E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is a Phase 2, randomized, double-blind, comparator-controlled study of IMO-2125 in hepatitis C-infected patients who were previously nonresponders to standard treatment (pegylated-interferon plus ribavirin) – that is, were treated at least 12 weeks and never achieved an undetectable viral load during or at the end of treatment. The population under study is nonresponder patients with chronic hepatitis C virus (HCV) infection. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of different regimens of IMO-2125 in combination with ribavirin compared to PegasysTM plus ribavirin administered for 12 weeks to patients with chronic HCV infection who were nonresponders to prior treatment with pegylated-interferon plus ribavirin. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of 12-week treatment with IMO-2125 plus ribavirin on viral load in patients with chronic HCV infection who were nonresponders to prior treatment with peg-IFN plus ribavirin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To qualify for enrollment, a patient must meet all of the following criteria: - Has HCV plasma viral load >10,000 IU/mL; - Is infected only with HCV genotype 1; - Has previously received at least 12 weeks of treatment with pegylated-interferon plus ribavirin and failed to achieve an undetectable viral load at any time during or at the end of treatment; - Has not previously received more than four (4) weeks of an investigational treatment for HCV and must not have received any such treatment in the past three (3) months; - Has no other cause of significant liver disease, including, but not limited to, hepatitis B, drug- or alcohol related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis, or primary biliary cirrhosis. - Has adequate liver function as documented by: – alanine aminotransferase (ALT) value <10x the upper limit of normal (ULN) – total bilirubin <1.5x ULN; – albumin >3.0 g/dL – international normalized ratio (INR) <1.5; - Has documented absence of liver cirrhosis either by liver biopsy within the past 36 months or by FibroScanTM within the past 18 months; - Has documented absence of a liver mass consistent with malignancy by an imaging study (i.e., ultrasound, radionucleotide liver scan, abdominal CT or MRI scan) within the past 6 months; - Is age 18 to 65 years, inclusive; - Completes the informed consent procedure (see Section 15.3), including signing and dating the informed consent form; - Female subjects must have a negative pregnancy test at screening and on Day 1 prior to start of treatment; - Female subjects of childbearing potential (see Section 8.3.1) and male subjects who have partners of childbearing potential must agree to use effective birth control (contraception) from Screening through the treatment period and for six (6) months after the last dose of ribavirin. |
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E.4 | Principal exclusion criteria |
- Has known hypersensitivity to any oligodeoxynucleotide; - Is nursing; - Has body weight <50 kg; - Has BMI >34.9 kg/m2; - Regularly consumes >3 drinks of alcoholic beverages (beer, wine, or distilled spirits) per day; - Has used any cocaine or heroin products within the past 12 months; - Has a positive test for antibody to human immunodeficiency virus (HIV-1 or -2); - Has a positive test for hepatitis B surface antigen (HbsAg); - Has a hemoglobin (Hb) <13 g/dL for males or <12 g/dL for females; - Has an absolute neutrophil count (ANC) <1,500/mm3; - Has a platelet count <100,000/mm3; - Has a serum creatinine >1.1x ULN; - Has a history of autoimmune or antibody-mediated diseases, including, but not limited to, the following: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren’s syndrome with demonstrable antibodies, and autoimmune thrombocytopenia; - Has a history of allogeneic organ transplant (including bone marrow or stem cells); - Has active depression uncontrolled by treatment, a history of attempting suicide, or a history of being hospitalized in the past 10 years for psychiatric illness (e.g., depression, schizophrenia, psychosis) ; - Has other significant medical disease (chronic or active within the past 6 months), including, but not limited to: cardiac disease (unstable angina, myocardial infarction, congestive heart failure, or ventricular arrhythmia); cancer; uncontrolled seizure disorder; encephalopathy; esophageal bleeding; ascites; chronic infection other than HCV (e.g., tuberculosis); uncontrolled diabetes; - Has received within the past three months or is expected to receive during the study period any of the following treatments: – Immunosuppressive drugs, including, but not limited to, cytotoxic agents, monoclonal antibodies (against cytokines or cell-associated antigens), calcineurin inhibitors (and related agents), systemic (oral or intravenous) corticosteroids. – Hematopoietic stimulating agents, including, but not limited to, erythropoietin, G-CSF, GM-CSF. – Warfarin >1 mg/day – Another investigational drug. - Has planned, or is expected to require, during the study period, any surgery requiring general anesthesia; - Has any other condition that would, in the opinion of the Investigator, potentially compromise the safety or compliance of the patient or may preclude the patient’s successful completion of the clinical trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The endpoints defined after 12 weeks of treatment are virologic response (VR; at least a 2 log10 decrease in HCV RNA viral load compared with pretreatment) and early virologic response (EVR; undetectable HCV RNA). The effect of treatment on HCV viral load will be assessed for the Per Protocol population by comparing the proportion of subjects achieving the following end points in each IMO-2125 arm with that for peg-rIFN arm: – virologic response (VR): HCV RNA viral load at EOT at least 2 log10 less than the pretreatment baseline; – early virologic response (EVR): undetectable HCV RNA viral load at EOT. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |