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A Phase 2 Dose-Escalation Study of (Albuferon) albumin interferon alfa-2b Combined with Ribavirin in Non-responders to Prior Interferon Based Therapy for Chronic Hepatitis C Infection Phase
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Reported by Jules Levin
EASL, April 26-30, 2006
Vienna, Austria
Author: Vinod Rustgi et. al.
Disclosure: Relationship with Human Genome Sciences, Inc., Rockville, MD - Investigator and Consultant
Study sponsored by Human Genome Sciences, Inc., Rockville, MD, USA
Phase 2 Non Responder Study
Definition of Non-responder to IFN therapy
- Lack of ETR (failed to clear HCV RNA on therapy)
- At least 12 weeks of therapy with lack of EVR
- At least 50% should be PEG-IFN+RBV NR
Author Summary of Safety
1. 48 week safety profile is acceptable for the 900/1200 _g cohorts
- No increase in AE between weeks 12-24-48
- Hematologic reductions stabilize by week 8
- Immunogenicity rates are low and and there are no apparent clinical correlations
- Q4w appears to be better tolerated (less hematologic
reductions)
2. 24+ week safety profile is acceptable for the 1500 _g cohort
3. 12-24 week safety profile for the 1800 _g cohort is comparable to the lower dose cohorts
Conclusions
- Antiviral activity is promising in a non-responder population
- ETR rate is 31% (22/71) in the 900-1200 ug cohorts
- Viral response at w12 follow-up after ETR is 14/71 (20%)
- The 1800 _g arm shows maximal activity at week 24 in GT1 PEG+RBV non-responders
- Long term safety profile is favorable
- No significant increase in severity of adverse events between week 12 and 24
- Hematologic reductions stabilized by week 8 and are well managed with dose reductions
- Little drug accumulation between week 12 and 24
- No significant increase in severity or number of adverse events with increased dose of alb-IFN
Summary of Efficacy
1. Week 48 RNA negativity rate (ETR) was 31% in the 900-1200 _g cohorts
2. The preliminary SVR rate is 20% based on w12 FU. The relapse rate to date is low
3. The 1800 _g cohort shows the greatest w24 HCV RNA negativity rates in GT1, PEG+RBV non responders
4. Few viral breakthroughs were observed. The 1200 _g Q4w cohort is able to maintain RNA negativity
Safety and Tolerability
- Well tolerated with the most common moderate-severe adverse events of fatigue (50%), headache (34%), arthralgia (24%) and myalgia (21%)
- No significant increase in severity over the first 24 weeks
- The incidence was similar across the 5 cohorts
- 10.4% (12/115) required dose reductions for AEs and 5.2% (6/115) required discontinuations for AEs
- 4 serious adverse events: brain aneurysm, abdominal pain (LUQ), ethylene glycol toxicity, appendicitis
Discontinuations
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