E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C genotype 1 relapser |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | 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 NIM811 dosed daily for 4 weeks in combination with SOC (Part 1 only) • To evaluate, predicated on a successful outcome of Part 1, cohort A, the safety and efficacy of NIM811 dosed daily for 12 weeks in a population of HCV-1 infected, SOC relapser patients (Part 2 only) • To identify a dose of NIM811 which is safe and tolerated and produces in combination with SOC a clinically meaningful improvement over SOC monotherapy in antiviral response at the 12th week of dosing |
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E.2.2 | Secondary objectives of the trial |
• To assess the percentage of patients achieving rapid virologic response (RVR) in patients treated with NIM811 in combination with SOC. • To explore the pharmacokinetics and pharmacodynamics of NIM811 given in combination with SOC in patients with chronic hepatitis C genotype-1 • To evaluate the effect of NIM811 given in combination with SOC in patients with chronic hepatitis C on sustained virologic response at 24 weeks after the cessation of treatment (SVR24) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The role of cyclophilins and NS5B resistance mutations during 12 weeks of NIM811 treatment in HCV relapse patients (substudy only applicable to NL)
Hypotheses A 12 week course of treatment with NIM811 leads to 1) low levels of intra-cellular CypA and/ or CypB levels in T-cells leading to increased apoptosis rates 2) low concentrations of extra-cellular CypA leading to down-regulation of CD147 3) emergence of NS5B-mutations disrupts binding of NIM811 to CypA and/ or B leading to lower HCV replication and viral fitness.
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E.3 | Principal inclusion criteria |
o Chronic Hepatitis C infection Genotype 1 with documented histology and biochemical results consistent with compensated chronic hepatitis C. o HCV-RNA should be ≥ 4 x 100000 IU/mL at screening. o Male and female subjects from 18 to and including 69 years of age, with Chronic Hepatitis C genotype 1 o Recipient of prior long acting interferon (either as PegIntron, Pegasys or albumin-interferon alpha-2b) and ribavirin (either ribavirin or the ribavirin pro-drug, viramidine) treatment for at least 12 weeks, with documented negative serum HCV RNA on treatment , who subsequently becomes serum HCV RNA positive after stopping treatment (“relapser”). Patients must have been off all treatment for at least 3 months prior to start study(visit 1). Appropriate documentation of viral load will be provided in the patient’s source documentation for verification of relapse status o Platelets counts > 150,000/mm3 o No evidence of cirrhosis by any approved method: transient elastography, liver biopsy or Fibrotest, or any future approved validated method |
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E.4 | Principal exclusion criteria |
o Contraindication to either pegylated interferon or ribavirin o Pregnant or breast-feeding females o women of child bearing potential not willing to use 2 methods of contraception o Hepatic decompensation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Study part 1 is intended mainly for safety. The main end points will be adverse events and changes in laboratory values, in particular the change from baseline in platelet count observed at week 4. For study part 2, the primary end point is the drop from baseline in viral load to 12 week treatment. |
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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 | 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 | 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 | 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 |
adaptive design (dose response, safety, tolerability) |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Standard of Care (pegylated interferon and ribavirin) |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |