Gilenya in Amyotrophic Lateral Sclerosis (ALS)

NCT01786174 | Completed Phase 2 Results DMC

• 1 other identifier: 2013P000313
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

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).

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Gilenya; Fingolimod

Outcome Measures

Primary Outcomes (3)

• ALSFRS-R Total Score at Weeks 0, 2, 4 and 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.

  Week 0, Week 2, Week 4 and Week 8

• Change in Slow Vital Capacity Score (SVC)

  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.

  Week 0, Week 2, Week 4 and Week 8

• Forced Expiratory Volume in 1 Second (FEV1)

  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.

  Screening, Week 0, Week 2, and Week 4

Secondary Outcomes (2)

• Lymphocyte (T-Cell) Subset Trajectories

  Week 0, Week 2, and Week 4

• Forced Expiratory Volume in 1 Second (FEV1) / Slow Vital Capacity (SVC) Ratio

  Screening, Week 0, Week 2, and Week 4

Study Arms (2)

Gilenya (fingolimod)

EXPERIMENTAL

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

Drug: Gilenya

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Gilenya DRUG

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

Also known as: fingolimod

Gilenya (fingolimod)

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
• Onset of weakness or spasticity due to ALS ≤ 2 years (24 months) prior to Baseline Visit.
• Slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and age at the screening visit.
• 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).
• 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.
• Capable of providing informed consent and following trial procedures.
• Geographically accessible to the site.
• 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.
• 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.

You may not qualify if:

• Prior use of fingolimod (Gilenya®).
• History or presence of cardiac conditions including:
• Cardiovascular or cerebrovascular disease in the previous 6 months (eg. myocardial infarction, unstable angina, or stroke)
• Congestive heart failure
• First, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances
• Any history of Torsades de Pointes
• 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
• 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.
• History of unexplained syncope or cardiac syncope.
• Serum AST and ALT value \>2.0 times the upper normal limit.
• Active infection (acute or chronic).
• History of diabetes.
• History of macular edema or uveitis.
• History of lymphopenia.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• ALS Therapy Development Institute: collaborator

Study Sites (4)

University of California, Irvine

Orange, California, 92868, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

Related Links

• ALS Therapy Development Institute (ALS TDI)
• Northeast ALS Consortium (NEALS)

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Fingolimod Hydrochloride

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sphingosine; Amino Alcohols; Alcohols; Organic Chemicals; Propylene Glycols; Glycols; Amines

Results Point of Contact

• Title: James D. Berry, MD, MPH
• Organization: Massachusetts General Hospital

jdberry@mgh.harvard.edu

617-726-5097

Study Officials

• James D Berry, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MGH Assistant Neurologist, HMS Instructor in Neurology

Study Record Dates

• First Submitted: February 4, 2013
• First Posted: February 7, 2013
• Study Start: August 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: May 1, 2015
• Last Updated: July 1, 2016
• Results First Posted: December 31, 2015

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)