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

Chronic Hepatitis C Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01260350
• Other study ID #: P7977-0523
• Secondary ID: Medsafe
• Status: Completed
• Phase: Phase 2
• First received: December 13, 2010
• Last updated: November 7, 2014
• Start date: December 2010
• Est. completion date: December 2013

Study information

• Verified date: November 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: New Zealand: Medsafe
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 292
• Est. completion date: December 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C Infection
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Infection

Intervention

Drug:
• SOF
Sofosbuvir (SOF) tablets administered orally once daily
• RBV
Ribavirin (RBV) capsules administered orally in a divided daily dose
• PEG
Peginterferon alfa-2a (PEG) administered via subcutaneous injection once weekly
• LDV
Ledipasvir (LDV) tablets administered orally once daily
• GS-9669
GS-9669 tablets administered orally once daily
• LDV/SOF
LDV/SOF fixed-dose combination (FDC) tablet administered once daily

Locations

Country	Name	City	State
New Zealand	Auckland Clinical Studies Ltd.	Auckland
New Zealand	Christchurch Clinical Studies Trust	Christchurch

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

New Zealand, 

References & Publications (2)

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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Experienced Adverse Events	Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.	Up to 12 weeks plus 30 days	No
Secondary	Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)	SVR12 was defined as HCV RNA < the limit of detection (LOD; < 15 IU/mL) 12 weeks after the last dose of study drug.	Posttreatment Week 12	No
Secondary	Percentage of Participants With HCV RNA < LOD at Week 6		Week 6	No
Secondary	Percentage of Participants With HCV RNA < LOD at Week 8	Data are not presented for Group 21 which ended treatment after Week 6.	Week 8	No
Secondary	Percentage of Participants With HCV RNA < LOD at Week 12	Data are not presented for Groups 6, 10, and 21 which ended treatment after Week 8 or Week 6.	Week 12	No
Secondary	Change From Baseline in HCV RNA at Week 6		Baseline to Week 6	No
Secondary	Change From Baseline in HCV RNA at Week 8	Data are not presented for Group 21 which ended treatment after Week 6.	Baseline to Week 8	No
Secondary	Change From Baseline in HCV RNA at Week 12	Data are not presented for Groups 6, 10, and 21 which ended treatment after Week 8 or Week 6. Data are not presented for Groups 16, 17, 18, and 20 because participants with detectable HCV RNA discontinued due to protocol-specified stopping rules.	Baseline to Week 12	No
Secondary	Percentage of Participants With Virologic Failure	The percentage of participants with on-treatment virologic failure (viral breakthrough, rebound, or nonresponse) or following treatment (viral relapse) was summarized.; On-treatment virologic failure was defined as: Viral breakthrough (confirmed HCV RNA = LOD after having previously had HCV RNA < LOD while on treatment),; Viral rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, or; Nonresponse (HCV RNA persistently = LOD through 6 weeks of treatment); Viral relapse was defined as confirmed HCV RNA = LOD during the posttreatment period having achieved HCV RNA < LOD at the last on-treatment visit.	Up to Posttreatment Week 24	No