E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic inflammatory demyelinating polyneuropathy (CIDP) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057645 |
E.1.2 | Term | Chronic inflammatory demyelinating polyradiculoneuropathy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 |
To evaluate the effect of fingolimod 0.5 mg daily compared with placebo on delaying disability progression, in patients with CIDP, measured by the time to the first confirmed worsening on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale. A confirmed worsening is defined as an increase by 1 point or more on the adjusted INCAT Disability Scale from the value at Baseline. |
|
E.2.2 | Secondary objectives of the trial |
• to assess the change in grip strength from Baseline to Month 6/End-of-Treatment (whichever occurs first) in CIDP patients on fingolimod as compared with those on placebo
• to assess the change in Rasch-Built Linearly Weighted Overall Disability Scale (R-ODS) from Baseline to Month 6/End-of-Treatment (whichever occurs first) in CIDP patients on fingolimod as compared with those on placebo
• to evaluate safety and tolerability of fingolimod compared with placebo in patients with CIDP |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria
1. written informed consent must be obtained before any assessment is
performed
2. The diagnosis of CIDP will use the definition of the the European
Federation of Neurological Societies/Peripheral Nerve Society
(EFNS/PNS) Task Force First Revision. Patients must either have a
clinical diagnosis of CIDP fulfilling the clinical inclusion criteria for
typical CIDP or one of the following forms of atypical CIDP:
•pure motor, or
•asymetrical [MADSAM(Lewis-Sumner syndrome)], or
• IgA or IgG (not IgM) MGUS paraprotein associated
All patients must also fulfill the clinical exclusion criteria and the definite
electrodiagnostic criteria of the EFNS/PNS Task Force First Revision (Van
den Bergh et al 2010 and Erratum 2011)
3. disability defined by an INCAT Disability Scale score of 1-9 or, if INCAT
score is 0, a
documented history of disability sufficient to require treatment within
the past 2 years
following reduction or interruption of CIDP treatment
4. receiving IVIg treatment (minimal dose equivalent to 0.4 g/kg every 4
weeks for a minimum of 12 weeks) or corticosteroids (minimal dose
equivalent to prednisone 10 mg/day) treatment prior to the screening
visit
5. History of documented clinically meaningful deterioration confirmed by clinical examination, during therapy or upon interruption or reduction of therapy within 18 months prior to screening
6. Stable CIDP symptoms without significant change in treatment regimen for the 6 weeks before randomization
7. male or female aged 18 years or older at screening |
|
E.4 | Principal exclusion criteria |
Exclusion Criteria
1. other chronic demyelinating neuropathies, including: • Distal Acquired Demyelinating Symmetric Neuropathy (DADS) • Multifocal Motor Neuropathy with conduction block (MMN) • pure sensory CIDP • hematopoietic malignancy except for MGUS IgG or IgA
2. conditions in which the pathogenesis of the neuropathy may be different from CIDP such as: Lyme disease, POEMS syndrome, osteosclerotic myeloma, Castleman’s
disease
3. treatment with: • plasma exchange
within 2 months of randomization •
immunosuppressive/chemotherapeutic
medications: • azathioprine, cyclophosphamide, cyclosporine, mycophenolate, etanercept, methotrexate, tacrolimus or other immunosuppressive drugs within 6 months of randomization or 5 half-lives (whichever is later)
• Rituximab in the 2 years prior to randomization; patients that have
received rituximab between 1 and 2 years prior to randomization should
have B-cell (CD19/CD20) testing performed and if values are within
normal range, patients are eligible to participate
4. a CIDP relapse or significant worsening of symptoms within 2 months of randomization. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Delay of disease progression, measured by time to first confirmed worsening on the adjusted INCAT disability scale by 1 point or more from the value at baseline, in patients who were being treated with IVIG and/or corticosteroids prior to study start. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1) The change in grip strength from baseline in CIDP patients on fingolimod as compared with those on placebo. Grip strength measurements will be done using a vigorimeter
2) The change from baseline for Rasch-Built Linearly Weighted Overall Disability Scale (R-ODS). This questionnaire was constructed using the patients perception of their ability to perform daily and social activities
3) Safety and tolerability of fingolimod compared with placebo in patients with CIDP. Measured by AE/SAE, hematology and biochemistry lab tests, vital signs, ECG, and pulmonary function test. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Month 6/ End of treatment
2) Month 6/ End of treatment
3) End of study |
|
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 | 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) | Yes |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Australia |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Greece |
Israel |
Italy |
Japan |
Netherlands |
Norway |
Poland |
Spain |
United Kingdom |
United States |
|
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |