Clinical trial NCT01260350: Open-Labeled Study of PSI-7977 and RBV With and Without PEG-IFN in Treatment-Naïve Patients With HCV GT2 or GT3
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C Infection
Keywords: 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
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-12-15
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Part 1: HCV genotype 2 or 3: participants will receive SOF 400 mg once daily with weight-based RBV for 12 weeks. Participants will be randomized in equal proportions to: no PEG (Arm 1), PEG for 4 weeks (Arm 2), PEG for 8 weeks (Arm 3), or PEG for 12 weeks (Arm 4).

Part 2: HCV genotype 2 or 3: participants will receive SOF 400 mg once daily (monotherapy) for 12 weeks (Arm 5), or SOF 400 mg once daily with PEG and weight-based RBV for 8 weeks (Arm 6); HCV genotype 1: null responders (did not respond to their prior treatment) will receive SOF 400 mg once daily with weight-based RBV for 12 weeks (Arm 7).

Part 3: HCV genotype 1 treatment-naive (Arm 8) or HCV genotype 2 or 3 treatment-experienced participants (Arm 9) will receive SOF 400 mg once daily in combination with weight-based RBV for 12 weeks.

Part 4: HCV genotype 2 or 3 treatment naive participants will receive SOF 400 mg once daily with weight-based RBV for 8 weeks (Arm 10) or SOF 400 mg once daily and 800 mg RBV for 12 weeks (Arm 11). HCV genotype 1 null responders will receive SOF 400 mg once daily, ledipasvir (LDV), and weight based RBV for 12 weeks (Arm 12). HCV genotype-1 treatment naive participants will receive SOF 400 mg once daily with weight-based RBV and LDV for 12 weeks (Arm 13).

Part 5: HCV genotype 1 null responders will receive SOF 400 mg once daily with GS-9669 500 mg once daily and weight-based RBV for 12 weeks (Arm 14). HCV genotype-1 treatment naive participants receive SOF 400 mg once daily with GS-9669 500 mg once daily and weight-based RBV for 12 weeks (Arm 15).

Part 6: HCV genotype 1 null responders with Stage F4 fibrosis will receive LDV/SOF FDC for 12 weeks (Arm 16) or LDV/SOF FDC with weight-based RBV for 12 weeks (Arm 17). HCV genotype 2 or 3 treatment-naive participants will receive LDV/SOF FDC for 12 weeks (Arm 18). HCV genotype 2 or 3 treatment-experienced participants will receive LDV/SOF FDC for 12 weeks (Arm 19). HCV genotype 1 hemophiliacs will receive LDV/SOF FDC with weight-based RBV for 12 weeks (Arm 20). HCV genotype 1 treatment-naive participants will receive LDV/SOF FDC with weight-based RBV for 6 weeks (Arm 21). HCV genotype 1 treatment-naive participants will receive LDV/SOF FDC for 6 weeks (Arm 22).

Eligibility 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

Primary outcomes:
measure: Percentage of Participants Who Experienced Adverse Events
timeFrame: Up to 12 weeks plus 30 days
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)
timeFrame: Posttreatment Week 12
measure: Percentage of Participants With HCV RNA < LOD at Week 6
timeFrame: Week 6
measure: Percentage of Participants With HCV RNA < LOD at Week 8
timeFrame: Week 8
measure: Percentage of Participants With HCV RNA < LOD at Week 12
timeFrame: Week 12
measure: Change From Baseline in HCV RNA at Week 6
timeFrame: Baseline to Week 6
measure: Change From Baseline in HCV RNA at Week 8
timeFrame: Baseline to Week 8
measure: Change From Baseline in HCV RNA at Week 12
timeFrame: Baseline to Week 12
measure: Percentage of Participants With Virologic Failure
timeFrame: Up to Posttreatment Week 24
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies Ltd.
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust
Study officials:
affiliation: Gilead Sciences
name: Robert H. Hyland, DPhil
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.