Evaluate Efficacy and Safety of Fingolimod 0.5 mg Orally Once Daily Versus Placebo in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients.

Study Overview
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Brief Summary
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The study was designed to evaluate the efficacy and safety of fingolimod in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy compared with placebo.

Detailed Description
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This study was a double-blind, randomized, multicenter, placebo-controlled, parallel-group study in patients with a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy and treated with IVIg, corticosteroids, or both therapies prior to study entry. Patients meeting the eligibility criteria were randomly assigned in a ratio of 1:1 to receive oral fingolimod (0.5 mg/day) or matching placebo. The study consisted of 3 periods: a Screening Period, a Double-blind Treatment Period and a Follow-up Period after discontinuation of study drug treatment. Patients who complete the study will have an option to enter an extension.

Official Title
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A Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Fingolimod 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Conditions
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Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Intervention / Treatment
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* Drug: Fingolimod
* Drug: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria written informed consent must be obtained before any assessment is performed The diagnosis of CIDP will use the definition of the 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 atypical forms of CIDP: pure motor, or asymmetrical (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. 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 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 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 stable CIDP symptoms for the 6 weeks before randomization Exclusion Criteria other chronic demyelinating neuropathies, including: Distal Acquired Demyelinating Symmetric Neuropathy (DADS) Multifocal Motor Neuropathy (MMN) pure sensory CIDP hematopoietic malignancy except for MGUS conditions in which the pathogenesis of the neuropathy may be different from CIDP such as: Lyme disease, POEMS syndrome, osteosclerotic myeloma, Castleman's disease 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 should have B-cell levels within normal range), other cytotoxic immunosuppressive medications with sustained effects (including mitoxantrone, alemtuzumab, cladribine) at any time, hematopoietic stem cell transplantation at any time

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fingolimod (FTY720)<br>Participants received Fingolimod 0.5 mg orally once daily. | Drug: Fingolimod<br>* Fingolimod 0.5 mg capsules<br>|
| Placebo Comparator: Placebo<br>Participants received matching placebo to Fingolimod orally once daily. | Drug: Placebo Comparator<br>* Matching placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Confirmed Worsening on the Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale | Confirmed worsening in CIDP was measured by the adjusted INCAT Disability Scale. The adjusted INCAT disability scale measures arm disability and leg disability. For arm disability the scale ranges from 0 (no upper limb problems) to 5 (inability to use either arm for any purposeful movement). The leg disability scale ranges from 0 (walking not affected) to 5 (restricted to wheelchair, unable to stand and walk a few steps with help). The total adjusted INCAT disability score is calculated by the sum of the arm and leg disability scores where the total score ranges from 0 to 10. A confirmed worsening was defined as an increase by 1 or more points on the adjusted INCAT disability scale from the value at baseline. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline for Grip Strength, Dominant Hand | Grip strength measurements were done using a vigorimeter. With this device, the pressure in the bulb exercised by the participant was registered on a manometer via a rubber junction tube. Both the dominant and non-dominant hands were tested. A negative change from baseline indicates deterioration. | baseline, Month 6, Month 12 | 
| Change From Baseline for Grip Strength, Non-dominant Hand | Grip strength measurements were done using a vigorimeter. With this device, the pressure in the bulb exercised by the participant was registered on a manometer via a rubber junction tube. Both the dominant and non-dominant hands were tested. A negative change from baseline indicates deterioration. | baseline, Month 6, Month 12 | 
| 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. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The obtained raw summed score was translated subsequently to a convenient centile metric score ranging from 0 (most severe disability) to 100 (no disability at all). A higher score indicated a better health status. A negative change from baseline indicates deterioration. | baseline, Month 6, Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic inflammatory demyelinating polyradiculoneuropathy, CIDP, FTY720, fingolimod.