day 29. 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.

  • Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 8) [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the the area under the plasma concentration versus time curve over the dosing interval (AUCtau) 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.

  • Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 15) [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the the area under the plasma concentration versus time curve over the dosing interval (AUCtau) at Day 15. 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.

  • Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 29) [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ] [ Designated as safety issue: No ]
    The pharmacokinetics of sofosbuvir metabolite GS-331007 were analyzed as the the area under the plasma concentration versus time curve over the dosing interval (AUCtau) at Day 29. 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.

  • Percentage of Participants Who Developed Resistance to Sofosbuvir [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    Resistance monitoring was completed in all subjects who received sofosbuvir and who had non-response, viral rebound, virologic breakthrough, or HCV RNA plateaus between Day 0 and Week 24.


Enrollment: 147
Study Start Date: August 2010
Study Completion Date: May 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sofosbuvir 200 mg (Genotype 1)
Participants with genotype 1 HCV infection were randomized to receive sofosbuvir 200 mg (2 x 100 mg tablets)+placebo to match sofosbuvir (2 tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Drug: Sofosbuvir
Sofosbuvir tablets were administered orally once daily.
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
Drug: Placebo to match sofosbuvir
Placebo tablets to match sofosbuvir were administered orally once daily.
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.
Other Name: Pegasys®
Drug: RBV
Ribavirin (RBV) was administered as a tablet orally according to package insert dosing recommendations (Genotype 1: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg; Genotype 2/3: 800 mg).
Other Name: Copegus®
Experimental: Sofosbuvir 400 mg (Genotype 1)
Participants with genotype 1 HCV infection were randomized to receive sofosbuvir 400 mg (4 x 100 mg tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.
Other Name: Pegasys®
Drug: RBV
Ribavirin (RBV) was administered as a tablet orally according to package insert dosing recommendations (Genotype 1: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg; Genotype 2/3: 800 mg).
Other Name: Copegus®
Active Comparator: Placebo (Genotype 1)
Participants with genotype 1 HCV infection were randomized to receive placebo to match sofosbuvir (4 tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Drug: Placebo to match sofosbuvir
Placebo tablets to match sofosbuvir were administered orally once daily.
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.
Other Name: Pegasys®
Drug: RBV
Ribavirin (RBV) was administered as a tablet orally according to package insert dosing recommendations (Genotype 1: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg; Genotype 2/3: 800 mg).
Other Name: Copegus®
Experimental: Sofosbuvir 400 mg (Genotype 2/3)
Participants with genotype 2 or 3 HCV infection received sofosbuvir 400 mg (4 x 100 mg tablets)+PEG+RBV for 12 weeks.
Drug: Sofosbuvir
Sofosbuvir tablets were administered orally once daily.
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.
Other Name: Pegasys®
Drug: RBV
Ribavirin (RBV) was administered as a tablet orally according to package insert dosing recommendations (Genotype 1: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg; Genotype 2/3: 800 mg).
Other Name: Copegus®

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01188772

  Show 23 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Robert H. Hyland, DPhil Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01188772     History of Changes
Other Study ID Numbers: P7977-0422
Study First Received: August 23, 2010
Results First Received: January 6, 2014
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis C Virus
HCV
hepatitis
Genotype 1
Genotype 2
Genotype 3

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferons
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014