Conservative Iron Chelation as a Disease-modifying Strategy in Amyotrophic Lateral Sclerosis

Inclusion Criteria:

• Categorized as; possible, laboratory supported probable, probable, or definite ALS (revised El Escorial criteria)

• Spinal and bulbar forms of ALS

• Duration of the disease of less than 18 months since the first symptoms of motordeficit or amyotrophy (isolated cramps or fasciculation will not be considered).

• Duration of the disease of less than 6 months since the diagnosis

• An upright slow vital capacity ≥ 75% of the predicted value for age, height, and sexor at least one test on inspiratory pressure ≥ 60% of the predicted value for age,height, and sex which could be either maximal inspiratory pressure or a SNIFF test. (The best predictive test is sniff test but sometime patients are not able to doit.) (In case of a limit abnormal value for one of them, it will be recommended thatpatient re-assessment occurs three months later).

• A mild functional handicap score for ALSFRS-R ≥36

• An upright slow vital capacity > 70% of the predicted value for age, height, and sexand

• Able to swallow (required for oral treatment)

• Patients weight included between 40 kg and 130 kg

• If the patient is under riluzole, it has to be for at least 1 month before inclusionwith stable dose (to rule out the principal risk of hepatitis)

Exclusion Criteria:

• Patients with high frequency of comorbidity or vital risks that may reasonablyimpair life expectancy

• Progressing axis I psychiatric disorders (psychosis, hallucinations, substanceaddiction, bipolar disorder, severe depression, suicidal ideation), in accordancewith the Diagnostic and Statistical Manual of Mental Disorders. Before entry intothe study, exclusion or stabilization of conditions must occur for patientssuffering from mild or moderate depressive episodes (not in remission) or severe anduncontrolled anxiety.

• Dementia according to the Diagnostic and Statistical Manual of Mental Disorders

• Exposure to any other experimental drug up to 30 days before day 1

• Due to the risk of agranulocytosis (estimated at 2%) caused by the InvestigationalMedicinal Products (IMPs) and the unknown mechanism by which this agranulocytosis isinduced, combining Deferiprone with other medicinal products known to causeagranulocytosis (as described in the IB) will not be allowed. Such medicinalproducts include clozapine as well as some NSAIDs (e.g. Phenylbutazone orMetamizole), antithyroid agents, sulfonamide antibiotics or methotrexate.

• A history of relapsing neutropenia

• Patients with agranulocytosis or with a history of agranulocytosis.

• Hypersensitivity to Deferiprone

• Patients with anaemia (regardless of latter aetiology) or a history of anotherhaematological disease. Haemochromatosis is not an exclusion criterion ifcontrolled.

• Pregnant or breastfeeding women or women of childbearing potential not taking highlyeffective contraception.

• Kidney or liver failure.

• Inability to provide informed consent.

• Participation in another clinical trial within 1 month prior to inclusion in thestudy

• Patients under trusteeship