CPG10101 Combination Therapy For The Treatment Of Hepatitis C In Non-Responder (Null And Partial Responder) Hepatitis C Virus (HCV) Genotype 1 Infected Subjects

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00277238
First received: January 13, 2006
Last updated: April 21, 2011
Last verified: April 2011
  Purpose

The purpose of this study is to determine the efficacy and tolerability of CPG 10101 at two different dose levels with pegylated-interferon-alpha 2B (PEG-IFN) plus ribavirin (RBV) compared to PEG-IFN and RBV without CPG 10101 in HCV positive subjects who were classified as non-responders to previous adequate PEG-IFN plus RBV therapy.


Condition Intervention Phase
Hepatitis, Chronic Active
Drug: CPG10101
Drug: Control
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CPG 10101 Combination Therapy for the Treatment of Hepatitis C: A Phase II Randomized, Open Label, Multi-Center, Parallel Arm, Controlled Trial of CPG 10101 at Two Different Dose Levels With Pegylated-Interferon-Alpha 2B (PEG-IFN) Plus Ribavirin (RBV) or PEG-IFN Plus RBV Without CPG 10101 in the Treatment of Non-Responder (Null and Partial Responder) HCV Genotype 1 Infected Subjects

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Serum HCV RNA concentrations, over 12wks, relative to baseline, early virologic response (EVR) [ Time Frame: 12wks ] [ Designated as safety issue: No ]
  • Serum HCV RNA concentrations, 6months after treatment completed, relative to baseline, sustained virologic response (SVR) [ Time Frame: 72wks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and Tolerability: adverse events, vital signs, clinical and laboratory parameters, depression score, physical exam, electrocardiogram (ECG), ophthalmologic exam (if required) [ Time Frame: 28wks ] [ Designated as safety issue: Yes ]
  • Dose exposure [ Time Frame: 24wks ] [ Designated as safety issue: No ]
  • Child-Pugh score [ Time Frame: 24wks ] [ Designated as safety issue: No ]
  • Serum Biomarkers: cytokines and chemokines, over time, relative to baseline [ Time Frame: 24wks ] [ Designated as safety issue: No ]
  • Immunophenotyping profile, over time, relative to baseline, HCV specific immune response, over time, relative to baseline, level of innate immune activation at baseline [ Time Frame: 24wks ] [ Designated as safety issue: No ]

Enrollment: 113
Study Start Date: February 2006
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CPG10101 (0.2) + pegylated inteferon + ribavirin Drug: CPG10101
CPG10101, subcutaneous, 0.2mg/kg, weekly, 24wks Pegylated interferon alfa-2b, subcutaneous, 1.5ug/kg, weekly, 24wks Ribavirin, oral, 800-1400mg/day (weight-based), daily, 24wks
Experimental: CPG10101 (0.5) + pegylated inteferon + ribavirin Drug: CPG10101
CPG10101, subcutaneous, 0.5mg/kg, weekly, 24wks Pegylated interferon alfa-2b, subcutaneous, 1.5 ug/kg, weekly, 24wks Ribavirin, oral, 800-1400mg/day (weight-based), daily, 24wks
Active Comparator: Pegylated interferon + ribavirin Drug: Control
Pegylated interferon alfa-2b, subcutaneous, 1.5 ug/kg, weekly, 12wks Ribavirin, oral, 800-1400mg/day (weight-based), daily, 12wks
Experimental: CPG10101 + pegylated interferon + ribavirin (rollover) Drug: CPG10101
CPG10101, subcutaneous, 0.5mg/kg, weekly, 24wks Pegylated interferon alfa-2b, subcutaneous, 1.5 ug/kg, weekly, 24wks Ribavirin, oral, 800-1400mg/day (weight-based), daily, 24wks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

HCV positive subjects documented by serum HCV RNA concentration > 100,000 IU/mL within 21 days of first study treatment Receipt of adequate previous PEG-IFN and RBV therapy for a minimum of 12 weeks (PEG-IFN alpha-2a doses of > 180 μg/wk or PEG-IFN alpha-2b 1.5 µg/kg/wk and at least 800 mg RBV daily) not resulting in a minimum of a 2 log decrease in HCV RNA concentrations while on treatment (null responders). Or, receipt of adequate previous treatment PEG-IFN and RBV therapy for a minimum of 24 weeks (PEG-IFN alpha-2a doses of ≥ 180 μg/wk or PEG-IFN alpha-2b 1.5 µg/kg/wk and at least 800 mg RBV daily) resulting in a minimum of a 2 log decrease in serum HCV RNA concentrations by 12 weeks of treatment but not resulting in an undetectable viral load after 24 weeks of treatment (partial responders). If dose modifications were necessary during the treatment due to adverse events, the subject must have received at least 80% of the PEG-IFN dose and 80% of the RBV dose to be eligible for the study.

HCV genotype 1 only; other HCV genotypes are excluded. Adults, 18+ years old Written informed consent Liver biopsy within 5 years of the first dose of study drug, documenting changes consistent with hepatitis C

Adequate bone marrow, liver, and renal function demonstrated by:

  • Hemoglobin > 12 g/dL for females and > 13 g/dL for males
  • White blood cell (WBC) > 3,000/mm3
  • Neutrophils > 1,500/mm3
  • Platelets > 80,000/mm3
  • Total bilirubin < 1.6 mg/dL
  • Direct bilirubin < 1.5 upper limit of normal. If indirect bilirubin is elevated, Gilbert's disease must be documented in chart and substantiated.
  • Albumin > 3.7 g/dL and < 4.9 g/dL
  • Serum creatinine < upper limit of normal per central laboratory. If serum creatinine is > upper limit of normal then calculated creatinine clearance has to be > 100 mL/min (by Cockcroft-Gault formula) for patient to be eligible.

Negative pregnancy test in women of childbearing potential. Females of childbearing potential and males who have partners of childbearing potential must use two forms of effective contraception during treatment and during the 6 months after treatment has been concluded.

Serum thyroid stimulating hormone (TSH) levels within normal ranges within 21 days of first study treatment, regardless of treatment with L-thyroxin.

Exclusion Criteria:

Treatment with any IFN based therapies and/or antiviral therapies within 30 days of the first dose of study drug Subjects who have previously received an HCV vaccine Child-Pugh Class B or C History of psychiatric conditions including, but not limited to, psychosis, suicidal ideations, or major depression. Subjects with mild to moderate depression in the past who have a normal to mild Beck Depression Inventory score and no prior history of suicidal gestures or attempts may be enrolled if, in the Investigator's opinion, they are suitable for treatment.

Significant cardiovascular disease (e.g., New York Heart Association [NYHA] class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; or uncontrolled atrial or ventricular cardiac arrhythmias) History of immunodeficiency or autoimmune disease including autoimmune hepatitis, allogeneic transplant, or pre-existing autoimmune or antibody-mediated disease including, but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia.

Other serious medical conditions including, but not limited to:

  • HIV-1
  • Hepatitis B (positive hepatitis B surface antigen [HBsAg])
  • Cancer (active tumors in the last 5 years)
  • Pregnant, partners of pregnant women, or nursing women
  • Alcohol or drug misuse within 90 days of screening Use of immunosuppressive doses of steroids or any anti-metabolite therapies within 3 months of entry into the study (inhaled and topical corticosteroids are permitted).

Receipt of any vaccine or immunoglobulin within 30 days before the first dose of study drug. Flu vaccines are only allowed once the subjects are qualified for 36 additional weeks of treatment.

Prior administration of oligodeoxynucleotides (including study medication CPG 10101), ribozymes, or any known allergy to CPG 10101, interferon, RVN or their excipients.

Receipt of any investigational drug therapy within 30 days before the first dose of study drug.

Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00277238

Locations
United States, Illinois
Pfizer Investigational Site
Chicago, Illinois, United States, 60611
United States, Indiana
Pfizer Investigational Site
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Pfizer Investigational Site
New Orleans, Louisiana, United States, 70115
United States, Michigan
Pfizer Investigational Site
Detroit, Michigan, United States, 48202-2689
United States, Missouri
Pfizer Investigational Site
Kansas City, Missouri, United States, 64131
Pfizer Investigational Site
St. Louis, Missouri, United States, 63104
United States, New York
Pfizer Investigational Site
New York, New York, United States, 10021
United States, North Carolina
Pfizer Investigational Site
Durham, North Carolina, United States, 27710
United States, Ohio
Pfizer Investigational Site
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Pfizer Investigational Site
Hershey, Pennsylvania, United States, 17033
United States, Tennessee
Pfizer Investigational Site
Germantown, Tennessee, United States, 38138
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75208
Pfizer Investigational Site
San Antonio, Texas, United States, 78215
United States, Virginia
Pfizer Investigational Site
Richmond, Virginia, United States, 23249
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00277238     History of Changes
Other Study ID Numbers: B1211002, CPG 10101-004
Study First Received: January 13, 2006
Last Updated: April 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
HCV
Hepatitis c virus
Virus diseases
Interferon-alpha
Interferons
Liver diseases

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferon-alpha
Interferons
Peginterferon alfa-2b
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 05, 2015