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

NCT00277238 | Completed Phase 2 DMC

• 2 other identifiers: B1211002CPG 10101-004
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Hepatitis, Chronic Active

Keywords

HCV; Hepatitis c virus; Virus diseases; Interferon-alpha; Interferons; Liver diseases

Outcome Measures

Primary Outcomes (2)

• Serum HCV RNA concentrations, over 12wks, relative to baseline, early virologic response (EVR)

  12wks

• Serum HCV RNA concentrations, 6months after treatment completed, relative to baseline, sustained virologic response (SVR)

  72wks

Secondary Outcomes (5)

• Safety and Tolerability: adverse events, vital signs, clinical and laboratory parameters, depression score, physical exam, electrocardiogram (ECG), ophthalmologic exam (if required)

  28wks

• Dose exposure

  24wks

• Child-Pugh score

  24wks

• Serum Biomarkers: cytokines and chemokines, over time, relative to baseline

  24wks

• Immunophenotyping profile, over time, relative to baseline, HCV specific immune response, over time, relative to baseline, level of innate immune activation at baseline

  24wks

Study Arms (4)

CPG10101 (0.2) + pegylated inteferon + ribavirin

EXPERIMENTAL

Drug: CPG10101

CPG10101 (0.5) + pegylated inteferon + ribavirin

EXPERIMENTAL

Drug: CPG10101

Pegylated interferon + ribavirin

ACTIVE COMPARATOR

Drug: Control

CPG10101 + pegylated interferon + ribavirin (rollover)

EXPERIMENTAL

Drug: CPG10101

Interventions

CPG10101 DRUG

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

CPG10101 (0.2) + pegylated inteferon + ribavirin

Control DRUG

Pegylated interferon alfa-2b, subcutaneous, 1.5 ug/kg, weekly, 12wks Ribavirin, oral, 800-1400mg/day (weight-based), daily, 12wks

Pegylated interferon + ribavirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (14)

Pfizer Investigational Site

Chicago, Illinois, 60611, United States

Location

Pfizer Investigational Site

Indianapolis, Indiana, 46202, United States

Location

Pfizer Investigational Site

New Orleans, Louisiana, 70115, United States

Location

Pfizer Investigational Site

Detroit, Michigan, 48202-2689, United States

Location

Pfizer Investigational Site

Kansas City, Missouri, 64131, United States

Location

Pfizer Investigational Site

St Louis, Missouri, 63104, United States

Location

Pfizer Investigational Site

New York, New York, 10021, United States

Location

Pfizer Investigational Site

Durham, North Carolina, 27710, United States

Location

Pfizer Investigational Site

Cleveland, Ohio, 44195, United States

Location

Pfizer Investigational Site

Hershey, Pennsylvania, 17033, United States

Location

Pfizer Investigational Site

Germantown, Tennessee, 38138, United States

Location

Pfizer Investigational Site

Dallas, Texas, 75208, United States

Location

Pfizer Investigational Site

San Antonio, Texas, 78215, United States

Location

Pfizer Investigational Site

Richmond, Virginia, 23249, United States

Location

MeSH Terms

Conditions

Hepatitis, Chronic; Hepatitis C; Virus Diseases; Liver Diseases

Condition Hierarchy (Ancestors)

Hepatitis; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Flaviviridae Infections; RNA Virus Infections

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 13, 2006
• First Posted: January 16, 2006
• Study Start: February 1, 2006
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: March 8, 2017

Record last verified: 2017-03

Locations

US (14)