Gilenya in Amyotrophic Lateral Sclerosis (ALS)
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Gilenya; Placebo
Intervention description: 0.5mg Gilenya orally by mouth once daily for approximately 28 days; 0.5mg placebo (sugar pill) orally by mouth once daily for approximately 28 days
Intervention MeSH terms: Fingolimod Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ALS; Gilenya; Fingolimod

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).
    

Eligibility 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.