ACETYLCARNITINE HYDROCHLORIDE for Amyotrophic lateral sclerosis

Inclusion criteria

• {"criterion_text":"- Age 18+;\n- Intact cognitive function, again determined by the Principal Investigator.\n- ALS diagnosis according to the Gold Coast Criteria\n- Disease duration ≤ 24 months from symptom onset, as indicated by limb weakness or bulbar symptoms, at the randomization/baseline visit\n- Self-sufficiency [Satisfactory bulbar and spinal function (score 3+ on the ALSFRS-R for swallowing, cutting food and handling utensils, and walking)];\n- Satisfactory respiratory function (FVC ≥80% of predicted);\n- Documented progression of symptoms as measured by the ALSFRS-R scale. Disease progression rate (DFS) must be>= 0.33. DFS =(48- ALSFRS-R at screening)/months from onset to screening;\n- Ability to understand and comply with the study requirements;\n- Ability to give written informed consent personally or, as an alternative, via a legally authorized representative;\n- Treatment with riluzole 50 mg twice/day for at least 4 weeks prior to randomization visit;"}

Exclusion criteria

• {"criterion_text":"- Antecedent polio infection or other active infection;\n- Motor neuron disease (MND) other than ALS;\n- Involvement of other systems possibly determining a functional impairment (as measured by the endpoints) for the entire duration of the study;\n- Other severe clinical conditions (e.g., cardiovascular disorders, neoplasms) with an impact on survival or functional disability in the next 12 months;\n- Previous use of ALCAR for any reason;\n- Poor compliance with previous treatments;\n- Other experimental treatments in the three months prior to the screening visit (if a subject is receiving another experimental drug, a 3-month wash-out period before participating in the present clinical trial will be required);\n- Women who are lactating or able to become pregnant (e.g. who are not post-menopausal, surgically sterile, or using inadequate birth control) and men unable to practice contraception for the duration of the treatment and three months after its completion;\n- Inability to understand and comply with the study requirements;\n- Unwillingness or inability to take riluzole."}

Primary endpoints

• {"endpoint_text":"- The proportion of participants remaining self-sufficient after 48 weeks in each treatment arm (those scoring three or higher in all the three ALSFRS-R items for swallowing, cutting food, handling utensils, and walking).","definition_or_measurement_approach":"Proportion of participants who remain self-sufficient at week 48, defined as scoring three or higher in each of the three specified ALSFRS-R items (swallowing, cutting food and handling utensils, and walking); measured using the ALSFRS-R at baseline and at week 48."}

Secondary endpoints

• {"endpoint_text":"- Mean change of ALSFRS-R total score in each treatment arm from baseline to week 48.\n- Mean change of FVC% in each treatment arm from baseline to week 48.\n- Mean change in the five domains of ALSAQ-40 measuring different aspects of quality of life (physical mobility, ADL/independence, eating and drinking, emotional reactions, communication) in each treatment arm from baseline to week 48.\n- Mean change in ECAS total score in each treatment arm from baseline to week 48.\n- Cumulative probability of remaining self-sufficient in each treatment arm during 48 weeks.\n- Cumulative probability of remaining free from a 6-point or greater decline in ALSFRS-R total score in each treatment arm during 48 weeks.\n- Cumulative probability of remaining without gastrostomy in each treatment arm during 48 weeks.\n- Cumulative probability of remaining without non-invasive ventilation (NIV) support (≥12 hours a day in a 24-hour period) in each treatment arm during 48 weeks.\n- Cumulative survival probability (of being alive and without tracheostomy) in each treatment arm during 48 weeks\n- The mean change in the levels of PGC-1 alpha, 3-NT, acetyl-PPIA in the peripheral blood mononuclear cells (PBMCs) and of NFL, MMP-9, MCP-1, CK, MiR-206, Musclin/osteocrin, Uric acid, HNE in plasma in each treatment arm, during the entire treatment period (from baseline to 48 weeks).\n- Number of adverse events and serious adverse events in each treatment arm during 48 weeks of treatment.","definition_or_measurement_approach":"Mean change endpoints: difference between baseline and week 48 values (ALSFRS-R total, FVC%, ALSAQ-40 domains, ECAS total). Cumulative probability endpoints: time-to-event analyses over 48 weeks (remaining self-sufficient, free from ≥6-point ALSFRS-R decline, without gastrostomy, without NIV ≥12h/day, survival without tracheostomy). Biomarker endpoints: mean change from baseline to week 48 in listed PBMC and plasma biomarkers. Safety: count and categorisation of adverse events and serious adverse events over 48 weeks."}

Italy

Earliest CTIS Part Ii Submission Date

15-10-2024

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

533

Number Of Sites

20

Number Of Participants

236

Primary sponsor

Full Name

Istituto Di Ricerche Farmacologiche Mario Negri

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Italy