Open-Labeled Study of PSI-7977 and RBV With and Without PEG-IFN in Treatment-Naïve Patients With HCV GT2 or GT3

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01260350
First received: December 13, 2010
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

To assess safety and tolerability of PSI-7977 400 mg with and without ribavirin (RBV) and/or with and without pegylated interferon alfa-2a (PEG-IFN) in subjects with hepatitis C (HCV) genotypes 1, 2 or 3.


Condition Intervention Phase
Chronic Hepatitis C Infection
Drug: PSI-7977
Drug: Ribavirin
Drug: Pegylated-Interferon
Drug: GS-5885
Drug: GS-9669
Drug: Sofosbuvir/GS-5885 400/90 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open-Labeled Exploratory Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 400 mg and Ribavirin for 12 Weeks With and Without Pegylated Interferon in Treatment-Naïve Patients With Chronic HCV Infection Genotype 2 or Genotype 3

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: 8 or 12 weeks ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of sofosbuvir 400 mg for 8 or 12 weeks, administered with and without ribavirin and/or pegylated interferon alfa-2a (PEG-IFN) in subjects with HCV genotypes 1, 2 or 3, with and without GS-5885 or GS-9669 in subjects with genotype 1 and also of sofosbuvir/GS-5885 FDC for 6 or 12 weeks, administered with and without ribavirin, in subjects with HCV genotype 1, 2 or 3.


Secondary Outcome Measures:
  • HCV RNA [ Time Frame: 6, 8, or 12 weeks ] [ Designated as safety issue: No ]
    To evaluate the change in circulating HCV RNA in subjects over 6, 8, or 12 weeks of dosing with sofosbuvir or sofosbuvir/GS-5885 administered with or without ribavirin and/or PEG-IFN or GS-5885 or GS-9669

  • HCV RNA [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To evaluate the proportion of subjects who have HCV RNA below the lower limit of quantitation (LLOQ) and below the limit of detection (LOD) at various time points in the study

  • Sustained Virologic Response (SVR) [ Time Frame: SVR 12 ] [ Designated as safety issue: No ]
    To evaluate the sustained virologic response at 12 weeks (SVR12) following completion of all treatment

  • Resistance [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To evaluate the emergence of HCV resistance against sofosbuvir, GS-5885 or GS-9669

  • Duration of PEG-IFN therapy [ Time Frame: SVR 12 ] [ Designated as safety issue: No ]
    To explore the effects of the duration of PEG-IFN therapy on safety, tolerability, emergence of resistance, viral kinetics, and SVR12

  • Pharmacokinetics [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    To characterize the steady-state plasma pharmacokinetics of the GS-331007 metabolite of sofosbuvir


Enrollment: 292
Study Start Date: December 2010
Study Completion Date: December 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: PSI-7977 and RBV
PSI-7977 400 mg QD and weight-based RBV 12 weeks in GT 2/3 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Experimental: Arm 2: PSI-7977 and RBV with PEG-IFN
PSI-7977 400 mg QD and weight-based RBV for 12 weeks with 4 weeks of PEG-IFN in GT-2/3 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: Pegylated-Interferon
Other Names:
  • Pegylated-Interferon
  • PEG-IFN
Experimental: Arm 3: PSI-7977 and RBV with PEG-IFN
PSI-7977 400 mg QD and weight-based RBV for 12 weeks with 8 weeks PEG-IFN in GT-2/3 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: Pegylated-Interferon
Other Names:
  • Pegylated-Interferon
  • PEG-IFN
Experimental: Arm 4: PSI-7977 and RBV with PEG-IFN
PSI-7977 400 mg QD and weight-based RBV with 12 weeks PEG-IFN in GT-2/3 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: Pegylated-Interferon
Other Names:
  • Pegylated-Interferon
  • PEG-IFN
Experimental: Arm 5: PSI-7977 monotherapy
PSI-7977 400 mg QD monotherapy for 12 weeks in GT-2/3 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Experimental: Arm 6: PSI-7977 and RBV with PEG-IFN
PSI-7977 400 mg QD with weight-based RBV and PEG-IFN for 8 weeks in GT-2/3 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: Pegylated-Interferon
Other Names:
  • Pegylated-Interferon
  • PEG-IFN
Experimental: Arm 7: PSI-7977 with RBV
PSI-7977 400 mg QD with weight-based RBV for 12 weeks in GT-1 null responders
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Experimental: Arm 8: PSI-7977 and RBV
PSI-7977 400 mg QD and weight-based RBV for 12 weeks in GT-1 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Experimental: Arm 9: PSI-7977 and RBV
PSI-7977 400 mg QD and weight-based RBV for 12 weeks in GT 2/3 treatment experienced subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Experimental: Arm 10: PSI-7977 and RBV
PSI-7977 400 mg QD and weight-based RBV for 8 weeks in GT 2/3 treatment naive patients
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Experimental: Arm 11: PSI-7977 with RBV
PSI-7977 400 mg QD and RBV 800 mg (split dose) for 12 weeks in GT 2/3 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Experimental: Arm 12: PSI-7977, RBV, GS-5885
PSI-7977 400 mg QD and weight-based RBV and GS-5885 for 12 weeks in GT-1 null responders
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: GS-5885
Other Name: GS-5885
Experimental: Arm 13: PSI-7977, RBV, GS-5885
PSI-7977 400 mg QD, weight-based RBV and GS-5885 for 12 weeks in GT-1 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: GS-5885
Other Name: GS-5885
Experimental: Arm 14: PSI-7977, RBV, GS-9669
PSI-7977 400 mg QD, weight-based RBV and GS-9669 for 12 weeks in GT-1 null responders
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: GS-9669
Other Name: GS-9669
Experimental: Arm 15: PSI-7977, RBV, GS-9669
PSI-7977 400 mg QD, weight-based RBV and GS-9669 for 12 weeks in GT-1 treatment naive subjects
Drug: PSI-7977
Other Names:
  • Sofosbuvir
  • PSI-7977
  • GS-7977
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: GS-9669
Other Name: GS-9669
Experimental: Arm 16: Sofosbuvir/GS-5885 FDC
Sofosbuvir/GS-5885 FDC for 12 weeks in GT-1 prior null responders with cirrhosis
Drug: Sofosbuvir/GS-5885 400/90 mg
FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily
Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Arm 17: Sofosbuvir/GS-5885 FDC and RBV
Sofosbuvir/GS-5885 FDC and weight-based RBV for 12 weeks in GT-1 prior null responders with cirrhosis
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: Sofosbuvir/GS-5885 400/90 mg
FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily
Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Arm 18: Sofosbuvir/GS-5885 FDC
Sofosbuvir/GS-5885 FDC for 12 weeks in GT-2/3 treatment naive subjects
Drug: Sofosbuvir/GS-5885 400/90 mg
FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily
Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Arm 19: Sofosbuvir/GS-5885 FDC
Sofosbuvir/GS-5885 FDC for 12 weeks in GT-2/3 treatment experienced subjects
Drug: Sofosbuvir/GS-5885 400/90 mg
FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily
Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Arm 20: Sofosbuvir/GS-5885 FDC and RBV
Sofosbuvir/GS-5885 FDC and weight-based RBV for 12 weeks in GT-1 Hemophiliacs
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: Sofosbuvir/GS-5885 400/90 mg
FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily
Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Arm 21: Sofosbuvir/GS-5885 FDC and RBV
Sofosbuvir/GS-5885 FDC and weight-based RBV for 6 weeks in GT-1 treatment naive subjects
Drug: Ribavirin
Other Names:
  • Ribavirin
  • RBV
Drug: Sofosbuvir/GS-5885 400/90 mg
FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily
Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Arm 22: Sofosbuvir/GS-5885 FDC
Sofosbuvir/GS-5885 FDC for 6 weeks in GT-1 treatment naive subjects
Drug: Sofosbuvir/GS-5885 400/90 mg
FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily
Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.

