Effectiveness and safety of riluzole for the treatment of seizures in individuals with SCN8A developmental and epileptic encephalopathy (SCN8A-DEE).

Riluzole suspension. Oral, Percutaneous Endoscopic Gastrostomy (PEG) or Nasogastric Tube (NGT), The Austin Clinical Trials Pharmacy will prepare and dispense the study medications (riluzole suspension and matching placebo). During the open-label dose exploration phase, the study medication (riluzole or placebo) will be dispensed at each study visit. During the multi-crossover randomised-controlled trial (MC RCT), the study medication will be dispensed in the first visit of each treatment period. Participants will be requested to bring unused study medication to the clinic at each visit. Study personal will count the suspension volume at study visits to check accountability. All dosages prescribed and administered to the participant and all dose changes during the study must be recorded on the Dosage Administration Record case report form (CRF). A medication information sheet will be provided to the participants detailing instructions for administration. Participants will enter an initial open-label dose-exploration phase, to inform on doses that are tolerated and appear to be effective for that individual. If there is a significant improvement (as determined by the N-of-1 Steering Committee), the participant will be invited to enter the MC RCT, comprising 2 crossovers of riluzole and placebo treatment period (a total of 4 treatment periods). For participants without a signal of significant improvement at the highest tolerated (or permitted) dose, the study is terminate at the conclusion of the open-label dose-exploration phase. The pre-determined maximal permitted dose is 60mg/m2/day up to 100mg/day. The maximally tolerated dose is determined by review of dose-limiting toxicities. Phase 1 - open-label dose-exploration phase: 1. Up-titration: Week 1: - Children (<16 yo) 30 mg/m2 (up to 50 mg/day) - Adults 50mg/day Week 2: - Children (<16 yo) 60 mg/m2 (up to 100 mg/day) - Adults 100mg/day Week 3: - Children (<16 yo) 90mg/m2 (up to 150mg/day - Adults 150mg/day 2. Maintenance: 4 weeks at the maximally tolerated dose reached during the up-titration period, staying at same dose of up to: - Children (<16 yo) 120 mg/m2 (up to 200mg/day) - Adults 200mg/day 3. Down-titration: 3 days at 50% of the maintenance dose Phase 2 - multi-crossover randomised controlled trial (MC RCT), comprising 4 randomised treatment periods (2 riluzole and 2 placebo). Each period is 6 weeks and 3 days, comprising: 1. Up-titration: - 1 week at 50% of the target dose established during the open-label dose exploration phase 2. Maintenance: - 4 weeks at 100% of the target dose 3. Down-titration: 3 days at 50% of the target dose 4. Wash-out 7 days of no investigational treatment