Trial Outcomes & Findings for Gilenya in Amyotrophic Lateral Sclerosis (ALS) (NCT NCT01786174)
NCT ID: NCT01786174
Last Updated: 2016-07-01
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Week 0, Week 2, Week 4 and Week 8
Results posted on
2016-07-01
Participant Flow
Participant milestones
| Measure |
Gilenya (Fingolimod)
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
|
Placebo
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 Study
STARTED
|
18
|
10
|
|
Overall Study
Randomized
|
19
|
11
|
|
Overall Study
COMPLETED
|
16
|
10
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Gilenya (Fingolimod)
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
|
Placebo
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 Study
Discontinued Study Drug
|
2
|
0
|
Baseline Characteristics
Gilenya in Amyotrophic Lateral Sclerosis (ALS)
Baseline characteristics by cohort
| Measure |
Gilenya (Fingolimod)
n=18 Participants
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
|
Placebo
n=10 Participants
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
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.4 years
STANDARD_DEVIATION 8.0 • n=93 Participants
|
55.1 years
STANDARD_DEVIATION 11.3 • n=4 Participants
|
55.9 years
STANDARD_DEVIATION 9.1 • n=27 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=93 Participants
|
10 participants
n=4 Participants
|
28 participants
n=27 Participants
|
|
Months Since Symptom Onset
|
12.6 Months
STANDARD_DEVIATION 4.8 • n=93 Participants
|
15.0 Months
STANDARD_DEVIATION 6.2 • n=4 Participants
|
13.5 Months
STANDARD_DEVIATION 5.3 • n=27 Participants
|
|
Months Since Diagnosis
|
5.5 Months
STANDARD_DEVIATION 3.9 • n=93 Participants
|
6.0 Months
STANDARD_DEVIATION 4.0 • n=4 Participants
|
5.7 Months
STANDARD_DEVIATION 3.9 • n=27 Participants
|
|
El Escorial Criteria (EEC)
Definite
|
11 participants
n=93 Participants
|
4 participants
n=4 Participants
|
15 participants
n=27 Participants
|
|
El Escorial Criteria (EEC)
Probable
|
6 participants
n=93 Participants
|
3 participants
n=4 Participants
|
9 participants
n=27 Participants
|
|
El Escorial Criteria (EEC)
Probable Laboratory Supported
|
1 participants
n=93 Participants
|
3 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
Bulbar Onset
Bulbar Onset
|
2 participants
n=93 Participants
|
4 participants
n=4 Participants
|
6 participants
n=27 Participants
|
|
Bulbar Onset
Other
|
16 participants
n=93 Participants
|
6 participants
n=4 Participants
|
22 participants
n=27 Participants
|
|
Riluzole Usage at Screening
On riluzole at screening
|
11 participants
n=93 Participants
|
6 participants
n=4 Participants
|
17 participants
n=27 Participants
|
|
Riluzole Usage at Screening
Not on riluzole at screening
|
7 participants
n=93 Participants
|
4 participants
n=4 Participants
|
11 participants
n=27 Participants
|
|
Forced Expiratory Volume (FEV1) (max %-predicted)
|
83.5 % of Predicted Max Value
STANDARD_DEVIATION 16.1 • n=93 Participants
|
81.4 % of Predicted Max Value
STANDARD_DEVIATION 27.9 • n=4 Participants
|
82.8 % of Predicted Max Value
STANDARD_DEVIATION 20.6 • n=27 Participants
|
|
ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score
|
38.8 Score on a Scale
STANDARD_DEVIATION 4.1 • n=93 Participants
|
37.9 Score on a Scale
STANDARD_DEVIATION 5.8 • n=4 Participants
|
38.5 Score on a Scale
STANDARD_DEVIATION 4.7 • n=27 Participants
|
|
Slow Vital Capacity (max %-predicted)
|
92.8 % of Predicted Max Value
STANDARD_DEVIATION 18.5 • n=93 Participants
|
82.8 % of Predicted Max Value
STANDARD_DEVIATION 21.9 • n=4 Participants
|
89.2 % of Predicted Max Value
STANDARD_DEVIATION 20.0 • n=27 Participants
|
|
Body Mass Index (BMI)
|
26.1 kilograms/meter^2 (kg/m^2)
STANDARD_DEVIATION 3.0 • n=93 Participants
|
26.3 kilograms/meter^2 (kg/m^2)
STANDARD_DEVIATION 4.9 • n=4 Participants
|
26.2 kilograms/meter^2 (kg/m^2)
STANDARD_DEVIATION 3.7 • n=27 Participants
|
PRIMARY outcome
Timeframe: Week 0, Week 2, Week 4 and Week 8Population: 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.
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.
Outcome measures
| Measure |
Gilenya (Fingolimod)
n=18 Participants
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
|
Placebo
n=10 Participants
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
|
|---|---|---|
|
ALSFRS-R Total Score at Weeks 0, 2, 4 and 8
Week 0
|
38.60 scores on a scale
Interval 36.4 to 40.8
|
38.60 scores on a scale
Interval 36.4 to 40.8
|
|
ALSFRS-R Total Score at Weeks 0, 2, 4 and 8
Week 2
|
38.15 scores on a scale
Interval 35.8 to 40.5
|
38.29 scores on a scale
Interval 35.8 to 40.8
|
|
ALSFRS-R Total Score at Weeks 0, 2, 4 and 8
Week 4
|
38.03 scores on a scale
Interval 35.6 to 40.5
|
37.88 scores on a scale
Interval 35.3 to 40.5
|
|
ALSFRS-R Total Score at Weeks 0, 2, 4 and 8
Week 8
|
36.74 scores on a scale
Interval 34.1 to 39.4
|
37.10 scores on a scale
Interval 34.2 to 40.0
|
PRIMARY outcome
Timeframe: Week 0, Week 2, Week 4 and Week 8The 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.