Detailed Description:

Part 1: PSI-7977 400 mg QD with weight-based RBV for 12 weeks. Subjects will be randomized in equal proportions to: no PEG-IFN (Arm 1), PEG-IFN for 4 weeks (Arm 2), PEG-IFN for 8 weeks (Arm 3), or PEG-IFN for 12 weeks (Arm 4); Part 2: HCV GT 2/3 patients receive PSI-7977 400 mg QD monotherapy for 12 weeks (Arm 5), or PSI-7977 400 mg QD with PEG-IFN and weight-based RBV for 8 weeks (Arm 6), and HCV GT1 null-responders receive PSI-7977 400 mg QD with weight-based RBV for 12 weeks (Arm 7); Part 3: HCV GT-1 treatment naive (Arm 8) or HCV GT 2/3 treatment experienced subjects (Arm 9) receive PSI-7977 400 mg QD in combination with weight-based RBV for 12 weeks; Part 4: HCV GT-2/3 treatment naive subjects receive PSI-7977 400 mg QD with weight-based RBV for 8 weeks (Arm 10) or PSI-7977 400 mg QD and 800 mg RBV for 12 weeks (Arm 11). HCV GT-1 "null response" subjects receive PSI-7977 400 mg QD, GS-5885, and weight based RBV for 12 weeks (Arm 12). HCV GT-1 treatment naive subjects receive PSI-7977 400 mg QD with weight-based RBV and GS-5885 for 12 weeks (Arm 13); Part 5: HCV GT 1 "null response" subjects receive PSI-7977 400 mg QD with GS-9669 500 mg QD and weight-based RBV for 12 weeks (Arm 14). HCV GT-1 treatment naive subjects receive PSI-7977 400 mg QD with GS-9669 500 mg QD and weight-based RBV for 12 weeks (Arm 15).

Part 6: HCV GT-1 "null response" subjects with fibrosis stage F4 receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 16) or sofosbuvir/GS-5885 FDC with weight-based RBV for 12 weeks (Arm 17). HCV GT-2/3 treatment naive subjects receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 18). HCV GT-2/3 treatment-experienced subjects receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 19). HCV GT-1 hemophiliacs receive sofosbuvir/GS-5885 FDC with weight-based RBV for 12 weeks (Arm 20). HCV GT-1 treatment-naive subjects receive sofosbuvir/GS-5885 FDC with weight-based RBV for 6 weeks (Arm 21). HCV GT-1 treatment-naive subjects receive sofosbuvir/GS-5885 FDC for 6 weeks (Arm 22).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic Genotype 2 or 3 HCV-infection or Genotype 1, serum HCV RNA ≥ 50,000 IU/mL
  • Not co-infected with HIV
  • Use of highly effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

  • History of any other clinically significant chronic liver disease
  • Pregnant or nursing female or male with pregnant female partner
  • History of significant drug allergy to nucleoside/nucleotide analogs.
  • Participation in a clinical study within 3 months prior to first dose
  • Positive result for significant drug use at Screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01260350

Locations
New Zealand
Auckland Clinical Studies Ltd.
Auckland, New Zealand
Christchurch Clinical Studies Trust
Christchurch, New Zealand
Sponsors and Collaborators
Gilead Sciences
Investigators
Principal Investigator: Ed Gane, Assoc. Prof Auckland Clinical Studies Ltd.
  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: NCT01260350     History of Changes
Other Study ID Numbers: P7977-0523, Medsafe
Study First Received: December 13, 2010
Last Updated: January 21, 2014
Health Authority: New Zealand: Medsafe

Keywords provided by Gilead Sciences:
PSI-7977
Sofosbuvir
GS-7977
GS-5885
GS-9669
FDC
ribavirin
RBV
Pegylated Interferon
PEG-IFN
Chronic Hepatitis C Infection
HCV
Hepatitis
Genotype 1
Genotype 2
Genotype 3
GT 1
GT 2
GT 3
Hemophilia

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

ClinicalTrials.gov processed this record on April 16, 2014