Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Conditions
Keywords
chronic inflammatory demyelinating polyradiculoneuropathy, CIDP, FTY720, fingolimod.
Brief summary
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
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.
Interventions
DRUGPlacebo Comparator
Matching placebo capsules
DRUGFingolimod
Fingolimod 0.5 mg capsules
Sponsors
Tanabe Pharma Corporation
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Confirmed Worsening on the Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale | Month 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for Grip Strength, Dominant Hand | baseline, Month 6, Month 12 | 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. |
| Change From Baseline for Grip Strength, Non-dominant Hand | baseline, Month 6, Month 12 | 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. |
| Change From Baseline for Rasch-Built Linearly Weighted Overall Disability Scale (R-ODS) | baseline, Month 6, Month 12 | 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. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Greece, Israel, Italy, Japan, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Participants were assigned randomly to each treatment group in a 1:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Fingolimod (FTY720) Participants received Fingolimod 0.5 mg orally once daily. | 54 |
| Placebo Participants received matching placebo to Fingolimod orally once daily. | 52 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 1 | 0 |
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lack of Efficacy | 12 | 8 |
| Overall Study | Protocol deviation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | Fingolimod (FTY720) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.3 Years STANDARD_DEVIATION 13.32 | 54.6 Years STANDARD_DEVIATION 11.68 | 54.5 Years STANDARD_DEVIATION 12.48 |
| Sex: Female, Male Female | 17 Participants | 22 Participants | 39 Participants |
| Sex: Female, Male Male | 37 Participants | 30 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 40 / 54 | 42 / 52 | 82 / 106 |
| serious Total, serious adverse events | 9 / 54 | 4 / 52 | 13 / 106 |
Outcome results
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.
Time frame: Month 12
Population: The full analysis set, which included all participants who were assigned randomly to receive treatment, was analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fingolimod (FTY720) | Time to First Confirmed Worsening on the Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale | 721.0 Days |
| Placebo | Time to First Confirmed Worsening on the Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Scale | 540.0 Days |
p-value: 0.983895% CI: [0.6, 1.7]Regression, Cox
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.
Time frame: baseline, Month 6, Month 12
Population: Only participants from the FAS, who had non-missing baseline values and the given post-baseline values, were included in the analysis. The FAS included all participants who were assigned randomly to receive treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Fingolimod (FTY720) | Change From Baseline for Grip Strength, Dominant Hand | Month 6 | -2.6 kPa |
| Fingolimod (FTY720) | Change From Baseline for Grip Strength, Dominant Hand | Month 12 | -0.8 kPa |
| Placebo | Change From Baseline for Grip Strength, Dominant Hand | Month 6 | -3.8 kPa |
| Placebo | Change From Baseline for Grip Strength, Dominant Hand | Month 12 | -3.9 kPa |
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.
Time frame: baseline, Month 6, Month 12
Population: Only participants from the FAS, who had non-missing baseline values and the given post-baseline values, were included in the analysis. The FAS included all participants who were assigned randomly to receive treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Fingolimod (FTY720) | Change From Baseline for Grip Strength, Non-dominant Hand | Month 12 | -1.2 kPa |
| Fingolimod (FTY720) | Change From Baseline for Grip Strength, Non-dominant Hand | Month 6 | -2.7 kPa |
| Placebo | Change From Baseline for Grip Strength, Non-dominant Hand | Month 12 | -5.0 kPa |
| Placebo | Change From Baseline for Grip Strength, Non-dominant Hand | Month 6 | -6.1 kPa |
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.
Time frame: baseline, Month 6, Month 12
Population: Only participants from the FAS, who had non-missing baseline values and the given post-baseline values, were included in the analysis. The FAS included all participants who were assigned randomly to receive treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Fingolimod (FTY720) | Change From Baseline for Rasch-Built Linearly Weighted Overall Disability Scale (R-ODS) | Month 6 | -6.4 score on a scale |
| Fingolimod (FTY720) | Change From Baseline for Rasch-Built Linearly Weighted Overall Disability Scale (R-ODS) | Month 12 | -5.7 score on a scale |
| Placebo | Change From Baseline for Rasch-Built Linearly Weighted Overall Disability Scale (R-ODS) | Month 6 | -5.5 score on a scale |
| Placebo | Change From Baseline for Rasch-Built Linearly Weighted Overall Disability Scale (R-ODS) | Month 12 | -5.1 score on a scale |