E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of patients with chronic genotype 1 hepatitis C |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
The primary objective is to evaluate the efficacy of TG4040 combined with SOC (Peg-IFN alfa2a and RBV) in treatment-naïve patients with chronic genotype 1 hepatitis C infection as measured by the proportion of patients who achieve complete early virologic response (cEVR is defined as undetectability of the HCV RNA after 12 weeks of SOC). |
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E.2.2 | Secondary objectives of the trial |
- The evaluation of the effects of TG4040 alone or combined with SOC on viral load, over time, relative to baseline including but not restricted to RVR, EVR, ETR and SVR.
- The evaluation of the safety of TG4040 alone and in combination with SOC.
- The determination of the immunogenicity of TG4040 alone and in combination with SOC.
- The identification of molecular biomarkers related to TG4040 efficacy in combination with SOC by gene expression profiling.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients, age ≥18 to ≤ 70 years;
- Chronically infected patients with Hepatitis C virus Genotype 1 (1a or 1b) with detectable viremia (HCV RNA in blood) for more than 6 months and naïve to treatment;
- Patients must have compensated liver disease, with no history of ascites, jaundice, hepatic encephalopathy or bleeding from esophageal or gastric varices requiring beta-blockers;
- No histological evidence of hepatic cirrhosis (including compensated cirrhosis) based on a liver biopsy taken within 24 months prior to baseline; or on a FibroScan® performed within 6 months prior to treatment which indicates the absence of liver cirrhosis, i.e., stage < F4 (METAVIR) or 12 kPa; in case of no available results, a liver biopsy will be performed prior to treatment;
- All laboratory parameters must be grade 0 or 1 (as per CTCAE criteria) except for alanine amino-transferase (ALT), aspartate amino-transferase (AST), gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) for which a grade 2 will be allowed if stated non clinically significant;
- No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBsAg positive);
- No intravenous (IV) drug or alcohol abuse;
- Serum thyroid stimulating hormone (TSH) levels within normal ranges, regardless of treatment with L-thyroxin;
- Normal electrocardiogram (ECG);
- Normal retinal examination (eye fundus) within last 12 months for diabetic patients or patients suffering from high blood pressure;
- Negative pregnancy test in women of childbearing potential (a woman who is two years post-menopausal or surgically sterile is not considered to be of childbearing potential);
- Female patients and female partners of male patients (if childbearing potency) must agree to use two effective methods of birth control during the study and for 6 months after the end of treatment. One of the methods needs to be a 'barrier' method (condom or diaphragm);
- Written informed consent.
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E.4 | Principal exclusion criteria |
- Prior treatment for hepatitis C;
- Malignancy within the last 5 years; except for patients with history of squamous cell skin cancer or basal cell skin cancer who will be enrolled, unless patients have a history of skin cancer at the vaccination site;
- Diagnosed or suspected hepatocellular carcinoma;
- History of psychiatric conditions including, but not limited to, psychosis, suicidal ideations, or major depression. Patients with mild to moderate depression in the past and no prior history of suicidal gestures or attempts may be enrolled if, in the Investigator’s opinion, they are suitable for treatment;
- Serious, concomitant medical disorder, including active systemic infection and proven or suspected immunosuppressive disorder;
- History of immunodeficiency or autoimmune disease including autoimmune hepatitis, allogenic 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;
- Administration of any vaccine or immunoglobulin within 30 days before the first dose of TG4040 /SOC;
- 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);
- Systemic corticosteroid therapy or other immunosuppressive/immunomodulating drugs (e.g. Cyclosporine) within 2 months prior to first TG4040/SOC administration; corticosteroid nasal sprays, inhaled steroids for asthma and/or topical steroids are allowed;
- Any known allergy to interferon (IFN), RBV and/or their excipients;
- Any medical contraindications to IFN and/or RBV;
- Any known allergy to gentamycin, to bovine serum albumin, to eggs;
- Women who are breastfeeding;
- Participation in another experimental therapeutic protocol within 6 months prior to baseline and during the study period;
- Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study;
- Patient unable or unwilling to comply with the protocol requirements.
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: percentage of patients achieving cEVR, defined as undetectable HCV RNA (less than 10 IU/mL, as measured by the Roche TaqMan(R) assay) 12 weeks after the start of SOC. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- determine the effects of TG4040 alone and in combination with SOC on viral load, relative to baseline (over time and at specific endpoints, and slope of second phase viral dynamic clearance between week 4 and week 12 of SOC);
- evaluate the safety of TG4040 alone and in combination with SOC (during the course of the study);
- determine the immunogenicity of TG4040 alone and in combination with SOC (specific timepoints);
- identify molecular biomarkers related to TG4040 efficacy in combination with SOC by gene expression profiling (specific timepoints).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
PR2 + PR3 (HCV current SOC) |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 31 |
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 | No |
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 | Yes |
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. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |