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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01260350




Registration number
NCT01260350
Ethics application status
Date submitted
13/12/2010
Date registered
15/12/2010
Date last updated
17/11/2014

Titles & IDs
Public title
Open-Labeled Study of PSI-7977 and RBV With and Without PEG-IFN in Treatment-Naïve Patients With HCV GT2 or GT3
Scientific 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
Secondary ID [1] 0 0
Medsafe
Secondary ID [2] 0 0
P7977-0523
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis C Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SOF
Treatment: Drugs - RBV
Treatment: Drugs - PEG
Treatment: Drugs - LDV
Treatment: Drugs - GS-9669
Treatment: Drugs - LDV/SOF

Experimental: Group 1: SOF+RBV 12 wk: GT 2 or 3, TN - Treatment-naive (TN) participants with genotype (GT) 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.

Experimental: Group 2: SOF+RBV 12 wk+PEG 4 wk: GT 2 or 3, TN - Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 4 weeks.

Experimental: Group 3: SOF+RBV 12 wk+PEG 8 wk: GT 2 or 3, TN - Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks plus PEG 180 µg once weekly for 8 weeks.

Experimental: Group 4: SOF+RBV+PEG 12 wk: GT 2 or 3, TN - Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily+weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 12 weeks.

Experimental: Group 5: SOF 12 wk: GT 2 or 3, TN - Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily for 12 weeks.

Experimental: Group 6: SOF+RBV+PEG 8 wk: GT 2 or 3, TN - Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus PEG 180 µg once weekly for 8 weeks.

Experimental: Group 7: SOF+RBV 12 wk: GT 1, TE - Treatment-experienced (TE) participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.

Experimental: Group 8: SOF+RBV 12 wk: GT 1, TN - Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.

Experimental: Group 9: SOF+RBV 12 wk: GT 2 or 3, TE - Treatment-experienced participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.

Experimental: Group 10: SOF+RBV 8 wk: GT 2 or 3, TN - Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 8 weeks.

Experimental: Group 11: SOF+RBV 12 wk: GT 2 or 3, TN - Treatment-naive participants with genotype 2 or 3 HCV infection will receive SOF 400 mg once daily plus split-dose RBV (800 mg in a divided daily dose) for 12 weeks.

Experimental: Group 12: SOF+RBV+LDV 12 wk: GT 1, TE - Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.

Experimental: Group 13: SOF+RBV+LDV 12 wk: GT 1, TN - Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus LDV 90 mg once daily for 12 weeks.

Experimental: Group 14: SOF+RBV+GS-9669 12 wk: GT 1, TE - Treatment-experienced participants with genotype 1 HCV infection who did not respond to prior treatment will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.

Experimental: Group 15: SOF+RBV+GS-9669 12 wk: GT 1, TN - Treatment-naive participants with genotype 1 HCV infection will receive SOF 400 mg once daily plus weight-based RBV (1000-1200 in a divided daily dose) plus GS-9669 500 mg once daily for 12 weeks.

Experimental: Group 16: LDV/SOF FDC 12 wk: GT 1, fibrosis - Treatment-experienced participants with genotype 1 HCV infection and Stage F4 fibrosis who did not respond to prior treatment will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.

Experimental: Group 17: LDV/SOF FDC+RBV 12 wk: GT 1, fibrosis - Treatment-experienced participants with genotype 1 HCV infection with Stage F4 fibrosis who did not respond to prior treatment will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.

Experimental: Group 18: LDV/SOF FDC 12 wk: GT 2 or 3, TN - Treatment-naive participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.

Experimental: Group 19: LDV/SOF FDC 12 wk: GT 2 or 3, TE - Treatment-experienced participants with genotype 2 or 3 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily for 12 weeks.

Experimental: Group 20: LDV/SOF FDC+RBV 12 wk: GT 1, hemophiliac - Hemophiliac participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 12 weeks.

Experimental: Group 21: LDV/SOF FDC+RBV 6 wk: GT 1, TN - Treatment-naive participants with genotype 1 HCV infection will receive LDV 90 mg/SOF 400 mg FDC once daily plus weight-based RBV (1000-1200 in a divided daily dose) for 6 weeks.

Experimental: Group 22: LDV/SOF FDC 6 wk: GT 1, TN - Treatment-naive participants with genotype 1 HCV infection were randomized to receive LDV 90 mg/SOF 400 mg FDC once daily for 6 weeks.


Treatment: Drugs: SOF
Sofosbuvir (SOF) tablets administered orally once daily

Treatment: Drugs: RBV
Ribavirin (RBV) capsules administered orally in a divided daily dose

Treatment: Drugs: PEG
Peginterferon alfa-2a (PEG) administered via subcutaneous injection once weekly

Treatment: Drugs: LDV
Ledipasvir (LDV) tablets administered orally once daily

Treatment: Drugs: GS-9669
GS-9669 tablets administered orally once daily

Treatment: Drugs: LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Experienced Adverse Events
Timepoint [1] 0 0
Up to 12 weeks plus 30 days
Secondary outcome [1] 0 0
Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)
Timepoint [1] 0 0
Posttreatment Week 12
Secondary outcome [2] 0 0
Percentage of Participants With HCV RNA < LOD at Week 6
Timepoint [2] 0 0
Week 6
Secondary outcome [3] 0 0
Percentage of Participants With HCV RNA < LOD at Week 8
Timepoint [3] 0 0
Week 8
Secondary outcome [4] 0 0
Percentage of Participants With HCV RNA < LOD at Week 12
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Change From Baseline in HCV RNA at Week 6
Timepoint [5] 0 0
Baseline to Week 6
Secondary outcome [6] 0 0
Change From Baseline in HCV RNA at Week 8
Timepoint [6] 0 0
Baseline to Week 8
Secondary outcome [7] 0 0
Change From Baseline in HCV RNA at Week 12
Timepoint [7] 0 0
Baseline to Week 12
Secondary outcome [8] 0 0
Percentage of Participants With Virologic Failure
Timepoint [8] 0 0
Up to Posttreatment Week 24

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2013
Sample size
Target
Accrual to date
Final
292
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is to assess the safety and tolerability of sofosbuvir (SOF) 400 mg with and without ribavirin (RBV) and/or with and without pegylated interferon alfa-2a (PEG) in subjects with genotype 1, 2 or 3 hepatitis C (HCV) infection.
Trial website
https://clinicaltrials.gov/study/NCT01260350
Trial related presentations / publications
Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Subramanian GM, Symonds WT, McHutchison JG, Pang PS. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology. 2014 Mar;146(3):736-743.e1. doi: 10.1053/j.gastro.2013.11.007. Epub 2013 Nov 18.
Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, Hindes RG, Berrey MM. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34-44. doi: 10.1056/NEJMoa1208953.
Public notes

Contacts
Principal investigator
Name 0 0
Robert H. Hyland, DPhil
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01260350