Outcome measures
| Measure |
Gilenya (Fingolimod)
n=18 Participants
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
|
Placebo
n=10 Participants
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
|
|---|---|---|
|
Change in Slow Vital Capacity Score (SVC)
Week 0
|
88.28 Percentage of predicted max value
Interval 84.9 to 91.7
|
88.28 Percentage of predicted max value
Interval 84.9 to 91.7
|
|
Change in Slow Vital Capacity Score (SVC)
Week 2
|
88.54 Percentage of predicted max value
Interval 85.8 to 91.3
|
88.54 Percentage of predicted max value
Interval 85.8 to 91.3
|
|
Change in Slow Vital Capacity Score (SVC)
Week 4
|
86.51 Percentage of predicted max value
Interval 83.4 to 89.6
|
86.70 Percentage of predicted max value
Interval 82.6 to 90.8
|
|
Change in Slow Vital Capacity Score (SVC)
Week 8
|
86.02 Percentage of predicted max value
Interval 83.1 to 89.0
|
87.59 Percentage of predicted max value
Interval 83.4 to 91.8
|
PRIMARY outcome
Timeframe: Screening, Week 0, Week 2, and Week 4Population: 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.
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.
Outcome measures
| Measure |
Gilenya (Fingolimod)
n=18 Participants
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
|
Placebo
n=10 Participants
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
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1)
Screening
|
84.70 Percentage of predicted max value
Interval 78.7 to 90.7
|
84.70 Percentage of predicted max value
Interval 78.7 to 90.7
|
|
Forced Expiratory Volume in 1 Second (FEV1)
Week 0
|
81.93 Percentage of predicted max value
Interval 76.3 to 87.5
|
81.93 Percentage of predicted max value
Interval 76.3 to 87.5
|
|
Forced Expiratory Volume in 1 Second (FEV1)
Week 2
|
81.19 Percentage of predicted max value
Interval 74.8 to 87.5
|
80.30 Percentage of predicted max value
Interval 72.9 to 87.7
|
|
Forced Expiratory Volume in 1 Second (FEV1)
Week 4
|
80.38 Percentage of predicted max value
Interval 73.3 to 87.5
|
78.16 Percentage of predicted max value
Interval 69.5 to 86.8
|
SECONDARY outcome
Timeframe: Week 0, Week 2, and Week 4Gilenya (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.
Outcome measures
| Measure |
Gilenya (Fingolimod)
n=18 Participants
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
|
Placebo
n=10 Participants
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
|
|---|---|---|
|
Lymphocyte (T-Cell) Subset Trajectories
Week 0
|
1.751 10^3/uL
Interval 1.527 to 2.008
|
1.751 10^3/uL
Interval 1.572 to 2.008
|
|
Lymphocyte (T-Cell) Subset Trajectories
Week 2
|
0.580 10^3/uL
Interval 0.491 to 0.685
|
1.732 10^3/uL
Interval 1.402 to 2.14
|
|
Lymphocyte (T-Cell) Subset Trajectories
Week 4
|
0.499 10^3/uL
Interval 0.399 to 0.623
|
1.822 10^3/uL
Interval 1.357 to 2.447
|
SECONDARY outcome
Timeframe: Screening, Week 0, Week 2, and Week 4Population: 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.
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.
Outcome measures
| Measure |
Gilenya (Fingolimod)
n=18 Participants
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
|
Placebo
n=10 Participants
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
|
|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio
Week 2
|
75.46 Percentage of predicted max value
Interval 69.0 to 81.9
|
73.14 Percentage of predicted max value
Interval 65.7 to 80.6
|
|
Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio
Screening
|
77.39 Percentage of predicted max value
Interval 70.0 to 84.8
|
77.39 Percentage of predicted max value
Interval 70.0 to 84.4
|
|
Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio
Week 0
|
74.36 Percentage of predicted max value
Interval 67.9 to 80.8
|
74.36 Percentage of predicted max value
Interval 67.9 to 80.8
|
|
Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio
Week 4
|
76.34 Percentage of predicted max value
Interval 69.7 to 83.0
|
71.49 Percentage of predicted max value
Interval 63.3 to 79.7
|
Adverse Events
Gilenya (Fingolimod)
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Gilenya (Fingolimod)
n=18 participants at risk
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
|
Placebo
n=10 participants at risk
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
|
|---|---|---|
|
Cardiac disorders
Blood pressure increase
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Cardiac disorders
Bradycardia
|
16.7%
3/18 • Number of events 3
|
0.00%
0/10
|
|
Cardiac disorders
Electrocardiogram QT prolonged
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Eye disorders
Eye haemorrhage
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Bowel movement irregularity
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
General disorders
Fatigue
|
22.2%
4/18 • Number of events 5
|
30.0%
3/10 • Number of events 3
|
|
Infections and infestations
Incision site infection
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Infections and infestations
Nasopharyngitis
|
5.6%
1/18 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
33.3%
6/18 • Number of events 7
|
10.0%
1/10 • Number of events 1
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/18
|
10.0%
1/10 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
16.7%
3/18 • Number of events 3
|
20.0%
2/10 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
5.6%
1/18 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Nervous system disorders
Headache
|
22.2%
4/18 • Number of events 4
|
20.0%
2/10 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
5.6%
1/18 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Renal and urinary disorders
Ketonuria
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.1%
2/18 • Number of events 2
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/18
|
10.0%
1/10 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
|
Surgical and medical procedures
Lesion excision
|
5.6%
1/18 • Number of events 1
|
0.00%
0/10
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place