Efficacy and Safety of Adding Alisporivir (DEB025) to Peginterferon (IFN) Alfa-2a (Peg-IFN Alfa-2a) and Ribavirin in Chronic HCV Genotype 1 Patients Who Relapsed or Did Not Respond to Previous Treatment

• Alisporivir (Drug), also known as DEB025, ALV: ALV 200 mg soft gel capsules administered orally
• Peginterferon alfa-2a (Drug), also known as Pegasys®, PEG: PEG 180 μg administered via subcutaneous (s.c.) injection once weekly
• Ribavirin (Drug), also known as Copegus®, RBV: RBV 200 mg tablets (weight-based dose: < 75 mg = 1000 mg/day; ≥ 75 kg = 1200 mg/day) administered orally in a divided daily dose
• Placebo (Drug), also known as ALV Placebo: ALV placebo soft gel capsules administered orally

Primary outcomes

• Percentage of Participants With Complete Early Viral Response Below the Limit of Quantification (cEVR-LOQ) [after 12 weeks of treatment]: cEVR-LOQ was defined as serum HCV RNA below the limit of quantification (< LOQ; i.e., 25 IU/mL) after 12 weeks of treatment. Post-switch groups were assessed 12 weeks after the switch.

Secondary outcomes

• Percentage of Participants With Complete Early Viral Response Below the Limit of Detection (cEVR-LOD) [after 12 weeks of treatment]: cEVR-LOD was defined as serum HCV RNA below the limit of detection (< LOD; i.e., 10 IU/mL) after 12 weeks of treatment. Post-switch groups were assessed 12 weeks after the switch.
• Percentage of Participants Who Achieved Sustained Viral Response 12 Weeks After Treatment (SVR12)-LOQ and SVR12-LOD [12 weeks after treatment]: SVR12-LOQ and SVR12-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD 12 weeks after treatment, respectively.
• Percentage of Participants Who Achieved Sustained Viral Response 24 Weeks After Treatment (SVR24)-LOQ and SVR24-LOD [24 weeks after treatment]: SVR24-LOQ and SVR24-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD 24 weeks after treatment, respectively.
• Percentage of Participants With Rapid Viral Response (RVR)-LOQ and RVR-LOD [after 4 weeks of treatment]: RVR-LOQ and RVR-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD after 4 weeks of treatment, respectively. Post-switch groups were assessed 4 weeks after the switch.
• Percentage of Participants With Partial Early Virologic Response After 12 Weeks of Treatment (pEVR)-LOQ and pEVR-LOD [after 12 weeks of treatment]: pEVR-LOQ and pEVR-LOD were defined as a ≥ 2 log10 decrease in HCV RNA and still detectable (≥ LOQ and ≥ LOD, respectively) after 12 weeks of treatment. Post-switch groups were assessed 12 weeks after the switch.
• Percentage of Participants With End of Treatment Response (ETR)-LOQ and ETR-LOD [within 48 weeks]: ETR-LOQ and ETR-LOD were defined as serum HCV RNA < LOQ and serum HCV RNA < LOD at treatment end (completed or prematurely discontinued), respectively.
• Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End [Up to 48 weeks]
• Percentage of Participants With On-treatment Viral Breakthrough [within 48 weeks]: On-treatment viral breakthrough was defined as either: * Confirmed increase of HCV RNA ≥1 log10 above nadir (nadir = lowest HCV RNA value during treatment), or * HCV RNA becoming ≥ 100 IU/mL after previously being undetectable (< LOQ) during treatment
• Percentage of Participants With Viral Relapse [within 24 weeks after treatment]: Viral relapse was defined as reappearance of detectable HCV RNA after previously being undetectable (< LOQ) during treatment.

Sex: All, ages: 18 Years to 70 Years

Inclusion criteria:

* Chronic HCV genotype 1 viral infection
* HCV RNA ≥ 1,000 IU/ml assessed by quantitative polymerase chain reaction (qPCR) or equivalent at screening
* Previous non-responders/relapsers to PEG and RBV after treatment for at least 12 weeks

Exclusion criteria:

* Treatment with any anti-HCV drug (whether approved or investigational) within 3 months prior to screening
* Women of child-bearing potential unless using highly effective
* Any other cause of relevant liver disease other than HCV
* Other protocol-defined inclusion/exclusion criteria may apply

Participant flow

Outcome results

• Percentage of Participants With Complete Early Viral Response Below the Limit of Quantification (cEVR-LOQ) (Primary), Number, percentage of participants: Treatment A 48.2; Treatment B 61.1; Treatment C 35.5; Treatment D 74.3; Treatment C1A 45.5; Treatment C2A 80.0
• Percentage of Participants With Complete Early Viral Response Below the Limit of Detection (cEVR-LOD) (Secondary), Number, percentage of participants: Treatment A 39.1; Treatment B 41.7; Treatment C 20.9; Treatment D 58.7; Treatment C1A 39.4; Treatment C2A 73.3
• Percentage of Participants Who Achieved Sustained Viral Response 12 Weeks After Treatment (SVR12)-LOQ and SVR12-LOD (Secondary), Number, percentage of participants: Treatment A 42.7; Treatment B 51.9; Treatment C 14.5; Treatment D 65.1; Treatment C1A 18.2; Treatment C2A 53.3
• Percentage of Participants Who Achieved Sustained Viral Response 24 Weeks After Treatment (SVR24)-LOQ and SVR24-LOD (Secondary), Number, percentage of participants: Treatment A 41.8; Treatment B 51.9; Treatment C 14.5; Treatment D 65.1; Treatment C1A 18.2; Treatment C2A 53.3
• Percentage of Participants With Rapid Viral Response (RVR)-LOQ and RVR-LOD (Secondary), Number, percentage of participants: Treatment A 20.9; Treatment B 25.0; Treatment C 7.3; Treatment D 41.3; Treatment C1A 39.4; Treatment C2A 56.7
• Percentage of Participants With Partial Early Virologic Response After 12 Weeks of Treatment (pEVR)-LOQ and pEVR-LOD (Secondary), Number, percentage of participants: Treatment A 38.2; Treatment B 28.7; Treatment C 31.8; Treatment D 11.9; Treatment C1A 3.0; Treatment C2A 6.7
• Percentage of Participants With End of Treatment Response (ETR)-LOQ and ETR-LOD (Secondary), Number, percentage of participants: Treatment A 68.2; Treatment B 74.1; Treatment C 33.6; Treatment D 82.6; Treatment C1A 51.5; Treatment C2A 73.3
• Percentage of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Had Normalized ALT at Treatment End and Study End (Secondary), Number, percentage of participants: Treatment A 77.4; Treatment B 77.6; Treatment C 59.0; Treatment D 83.0; Treatment C1A 35.7; Treatment C2A 28.6
• Percentage of Participants With On-treatment Viral Breakthrough (Secondary), Number, percentage of participants: Treatment A 12.7; Treatment B 9.3; Treatment C 5.5; Treatment D 2.8; Treatment C1A 6.1; Treatment C2A 10.0
• Percentage of Participants With Viral Relapse (Secondary), Number, percentage of participants: Treatment A 19.1; Treatment B 18.5; Treatment C 17.3; Treatment D 12.8; Treatment C1A 30.3; Treatment C2A 13.3

Adverse events

Serious adverse events by term

5 more terms not shown.

Other adverse events by term

26 more terms not shown.

Limitations and caveats: In April 2012, ALV and placebo were discontinued in all participants. Participants remained on PEG and RBV treatment.

• Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals