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Trial record 35 of 488 for:    ALS (Amyotrophic Lateral Sclerosis)

Gilenya in Amyotrophic Lateral Sclerosis (ALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01786174
Recruitment Status : Completed
First Posted : February 7, 2013
Results First Posted : December 31, 2015
Last Update Posted : July 1, 2016
Sponsor:
Collaborator:
ALS Therapy Development Institute
Information provided by (Responsible Party):
James D. Berry MD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Amyotrophic Lateral Sclerosis
Interventions Drug: Gilenya
Other: Placebo
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Gilenya (Fingolimod) Placebo
Hide Arm/Group Description

0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days

Gilenya: 0.5mg Gilenya orally by mouth once daily for approximately 28 days

0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days

Placebo: 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

Period Title: Overall Study
Started 18 10
Randomized 19 11
Completed 16 10
Not Completed 2 0
Reason Not Completed
Discontinued Study Drug             2             0
Arm/Group Title Gilenya (Fingolimod) Placebo Total
Hide Arm/Group Description

0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days

Gilenya: 0.5mg Gilenya orally by mouth once daily for approximately 28 days

0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days

Placebo: 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

Total of all reporting groups
Overall Number of Baseline Participants 18 10 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 10 participants 28 participants
56.4  (8.0) 55.1  (11.3) 55.9  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 10 participants 28 participants
Female
8
  44.4%
5
  50.0%
13
  46.4%
Male
10
  55.6%
5
  50.0%
15
  53.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 10 participants 28 participants
Hispanic or Latino
1
   5.6%
1
  10.0%
2
   7.1%
Not Hispanic or Latino
17
  94.4%
9
  90.0%
26
  92.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 10 participants 28 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
  20.0%
2
   7.1%
White
18
 100.0%
8
  80.0%
26
  92.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants 10 participants 28 participants
18 10 28
Months Since Symptom Onset  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 18 participants 10 participants 28 participants
12.6  (4.8) 15.0  (6.2) 13.5  (5.3)
Months Since Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 18 participants 10 participants 28 participants
5.5  (3.9) 6.0  (4.0) 5.7  (3.9)
El Escorial Criteria (EEC)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 10 participants 28 participants
Definite 11 4 15
Probable 6 3 9
Probable Laboratory Supported 1 3 4
[1]
Measure Description: El Escorial Criteria (EEC) lists out the criteria for the diagnosis of Amyotrophic Lateral Sclerosis utilizing clinical, electrophysiological or neuropathic examinations.
Bulbar Onset  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 10 participants 28 participants
Bulbar Onset 2 4 6
Other 16 6 22
Riluzole Usage at Screening  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 18 participants 10 participants 28 participants
On riluzole at screening 11 6 17
Not on riluzole at screening 7 4 11
Forced Expiratory Volume (FEV1) (max %-predicted)   [1] 
Mean (Standard Deviation)
Unit of measure:  % of Predicted Max Value
Number Analyzed 18 participants 10 participants 28 participants
83.5  (16.1) 81.4  (27.9) 82.8  (20.6)
[1]
Measure Description: Forced Expiratory Volume (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. It will be measured using procedures analogous to those described for the upright SVC.
ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a Scale
Number Analyzed 18 participants 10 participants 28 participants
38.8  (4.1) 37.9  (5.8) 38.5  (4.7)
[1]
Measure Description: The ALSFRS-R is a quickly administered (5 min) ordinal rating scale used to determine a subject's assessment of their capability and independence in 12 functional activities. There are 12 questions, graded by the subject 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.
Slow Vital Capacity (max %-predicted)   [1] 
Mean (Standard Deviation)
Unit of measure:  % of Predicted Max Value
Number Analyzed 18 participants 10 participants 28 participants
92.8  (18.5) 82.8  (21.9) 89.2  (20.0)
[1]
Measure Description: The vital capacity (VC) (percent of predicted normal) was determined using the slow VC method. Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal.
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilograms/meter^2 (kg/m^2)
Number Analyzed 18 participants 10 participants 28 participants
26.1  (3.0) 26.3  (4.9) 26.2  (3.7)
1.Primary Outcome
Title ALSFRS-R Total Score at Weeks 0, 2, 4 and 8
Hide Description The ALSFRS-R is a quickly administered (5 minutes) ordinal rating scale (ratings 0-4) used to determine subjects' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, was closely associated with quality of life measures, and predicted survival.
Time Frame Week 0, Week 2, Week 4 and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
The reported results are model estimates from a model that estimates a single baseline value across all randomized participants, i.e., reflecting the true state of the population prior to randomization.
Arm/Group Title Gilenya (Fingolimod) Placebo
Hide Arm/Group Description:

0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days

Gilenya: 0.5mg Gilenya orally by mouth once daily for approximately 28 days

0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days

Placebo: 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

Overall Number of Participants Analyzed 18 10
Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
Week 0
38.60
(36.4 to 40.8)
38.60
(36.4 to 40.8)
Week 2
38.15
(35.8 to 40.5)
38.29
(35.8 to 40.8)
Week 4
38.03
(35.6 to 40.5)
37.88
(35.3 to 40.5)
Week 8
36.74
(34.1 to 39.4)
37.10
(34.2 to 40.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilenya (Fingolimod), Placebo
Comments Fingolimod vs. Placebo Weeks 0-4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.780
Comments [Not Specified]
Method Random slopes model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-1.53 to 2.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.89
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change in Slow Vital Capacity Score (SVC)
Hide Description The vital capacity (VC) (percent of predicted normal) was determined using the slow VC method. Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal.
Time Frame Week 0, Week 2, Week 4 and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Gilenya (Fingolimod) Placebo
Hide Arm/Group Description:

0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days

Gilenya: 0.5mg Gilenya orally by mouth once daily for approximately 28 days

0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days

Placebo: 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

Overall Number of Participants Analyzed 18 10
Mean (95% Confidence Interval)
Unit of Measure: Percentage of predicted max value
Week 0
88.28
(84.9 to 91.7)
88.28
(84.9 to 91.7)
Week 2
88.54
(85.8 to 91.3)
88.54
(85.8 to 91.3)
Week 4
86.51
(83.4 to 89.6)
86.70
(82.6 to 90.8)
Week 8
86.02
(83.1 to 89.0)
87.59
(83.4 to 91.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilenya (Fingolimod), Placebo
Comments Fingolimod vs. Placebo Weeks 0-4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.823
Comments [Not Specified]
Method Random slopes model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-5.00 to 3.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.26
Estimation Comments [Not Specified]
3.Primary Outcome
Title Forced Expiratory Volume in 1 Second (FEV1)
Hide Description Forced Expiratory Volume (FEV1): Forced Expiratory Volume (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Time Frame Screening, Week 0, Week 2, and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The reported results are model estimates from a model that estimates a single baseline value across all randomized participants, i.e., reflecting the true state of the population prior to randomization.
Arm/Group Title Gilenya (Fingolimod) Placebo
Hide Arm/Group Description:

0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days

Gilenya: 0.5mg Gilenya orally by mouth once daily for approximately 28 days

0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days

Placebo: 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

Overall Number of Participants Analyzed 18 10
Mean (95% Confidence Interval)
Unit of Measure: Percentage of predicted max value
Screening
84.70
(78.7 to 90.7)
84.70
(78.7 to 90.7)
Week 0
81.93
(76.3 to 87.5)
81.93
(76.3 to 87.5)
Week 2
81.19
(74.8 to 87.5)
80.30
(72.9 to 87.7)
Week 4
80.38
(73.3 to 87.5)
78.16
(69.5 to 86.8)
4.Secondary Outcome
Title Lymphocyte (T-Cell) Subset Trajectories
Hide Description Gilenya (fingolimod) has been shown to successfully reduce circulating lymphocytes (a type of white blood cell) by blocking their egress (exit) from the lymph nodes. A secondary objective of the study is to quantify the effect of the treatment on circulating lymphocyte populations in patients with ALS.
Time Frame Week 0, Week 2, and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Gilenya (Fingolimod) Placebo
Hide Arm/Group Description:

0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days

Gilenya: 0.5mg Gilenya orally by mouth once daily for approximately 28 days

0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days

Placebo: 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

Overall Number of Participants Analyzed 18 10
Mean (95% Confidence Interval)
Unit of Measure: 10^3/uL
Week 0
1.751
(1.527 to 2.008)
1.751
(1.572 to 2.008)
Week 2
0.580
(0.491 to 0.685)
1.732
(1.402 to 2.140)
Week 4
0.499
(0.399 to 0.623)
1.822
(1.357 to 2.447)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilenya (Fingolimod), Placebo
Comments Fingolimod vs. Placebo Weeks 0-4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.746
Comments [Not Specified]
Method Random slopes model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.40
Confidence Interval (2-Sided) 95%
-7.17 to 9.96
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.30
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio
Hide Description

Forced Expiratory Volume (FEV1): Forced Expiratory Volume (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.

Slow Vital Capacity (SVC): Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal.

