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Gilenya in Amyotrophic Lateral Sclerosis (ALS)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01786174
First Posted: February 7, 2013
Last Update Posted: July 1, 2016
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.
Collaborator:
ALS Therapy Development Institute
Information provided by (Responsible Party):
James D. Berry MD, Massachusetts General Hospital
  Purpose
The purpose of this study is to determine whether Gilenya, also known as fingolimod, is safe and tolerable in patients with Amyotrophic Lateral Sclerosis (ALS).

Condition Intervention Phase
Amyotrophic Lateral Sclerosis Drug: Gilenya Other: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IIa Double-Blind, Placebo-Controlled Study to Evaluate the Safety of Oral Fingolimod in Patients With Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:


Further study details as provided by James D. Berry MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • ALSFRS-R Total Score at Weeks 0, 2, 4 and 8 [ Time Frame: Week 0, Week 2, Week 4 and Week 8 ]
    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.

  • Change in Slow Vital Capacity Score (SVC) [ Time Frame: Week 0, Week 2, Week 4 and Week 8 ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Screening, Week 0, Week 2, and Week 4 ]
    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.


Secondary Outcome Measures:
  • Lymphocyte (T-Cell) Subset Trajectories [ Time Frame: Week 0, Week 2, and Week 4 ]
    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.

  • Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio [ Time Frame: Screening, Week 0, Week 2, and Week 4 ]

    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.



Enrollment: 30
Study Start Date: August 2013
Study Completion Date: May 2015
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gilenya (fingolimod)
0.5mg Gilenya (fingolimod) orally once daily for 28 days +/- 3 days
Drug: Gilenya
0.5mg Gilenya orally by mouth once daily for approximately 28 days
Other Name: fingolimod
Placebo Comparator: Placebo
0.5mg placebo (sugar pill) orally once daily for 28 days +/- 3 days
Other: Placebo
0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days

Detailed Description:

The primary objective of the study is to determine the acute safety and tolerability of oral administration of Gilenya (fingolimod) 0.5mg daily vs. matched oral placebo administered daily.

The primary outcome measure will be safety and tolerability; safety will be assessed by the occurrence of adverse events and clinically meaningful changes in vital signs, ophthalmologic examination, physical examination, electrocardiogram and standard clinical laboratory blood tests, and tolerability will be defined as the ability of subjects to complete the entire 4-week study.

The secondary outcome measure will be the measured effect of the treatment on circulating lymphocyte populations in patients with ALS.

Exploratory outcome measures will include the rate of decline of the ALS Functional Rating Scale (Revised) (ALSFRS-R) and Slow Vital Capacity (VC) during the course of treatment.

This study will be conducted in subjects who meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. At screening, eligible subjects must be at least 18 years old, must have an SVC ≥ 65% of predicted capacity for age, height and gender, and must provide written informed consent prior to screening. Subjects on a stable dose of riluzole and those not taking riluzole, and women of child-bearing age at screening are eligible for inclusion as long as they meet specific protocol requirements.

Subjects will remain on randomized, placebo-controlled, double-blind treatment until the Week 4 visit. Each randomized subject will also have a Week 8 Follow-up Telephone Interview to assess for adverse events (AEs), changes in concomitant medications and to administer the ALSFRS-R.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 years or older.
  2. Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
  3. Onset of weakness or spasticity due to ALS ≤ 2 years (24 months) prior to Baseline Visit.
  4. Slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and age at the screening visit.
  5. Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days, prior to randomization (riluzole-naïve subjects are permitted in the study).
  6. Subjects must be able to swallow oral medication at the Screening Visit and expected to be able to swallow the capsule throughout the course of the study.
  7. Capable of providing informed consent and following trial procedures.
  8. Geographically accessible to the site.
  9. Women must not be able to become pregnant (e.g. post menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and three months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal (patch or contraceptive ring, for example) contraception), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.
  10. Subjects must agree not to take live attenuated vaccines (including seasonal flu vaccine) 30 days before randomization, throughout the duration of the trial and for 60 days following the trial.

Exclusion Criteria:

  1. Prior use of fingolimod (Gilenya®).
  2. History or presence of cardiac conditions including:

    1. Cardiovascular or cerebrovascular disease in the previous 6 months (eg. myocardial infarction, unstable angina, or stroke)
    2. Congestive heart failure
    3. First, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances
    4. Any history of Torsades de Pointes
  3. Treatment with a prohibited medication within 30 days of the Baseline Visit:

    a. Class Ia or III antiarrhythmic medications: i.e., Quinidine, Sotalol Includes Nuedexta b. QT interval prolonging medications c. Ketoconazole d. Beta-blockers e. Calcium channel blockers f. Immunosuppressant medication g. Chemotherapeutic (anti-neoplastic) medications

  4. Evidence on examination or ECG of bradycardia (<55 bpm), QTc >450ms for women or >430 msec for men, or 1st degree or higher conduction block.
  5. History of unexplained syncope or cardiac syncope.
  6. Serum AST and ALT value >2.0 times the upper normal limit.
  7. Active infection (acute or chronic).
  8. History of diabetes.
  9. History of macular edema or uveitis.
  10. History of lymphopenia.
  11. History of acquired or inherited immune deficiency syndrome, including leukopenia.
  12. History of severe untreated chronic obstructive sleep apnea.
  13. Exposure to any other agent currently under investigation for the treatment of patients with ALS (off-label use or investigational) within 30 days of the Baseline Visit.
  14. Presence of tracheostomy.
  15. Use of non-invasive ventilation for hypoventilation due to ALS (such as BiPAP).
  16. Presence of feeding tube.
  17. Presence of diaphragmatic pacing system.
  18. The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to PI judgment, or a history of active substance abuse within the prior year.
  19. Clinically significant history of unstable or severe cardiac, oncologic, hepatic, or renal disease, or other medically significant illness.
  20. Pregnant women or women currently breastfeeding.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01786174


Locations
United States, California
University of California, Irvine
Orange, California, United States, 92868
United States, Georgia
Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Texas
Methodist Neurological Institute
Houston, Texas, United States, 77030
Sponsors and Collaborators
Massachusetts General Hospital
ALS Therapy Development Institute
Investigators
Principal Investigator: James D Berry, MD, MPH Massachusetts General Hospital
  More Information

Additional Information:
Responsible Party: James D. Berry MD, MGH Assistant Neurologist, HMS Instructor in Neurology, 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
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by James D. Berry MD, Massachusetts General Hospital:
ALS
Gilenya
Fingolimod

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Fingolimod Hydrochloride
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs