Clinical trial: Gilenya in Amyotrophic Lateral Sclerosis (ALS) (NCT01786174)

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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient description (patient's own words): I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Does the patient match the trial criteria? 1