Time Frame Screening, Week 0, Week 2, and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The reported results are model estimates from a model that estimates a single baseline value across all randomized participants, i.e., reflecting the true state of the population prior to randomization.
Arm/Group Title Gilenya (Fingolimod) Placebo
Hide Arm/Group Description:

0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days

Gilenya: 0.5mg Gilenya orally by mouth once daily for approximately 28 days

0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days

Placebo: 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

Overall Number of Participants Analyzed 18 10
Mean (95% Confidence Interval)
Unit of Measure: Percentage of predicted max value
Screening
77.39
(70.0 to 84.8)
77.39
(70.0 to 84.4)
Week 0
74.36
(67.9 to 80.8)
74.36
(67.9 to 80.8)
Week 2
75.46
(69.0 to 81.9)
73.14
(65.7 to 80.6)
Week 4
76.34
(69.7 to 83.0)
71.49
(63.3 to 79.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gilenya (Fingolimod), Placebo
Comments Fingolimod vs. Placebo Weeks 0-4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.294
Comments [Not Specified]
Method Random slopes model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 4.27
Confidence Interval (2-Sided) 95%
-3.78 to 12.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.04
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Gilenya (Fingolimod) Placebo
Hide Arm/Group Description

0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days

Gilenya: 0.5mg Gilenya orally by mouth once daily for approximately 28 days

0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days

Placebo: 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

All-Cause Mortality
Gilenya (Fingolimod) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Gilenya (Fingolimod) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      0/10 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Gilenya (Fingolimod) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/18 (83.33%)      8/10 (80.00%)    
Cardiac disorders     
Blood pressure increase *  1/18 (5.56%)  1 0/10 (0.00%)  0
Bradycardia *  3/18 (16.67%)  3 0/10 (0.00%)  0
Electrocardiogram QT prolonged *  1/18 (5.56%)  1 0/10 (0.00%)  0
Eye disorders     
Eye haemorrhage *  1/18 (5.56%)  1 0/10 (0.00%)  0
Gastrointestinal disorders     
Bowel movement irregularity *  0/18 (0.00%)  0 1/10 (10.00%)  1
Diarrhoea *  0/18 (0.00%)  0 1/10 (10.00%)  1
Flatulence *  0/18 (0.00%)  0 1/10 (10.00%)  1
Gastroesophageal reflux disease *  0/18 (0.00%)  0 1/10 (10.00%)  1
Nausea *  1/18 (5.56%)  1 0/10 (0.00%)  0
Salivary hypersecretion *  0/18 (0.00%)  0 1/10 (10.00%)  1
Vomiting *  1/18 (5.56%)  1 0/10 (0.00%)  0
General disorders     
Fatigue *  4/18 (22.22%)  5 3/10 (30.00%)  3
Non-cardiac chest pain *  0/18 (0.00%)  0 1/10 (10.00%)  1
Infections and infestations     
Incision site infection *  1/18 (5.56%)  1 0/10 (0.00%)  0
Nasopharyngitis *  1/18 (5.56%)  2 1/10 (10.00%)  1
Injury, poisoning and procedural complications     
Ankle fracture *  1/18 (5.56%)  1 0/10 (0.00%)  0
Excoriation *  0/18 (0.00%)  0 1/10 (10.00%)  1
Fall *  6/18 (33.33%)  7 1/10 (10.00%)  1
Soft tissue injury *  1/18 (5.56%)  1 0/10 (0.00%)  0
Thermal burn *  0/18 (0.00%)  0 1/10 (10.00%)  2
Musculoskeletal and connective tissue disorders     
Muscular weakness *  3/18 (16.67%)  3 2/10 (20.00%)  2
Musculoskeletal pain *  0/18 (0.00%)  0 1/10 (10.00%)  1
Nervous system disorders     
Dizziness *  1/18 (5.56%)  1 1/10 (10.00%)  1
Dysarthria *  0/18 (0.00%)  0 1/10 (10.00%)  1
Dysgeusia *  1/18 (5.56%)  1 0/10 (0.00%)  0
Headache *  4/18 (22.22%)  4 2/10 (20.00%)  3
Psychiatric disorders     
Insomnia *  1/18 (5.56%)  1 1/10 (10.00%)  1
Renal and urinary disorders     
Ketonuria *  0/18 (0.00%)  0 1/10 (10.00%)  1
Proteinuria *  0/18 (0.00%)  0 1/10 (10.00%)  1
Respiratory, thoracic and mediastinal disorders     
Cough *  2/18 (11.11%)  2 0/10 (0.00%)  0
Sinus congestion *  0/18 (0.00%)  0 1/10 (10.00%)  1
Throat irritation *  1/18 (5.56%)  1 0/10 (0.00%)  0
Surgical and medical procedures     
Lesion excision *  1/18 (5.56%)  1 0/10 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: James D. Berry, MD, MPH
Organization: Massachusetts General Hospital
Phone: 617-726-5097
Responsible Party: James D. Berry MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01786174     History of Changes
Other Study ID Numbers: 2013P000313
First Submitted: February 4, 2013
First Posted: February 7, 2013
Results First Submitted: October 23, 2015
Results First Posted: December 31, 2015
Last Update Posted: July 1, 2016