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

Chronic Inflammatory Demyelinating Polyradiculoneuropathy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01625182
• Other study ID #: CFTY720I2201
• Secondary ID: 2011-005280-24
• Status: Completed
• Phase: Phase 3
• First received: June 19, 2012
• Last updated: September 28, 2017
• Start date: December 22, 2012
• Est. completion date: September 3, 2016

Study information

• Verified date: September 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: September 3, 2016
• Est. primary completion date: September 3, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Inflammatory Demyelinating Polyradiculoneuropathy
• Polyradiculoneuropathy
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention

Drug:
• Fingolimod
Fingolimod 0.5 mg capsules
• Placebo Comparator
Matching placebo capsules

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Auchenflower	Queensland
Australia	Novartis Investigative Site	Fitzroy	Victoria
Australia	Novartis Investigative Site	Parkville	Victoria
Australia	Novartis Investigative Site	Sydney	New South Wales
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Canada	Novartis Investigative Site	Greenfield Park
Canada	Novartis Investigative Site	Kingston	Ontario
Canada	Novartis Investigative Site	Montreal
Canada	Novartis Investigative Site	Québec	Quebec
Czechia	Novartis Investigative Site	Praha 5
France	Novartis Investigative Site	Limoges
France	Novartis Investigative Site	Marseille cedex 05
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Pessac Cedex
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Düsseldorf
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Göttingen
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki
Greece	Novartis Investigative Site	Thessaloniki
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Cefalù	PA
Italy	Novartis Investigative Site	Ferrara
Italy	Novartis Investigative Site	Legnano	MI
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Pisa
Italy	Novartis Investigative Site	Rome
Italy	Novartis Investigative Site	Rozzano	MI
Japan	Novartis Investigative Site	Aomori
Japan	Novartis Investigative Site	Bunkyo	Tokyo
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Kodaira	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Sayama	Osaka
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Maastricht
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Lodz
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	L´Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	Madrid
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Headington	Oxfordshire
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Burlington	Vermont
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Orange	California
United States	Novartis Investigative Site	Patchogue	New York
United States	Novartis Investigative Site	Plainview	New York
United States	Novartis Investigative Site	Saint Petersburg	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Mitsubishi Tanabe Pharma Corporation

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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