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Early Viral Response to New HCV Drug CPG 10101 Toll-Receptor Antagonist,
in Combination with Pegylated Interferon and/or Ribavirin, in Chronic HCV Genotype 1 Infected Patients with Prior Relapse Response
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J.G. McHutchison1, R. Ghalib1, E. Lawitz1, P. Kwo1, B. Freilich1, A. Muir1
F. Masciari2, M.L. Morris2, J.L. Himes2, M. Al-Adhami2, B.R. Bacon1
1CPG 10101-003 Study Group
2Coley Pharmaceutical Group, Inc.
Reported by Jules
EASL, April 2006, Vienna, Austria
CPG 10101 Combination Therapy
in Treatment-Refractory (Relapsed) HCV Patients
Author Summary & Conclusions
- CPG 10101 improves early antiviral activity of PEG-IFN + RBV in Treatment-Refractory patients (RRs)
- Greater RVR, EVR, & HCV RNA Undetectable responses in CPG + PEG-IFN + RBV group than PEG-IFN + RBV group
- CPG 10101 appears synergistic with PEG-IFN + RBV
- CPG 10101 generally well tolerated in combinations with PEG-IFN and/or RBV
- EVR patients continuing treatment 48 weeks
Safety & efficacy (SVR) forthcoming
Additional Ongoing CPG 10101 Study
- Randomized, controlled Phase 2 study in genotype 1 Treatment-Refractory NRs
- 90 patients (1:1:1)
1. 0.2 mg/kg CPG 10101 + PEG-IFN + RBV
2. 0.5 mg/kg CPG 10101 + PEG-IFN + RBV
3. PEG-IFN + RBV
- Currently enrolling
- Interim 12 weeks results by end of 2006
Future international trials planned in Treatment-Refractory patients.
CPG 10101 (ACTILON ):
Investigational TLR9 Agonist for Treatment of HCV
CPG 10101 stimulates an immune response:
- Synthetic Oligodeoxy-nucleotide (ODN)
- Targeted Mechanism
- TLR9 agonist
- DC-mediated immune stimulation
- Immunological Mechanism
- pDC-mediated
- Innate
- Adaptive
Synergistic with IFN-_
Study Objectives
- Safety & tolerability
- Plasma viral RNA levels
(RVR, EVR, OTR, ETR, SVR)
Study Design
- Multicenter, randomized Phase Ib
- Genotype 1, PEG-IFN + RBV Treatment-Refractory (RRs)
- Interim 12 week results presented
- 12 week treatment 48 week if ≥2 log10 reduction at Week 12
- HCV RNA Undetectable at Week 48 SVR
Study Population & Demographics
There were 14-16 patients in each study arm. Average age: 48-50 yrs. Weight: 87-92 kg. Gender 44-60% female except 0% in CPG10101 arm. Mostly Caucasian, 1 Black, 9 Hispanics. HCV RNA: - to 6.4 log IU/mL. Baseline HCV RNA >800,000 Iu/mL: 67-93%.
Safety & Tolerability
- CPG 10101 combinations generally well tolerated
- AEs were transient & consistent with mechanism
- Predominantly mild/moderate in intensity in all groups
- Most frequent: Pyrexia, fatigue, headache, nausea
- CPG 10101 only added mild AEs
- Predominantly injection site reactions
- 6 withdrawals
- 2 Drug-related AE
- Injection site cellulitis & necrosis (CPG 10101 + PEG-IFN) (SAE)
- Rash (CPG 10101)
- 2 Consent
- 1 Non-compliance & 1 lost to follow up
- 1 Additional CPG 10101-related SAE at Week 12
Immediate hypersensitivity (CPG 10101 + PEG-IFN)
- No evidence of ALT flares
Intensity of Adverse Events
AEs of moderate & severe intensity were comparable across all groups.
Green=grade1
Yellow=grade2
Orange=grade3
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