E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paraneoplastic Neurological Syndromes associated with anti-Hu antibodies |
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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 | 10014619 |
E.1.2 | Term | Encephalomyelitis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the trial is to study the efficacy of sirolimus in paraneoplastic neurological syndromes associated with anti-Hu antibodies.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to correlate clinical improvement with anti-Hu antibody titers in serum and cerebrospinal fluid (CSF), HuD specific T cells in blood and CSF, sirolimus levels in blood and CSF and with MDR1 polymorphism. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
i) PEM/PSN associated with high (>=1:400 by IIF) titer anti-Hu antibodies. ii) IIF (indirect immunofluorescence) has been confirmed by Western blotting using purified HuD fusion protein as substrate. iii) The neurological symptoms must still be progressing defined as neurological deterioration over the last 4 weeks. iv) Patients aged >=18 years. v) Patients who receive or will receive concomitant anti-tumor therapy are allowed to participate. vi) Patients who have given written informed consent.
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E.4 | Principal exclusion criteria |
i) Patients who have reached a neurological plateau phase more than 4 weeks before inclusion date (‘damage is done’). ii) Patients who are unwilling to undergo lumbar puncture. iii) Liver enzyme elevations of more than 5-fold normal values iv) Renal failure (GFR < 30 ml/min) v) Extreme hypertriglyceridemia (> 10 mmol/L) and extreme hypercholesterolemia (> 10 mmol/L) vi) Active infection vii) Women of childbearing potential who are pregnant or lactating, seeking pregnancy or failing to take adequate contraceptive precautions.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the functional and neurological improvement after 8 weeks of sirolimus. Functional improvement is defined as an decrease of one point or more on the Rankin scale after the 8th week of sirolimus as compared to the baseline evaluation. Improvement of neurological impairment is defined as a positive score (>0) in the EFIT overall evaluation after the 8th week of sirolimus as compared to the baseline evaluation. |
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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 | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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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 |