E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anti-Hu associated paraneoplastic neurological syndromes |
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E.1.1.1 | Medical condition in easily understood language |
Anti-Hu associated paraneoplastic neurological syndromes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
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 primary objective of this study is to investigate whether natalizumab results in functional improvement |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives: neurological improvement defined as a positive score (>0) in the EFIT overall evaluation and improvement on the AMC linear disability scale, Barthel index and PNS neurological scale after three natalizumab infusions (the 12th week of natalizumab), compared to baseline.
Translational Objectives:
a) detection of HuD-specific T-lymphocytes in blood and CSF;
b) phenotype of CSF cells (prior and after natalizumab) including B cells, T cells and DC;
c) anti-HuD titers in CSF and serum; and
d) single cell PCR on CSF derived plasma cells prior to treatment in order to determine the primary protein sequence of anti-HuD IgG.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- PEM/PSN associated with high titer (≥400) anti-Hu antibodies
- The neurological symptoms must still be progressing defined as neurological deterioration over the last 4 weeks
- Patients aged 18 years or older
- Patients with cancer related to Hu-Ab are allowed to participate
- Patients who receive or will receive anti-tumor therapy are allowed to participate
- Patients who have given written informed consent
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E.4 | Principal exclusion criteria |
- Patients who have reached a plateau phase more than 4 weeks before inclusion date (‘damage is done’)
- Patients who are unwilling to undergo lumbar puncture
- Hypersensitivity to natalizumab or one of the additives
- Progressive multifocal leukoencephalopathy (PML)
- Immune compromised patients (patients using immunosuppressive medications other than short course of steroids)
- Liver enzyme elevations of more than 5-fold normal values
- Renal failure (GFR < 30 ml/min)
- Active infection
- Women of childbearing potential who are pregnant or lactating, seeking pregnancy or failing to take adequate contraceptive precautions.
- Patients aged <18 years
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is functional improvement with one point or more on the modified Rankin scale (compared to baseline). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after first dose of natalizumab |
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E.5.2 | Secondary end point(s) |
Secondary endpoints include neurological improvement defined as a positive score (>0) in the EFIT overall evaluation and improvement on the AMC linear disability scale, Barthel index and PNS neurological scale after three natalizumab infusions compared to baseline
Translational endpoints are:
a) detection of HuD-specific T-lymphocytes in blood and CSF;
b) phenotype of CSF cells (prior and after natalizumab) including B cells, T cells and DC;
c) anti-HuD titers in CSF and serum; and
d) single cell PCR on CSF derived plasma cells prior to treatment in order to determine the primary protein sequence of anti-HuD IgG
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints: 12 weeks after first dose of natalizumab
Translational endpoints: before (t=0) and 12 weeks after first dose of natalizumab |
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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 | 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 | No |
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 | No |
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) | No |
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
| 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 | No |
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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End of study occurs after the follow-up assessment (8 weeks after last follow-up visit) of the last patient |
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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 |