E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic hepatitis B virus infection |
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MedDRA Classification |
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 assess the safety of M04NM11 compared to placebo, when administered orally in escalating doses, of 108 CFU, 109 CFU and 1010 CFU, up to a maximum total of 6 doses, 28 days apart, over a 6 month period, to patients that are chronic carriers of the hepatitis B virus (HBV). |
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E.2.2 | Secondary objectives of the trial |
To assess the proportion of patients who are chronic carriers of HBV who experience a reduction in HBV DNA load during treatment with up to 6 doses of M04NM11. A decrease of ≥ 2 log10 or a reduction to < 104 copies/mL will be considered clinically significant.
To explore whether any patients who are HBeAg positive become HBeAg negative over the course of the study.
To explore whether any patients become anti-HBe positive during the study.
To explore whether any patients experience a reduction in ALT levels to within the normal range.
To explore whether any patients mount an immune response of a Th1 type by quantitation of antigen specific T cells that produce IFN-g to HBcAg as assessed by ELISPOT and intracellular cytokine staining.
To evaluate the post treatment effects of M04NM11 in the 6-month period following completion of dosing. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Able and willing to give written informed consent 2. Aged 18 years or older. 3. HBsAg positive for at least 6 months (with 2 separate positive test results at least 3 months apart). 4. a) 15 patients must be HBeAg positive with low ALT (≤2 x ULN) and HBV DNA load ≥106 copies/mL (Group 1). b) 15 patients must be HBeAg positive, with high ALT (>2 x ULN and ≤5 x ULN) and HBV DNA load ≥106 copies/mL (Group 2). c) 15 patients must be HBeAg negative, with high ALT (>2 x ULN and ≤5 x ULN) and HBV DNA >105 copies/mL (Group 3). 5. Have a detailed medical history demonstrating stable ALT, PT and serum bilirubin with at least 2 readings in the previous 6 months and including a liver biopsy in the previous 24 months. 6. Available for the duration of the study and for unscheduled visits. |
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E.4 | Principal exclusion criteria |
The following summarises the criteria that will exclude patients:Patients who have a history of anaphylaxis or hypersensitivity to the components of M04NM11, a known impairment of the immune system (HIV positive, immunosuppressant therapy or cytotoxic therapy). Patients with autoimmune diseases or hepatitis C or D. Patients with ALT >5.1x ULN, PT >1.25 x ULN or total bilirubin >1.5 x ULN. Patients who have evidence of hepatic decompensation. Patient who have had a liver biopsy with evidence of cirrhosis in the last 24 months. Patients who are involved in or have completed a clinical trial for hepatitis B within the previous 12 months, or for other conditions within the previous 3 months. Current or previous therapy with immunotherapies or anti-viral medications for hepatitis B in the last 12 months. Patients who have had a recent infection requiring antibiotics in the 7 days prior to dosing, or with hypersensitivity to ciprofloxacin, trimethoprim-sulfamethoxazole, or related antibiotics. Patients who have significantly abnormal laboratory findings, with the exception of LFTs as defined above, or have problems with addiction. Patients who work as food handlers, or health-care workers with direct contact with high-risk patients, or child-care workers with routine contact with children less than 2 years of age. Pregnant or breast feeding patients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The incidence of clinically significant changes in serum biochemistry and haematology tests, particularly elevations of ALT or bilirubin, or prolongation of PT.
The incidence of adverse events, including flu-like symptoms, attributable to the investigational product.
The incidence of serious adverse events attributable to the investigational product |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Dose escalation within each patient |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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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End of trial is defined as date of last visit of 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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |