RILUZOLE for Spasticity | Spinal cord injury

Inclusion criteria

• {"criterion_text":"- Chronic traumatic SCI defined as: a. At least a 12-month history of i. C4-T12 traumatic SCI ii. Complete and incomplete ( AIS A,B,C,D) iii. With Spasticity (5>MAS>1 on at least adductor muscles and/or triceps surae muscles and NRS ≥ 4)\n- itten informed consent provided by subject\n- Male or Female\n- Aged 18 to 65 years at the time of screening\n- Judged by site investigator to be able to comply with evaluations at baseline and throughout the study\n- Last injection of BTX-A in striated muscle more than 3 months ago and patients must have returned to their level of spasticity before BTX-A injection\n- Last intrathecal (IT) injection of baclofen or per os administration of any myorelaxant should be more than 14 days ago (Step 1)\n- The dose of myorelaxant or Baclofen should be stable for ≥ 30 days prior to screening and kept at stable daily dose until the end of the protocol (Step 2).\n- Stable on all other chronic medications for ≥ 30 days prior to screening, including analgesics\n- Stable on rehabilitation (methods and frequency) for ≥ 15 days prior to screening"}

Exclusion criteria

• {"criterion_text":"- Spinal cord injury of less than 12 months,\n- Neutropenia, liver enzymes (ALT/SGPT or AST/SGOT) 2 times the upper limit of normal (ULN) at screening visit, baseline elevations of several liver function tests (especially elevated bilirubin).\n- AIDS or AIDS-related complex,\n- The systolic blood pressure measurement is > 190 or < 85 mm Hg and/or the diastolic blood pressure measurement is > 105 or < 50 mm Hg at screening.\n- The ECG is abnormal at screening and judged to be clinically significant by the site investigator. Particular attention will be given to any sign suggesting conduction disorders.\n- Treatment with any investigational drugs or device within 60 days of screening\n- Any myorelaxant medication including IT baclofen, taken by the subject in the last 14 days prior to screening (step 1)\n- Not stable under IT baclofen or per os myorelaxant medication for at least 30 days prior screening (step 2)\n- Not stable on all other chronic medications for ≥ 30 days prior to screening, including analgesics\n- injection of BTX-A in striated muscle less than 3 months ago\n- Subject is currently using, and will continue to use for the next 14 days any of the following medications which are classified as Inhibitors of CYP 1A2 (e.g. diclofenac, diazepam, nicergoline, clomipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline and quinolones) or Inducers of CYP 1A2 (e.g. rifampicin and omeprazole)\n- Associated Brain lesion that might be the cause of spasticity,\n- Ongoing pregnancy and women with childbearing potential not using any form of efficacious contraception during study and 3 months after the end of study.\n- Ongoing lactation and during 3 months after the end of study.\n- known hypersensitivity to Riluzole\n- MAS≤1 or =5on at least adductor muscles and/or triceps surae muscles or NRS < 4\n- Presence of urinary infection, fever, pressure ulcer or other spasticity-aggravating factors.\n- Presence of other significant neurological or mental disorder or other illness, which would preclude accurate evaluation,\n- Recent history (less than 1 year) of chemical substance dependency or significant psychosocial disturbance,\n- Insufficient fluency in local language to complete neuropsychological, global and spasticity assessments\n- Active liver disease or clinical jaundice\n- Active malignancy"}

Primary endpoints

• {"endpoint_text":"- the improvement of Modified Ashworth Score better than 1 point, or 11 points Numerical Rating Scale (0-10 NRS) spasticity score better than 20% between Week 0 and Week 2.","definition_or_measurement_approach":"Binary success/failure: success defined as improvement of 1 point on the Modified Ashworth Scale (MAS) OR improvement of 20% between Day 1 and Day 14 on the 0-10 Numerical Rating Scale (NRS) for spasticity."}

Secondary endpoints

• {"endpoint_text":"- Safety : side effects","definition_or_measurement_approach":"Safety assessed by recording adverse events/side effects."}
• {"endpoint_text":"- Pharmacokinetics (PK): Blood sampling time points will be estimated using Limited Sampling Strategy (according to the selected galenic form and sex). Individual PK parameters will be calculated using standard compartimental approaches. In particular, exposure parameters (i.e., Cmax, Ctrough, AUC) will be evaluated.","definition_or_measurement_approach":"PK: plasma concentrations measured (HPLC noted in translation) at specified time points (T0 predose and T2h post-dose at visits) with individual PK parameters (Cmax, Ctrough, AUC) calculated using compartmental models."}
• {"endpoint_text":"- Electrophysiology: H reflex, mean F wave amplitude, surface EMG at T0 (before drug intake) at T2h (2h after drug intake) (only in Step 2)","definition_or_measurement_approach":"Electrophysiology measures (H reflex, mean F wave amplitude, surface EMG) recorded at baseline (T0) and 2 hours post-dose (T2h) (only in Step 2)."}
• {"endpoint_text":"- Efficacy : 0-10 NRS score, Modified Ashworth score (MAS) on at least adductor muscles and/or triceps surae, Patient Global Impression of Change, Penn Spasm frequency scale","definition_or_measurement_approach":"Efficacy assessed using 0-10 NRS for spasticity, Modified Ashworth Scale on specified muscles, PGIC (7-point scale), and Penn Spasm Frequency Scale."}
• {"endpoint_text":"- Pain : Visual Analog Scales, Neuropathic Pain Symptom Inventory, International Spinal Cord Injury Basic Data Set (ISCIPDS)","definition_or_measurement_approach":"Pain assessed via Visual Analog Scales (VAS), Neuropathic Pain Symptom Inventory (NPSI), and ISCIPDS instruments."}
• {"endpoint_text":"- Activities and Participation: Spinal Cord Injury Independence Measure (SCIM scale) (only in Step 2); Personal therapeutic objectives determined at baseline, Goal Attainment Scale (GAS) (Adductor muscle spasticity...)","definition_or_measurement_approach":"Activities and participation measured using SCIM (only Step 2), baseline personal therapeutic objectives and Goal Attainment Scale (GAS)."}
• {"endpoint_text":"- Bladder dysfunction: Bladder diary (items on urinary frequency, daytime incontinence...) (Only in Step 2)","definition_or_measurement_approach":"Bladder dysfunction assessed via bladder diary documenting frequency and incontinence during specified pre-visit periods (3 days before Visit 2 and Visit 4)."}

France

Earliest CTIS Part Ii Submission Date

03-07-2024

Latest Decision Or Authorization Date

31-07-2024

Processing Time Days

28

Number Of Sites

3

Number Of Participants

90

Primary sponsor

Full Name

Centre Hospitalier Regional De Marseille

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"DGOS _PHRCN","duties_or_roles":"Source of monetary support","organisation_type":""}