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

NCT03293069 | Completed Phase 2 DMC

• 2 other identifiers: 2016_762017-003763-35
• Study Type: interventional
• Target: 372
• Locations: 1 country
• Sites: 15

Brief Summary

The alteration of iron metabolism is reported in animal models of amyotrophic lateral sclerosis (ALS) as well as in sporadic and genetic forms (SOD1 and C9orf72) of ALS. The high iron concentration of the brain, due to its high energy demand (high oxygen consumption), makes motor neurons particularly vulnerable to energy deficit and oxidative stress. Post-mortem examinations and MRI scans in patients with ALS have found signs of iron accumulation in the central motor tract; and a high level of serum ferritin, which is a marker of iron levels, is associated with a lower prognosis. In ALS mouse models, the use of iron chelators has demonstrated neuroprotection and increased life expectancy, suggesting that elimination of excess iron from the brain can prevent neuronal loss and, consequently, a slow progression of the disease. Conservative chelation of iron refers to a modality whereby much of the iron that binds to the chelator is redistributed in the body rather than exhausted. Using a chelator, deferiprone, with this feature, in a safety pilot study, a very good safety profile was observed. Deferiprone eliminated excess iron from brain regions, reduced oxidative damage and cell death associated with regional iron deposits with no apparent negative impact on the iron levels needed. Now, the efficacy of this new therapeutic modality of neuroprotection is being evaluated in a randomized, double-blind, placebo-controlled, multicenter study.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Conservative Iron Chelation; Disease-modifying Strategy

Outcome Measures

Primary Outcomes (1)

• CAFS score (Combined Assessment of Function and Survival)

  CAFS score based on changes in amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) total scores and time to death from baseline (randomization visit) to 12 months

  at 12 months

Secondary Outcomes (10)

• Changes in ALS Functional Rating Scale-Revised (ALSFRS-R) total score

  Baseline, at 12 months

• All-cause and respiratory insufficiency mortality

  at 12 months

• Changes in muscle strength

  Baseline, at 12 months

• Change in the slow vital capacity

  Baseline, at 12 months

• Changes in body weight

  Baseline, at 12 months

Study Arms (2)

Deferiprone

EXPERIMENTAL

Half of participants will receive twice-daily oral deferiprone taken over 12 months.

Drug: Deferiprone

Placebo

PLACEBO COMPARATOR

Half of participants will receive the placebo Twice-daily oral placebo taken over 12 months

Drug: Placebo Oral Tablet

Interventions

Deferiprone DRUG

One 600 mg delayed-release tablets of deferiprone twice a day, for at 30 mg/kg/day

Also known as: DFP

Deferiprone

Placebo Oral Tablet DRUG

the placebo twice daily morning and evening.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 motor deficit 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 sex or 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 do it.) (In case of a limit abnormal value for one of them, it will be recommended that patient 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 sex and
• Able to swallow (required for oral treatment)
• Patients weight included between 40 kg and 130 kg

You may not qualify if:

• Patients with high frequency of comorbidity or vital risks that may reasonably impair life expectancy
• 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 Investigational Medicinal Products (IMPs) and the unknown mechanism by which this agranulocytosis is induced, combining Deferiprone with other medicinal products known to cause agranulocytosis (as described in the IB) will not be allowed. Such medicinal products include clozapine as well as some NSAIDs (e.g. Phenylbutazone or Metamizole), antithyroid agents, sulfonamide antibiotics or methotrexate.
• A history of relapsing neutropenia
• Patients with agranulocytosis or with a history of agranulocytosis.
• Hypersensitivity to Deferiprone
• Pregnant or breastfeeding women or women of childbearing potential not taking highly effective contraception.
• Kidney or liver failure.
• Inability to provide informed consent.
• Patients under trusteeship

Sponsors & Collaborators

• Ministry of Health, France: collaborator
• University Hospital, Lille: lead

Study Sites (15)

Chr Angers

Angers, France

Location

Chru Brest

Brest, France

Location

Hopital Pierre Wertheimer - Hcl - Bron

Bron, France

Location

Chu Cote de Nacre - Caen

Caen, France

Location

Chu de Clermont-Ferrand

Clermont-Ferrand, France

Location

Hôpital Roger Salengro, CHU

Lille, 59000, France

Location

C H U Dupuytren Limoges

Limoges, France

Location

Aphm Hopital La Timone

Marseille, France

Location

Chu de Nancy

Nancy, France

Location

Chu de Nice Hopital Pasteur

Nice, France

Location

Hu Pitie Salpetriere Aphp

Paris, 75013, France

Location

Hopital de Hautepierre

Strasbourg, 67091, France

Location

Chu de Bordeaux - Talence

Talence, France

Location

Chu Toulouse

Toulouse, 31300, France

Location

Chu de Tours

Tours, France

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Deferiprone; Isoflurophate

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organofluorophosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Study Officials

• David Devos, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: September 26, 2017
• Study Start: January 30, 2019
• Primary Completion: November 11, 2023
• Study Completion: May 6, 2024
• Last Updated: December 5, 2025

Record last verified: 2025-12

Locations

FR (15)