Safety of Intrathecal Riluzole in Patients With Amyotrophic Lateral Sclerosis

Prior treatment

• History of active substance abuse within the prior year.
• Exposure to any investigational drug, device, or biologic within 30 days of screening.

Other illness

• Presence of infection including but not limited to: meningitis, ventriculitis, skin infection, bacteremia, or septicemia.
• Testing positive for HIV (anti-HIV antibody), HBV (HBV surface antigen) or HCV (anti-HCV antibody; HCV RNA if anti-HCV antibody is positive) at screening.
• The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair the ability of the participant to provide informed consent, per investigator judgment.
• Clinically significant history of unstable or severe cardiac, oncologic, hepatic, or renal disease, or other medically significant illness.

Lab values

• Participants at risk of increased bleeding or uncontrolled bleeding during the SynchroMed II Infusion Pump implantation or following explant. This includes but is not limited to:
  • Anatomical factors at or near the site of implantation;
  • Underlying disorders of the coagulation cascade or platelet function (eg, hemophilia, Von Willebrand's disease, liver disease);
  • Administration of antiplatelet or anticoagulant medication within 7 days before or after pump implantation (eg, aspirin, clopidogrel bisulfate, rivaroxaban, nonsteroidal anti-inflammatory agents \[NSAIDs\]), or
  • Use of nutritional supplements (eg, St John's Wort) within 7 days before or after pump implantation.
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) value \> 2.0 times the upper normal.

Other

• Participants with bulbar-onset ALS
• Inability to have the infusion pump implanted ≤ 2.5 cm below the skin surface.
• Body weight and size unable to accept the infusion pump bulk and weight.
• Spinal anomalies which would complicate the implantation and fixation of the catheter for IP delivery.
• A life expectancy of less than 6 months, based on the judgment of the investigator.
• Presence of tracheostomy.
• At risk for committing suicide per investigator judgment.
• Pregnant women or women currently breastfeeding.

• Men and women aged 18 years or older.
• Participants are ambulatory with or without an assistive device.
• Sporadic or familial ALS diagnosis with possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
• Slow vital capacity (SVC) measure ≥70% of predicted for gender, height, and age.
• Medically able to undergo implantation of the SynchroMed II Infusion Pump according to the judgment of the investigator, or the presence of a previously implanted IT pump (not to be used for concurrent IT infusion of another IT agent).
• Capable of reading and providing informed consent and following study procedures.
• Geographic accessibility to the study center and the ability to travel to the clinic for study visits by ground transportation.
• Women must not be able to become pregnant (eg, post menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and 3 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 in place for ≥3 months, barrier method in conjunction with spermicide, or another adequate method.
• Taking and tolerating oral riluzole 50 mg twice a day for at least 30 days prior screening and willingness to continue oral riluzole throughout duration of the study.
• Patients may take other drugs approved for treatment of ALS at the dose prescribed by their neurologist.