Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)

NCT06008249 | Recruiting Phase 3 DMC

• 1 other identifier: MAGNET
• Study Type: interventional
• Target: 171
• Locations: 6 countries
• Sites: 13

Brief Summary

The objective of this phase III, placebo-controlled platform study is to investigate the efficacy of drugs for patients with ALS (Amyotrophic lateral sclerosis).

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Overall survival, defined as time to death from any cause or respiratory insufficiency (DRI; defined as tracheostomy or the use of non-invasive ventilation for ≥22 h per day for ≥10 consecutive days)

  A tracheostomy for ventilation is meant here

  endpoint or 24 months

Secondary Outcomes (11)

• Composite endpoint evaluating daily functioning and survival based on the joint model framework of survival and longitudinal ALSFRS-R total scores

  endpoint or 24 months

• Daily functioning, defined as mean change from baseline in ALSFRS-R total score.

  endpoint or 24 months

• Respiratory function, defined as mean change from baseline in SVC (%predicted of normal according to the GLI-2012 reference standard)

  endpoint or 24 months

• Quality of life, defined as change from baseline on the EQ-5D Visual Analogue Scale (single-item scale)

  endpoint or 24 months

• Quality of life, defined as change from baseline on the EQ-5D

  endpoint or 24 months

Study Arms (2)

Lithium carbonate

EXPERIMENTAL

Lithium carbonate 400 mg capsules will be taken once daily, starting with one capsule (400 mg daily) initially titrated up to two or three capsules daily, depending on blood lithium levels. The target range for the lithium plasma level will be between ≥0.4 mmol/l and ≤ 0.8 mmol/l. Maximum duration is 24 months.

Drug: Lithium Carbonate 400 MG

Placebo

PLACEBO COMPARATOR

Patients start with 1 capsule to be taken once daily, with subsequent sham dose adjustments made to patients on placebo to maintain blinding in clinical sites.

Drug: Lithium Carbonate 400 MG

Interventions

Lithium Carbonate 400 MG DRUG

Lithium carbonate vs placebo (2:1)

Lithium carbonate; Placebo

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years at the time of screening.
• Diagnosis of ALS according to the revised El Escorial criteria (possible, probable-laboratory supported, probable or definite).
• Capable of providing informed consent and complying with trial procedures, including randomization to sub-studies.
• TRICALS risk profile \> -6.0 and \< -2.0 \*\*
• The use of riluzole will be permitted during the study. Subjects taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit.
• Women of childbearing potential\* must have a negative pregnancy test at baseline and be non-lactating.
• Men must agree to practice contraception for the duration of the trial and for at least 3 months after last dose of study drug.
• Men must not plan to father a child or to provide sperm for donation for the duration of the trial and 3 months after the last dose of study drug.
• Women must not be able to become pregnant (e.g. post-menopausal\*\*\*, surgically sterile or using effective birth control methods) for the duration of the study. Effective contraceptives are defined as having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label, including: abstinence, hormonal contraception, intrauterine device in place for ≥ 3 months Appendix 1). Women of childbearing potential must have a negative pregnancy test at baseline, and be non-lactating. Women who are pregnant or are actively seeking to become pregnant, and women of reproductive potential who are not using effective contraceptives are excluded.

You may not qualify if:

• Laboratory Criteria at baseline:
• ALT (alanine transaminase) ≥ 5 times upper limit of normal (ULN)
• AST (aspartate aminotransferase) ≥ 3 times ULN
• Bilirubin ≥ 1.5 times ULN
• Estimated glomerular filtration rate (eGFR) \< 50 mL / min / 1.73 m2 based on Cystatin C, if not available eGFR can also be calculated based on creatinine clearance.
• Platelet concentration of \< 100 x109 per L
• Absolute neutrophil count of \< 1x109 per L
• Haemoglobin \< 100 g/L (\<6.2 mmol/L)
• Amylase \& lipase ≥ 2 times ULN (suspected pancreatitis)
• Lactate ≥ 2 times ULN (suspected lactate acidosis)
• Moderate to severe hepatic impairment according to Child-Pugh classification (Class B or higher; score ≥ 7). Child-Pugh classification is based on bilirubin, albumin, International Normalized Ratio (INR) and presence of encephalopathy or ascites.
• Participation in any other investigational drug trial or using investigational drug (within 30 days prior to screening).
• Hypothyroidism unresponsive to thyroid hormone supplementation.
• Subjects using non-invasive ventilation (NIV, ≥22 h per day) or having a tracheostomy.
• Subjects taking edaravone within 30 days prior to screening. Edaravone is approved by the FDA, but remains an investigational product in Europe and Australia.

Sponsors & Collaborators

• Stichting TRICALS Foundation: lead
• Fight MND: collaborator
• Research Foundation Flanders: collaborator
• MNDA: collaborator
• Thierry Latran Foundation: collaborator
• Ulla-Carin Lindquist Foundation: collaborator
• Luzon Foundation: collaborator
• Alan Davidson Foundation: collaborator
• My name'5 Doddie Foundation: collaborator
• Stichting ALS Nederland: collaborator

Study Sites (13)

Flinders Medical Centre

Adelaide, SA 5042, Australia

NOT YET RECRUITING

Royal Brisbane and Women's Hospital

Brisbane, QLD 4029, Australia

NOT YET RECRUITING

Calvary Health Care Bethlehem

Parkdale, VIC 3195, Australia

NOT YET RECRUITING

Perron Institute

Perth, WA 6009, Australia

NOT YET RECRUITING

The University of Sydney (Royal prince Alfred hospital)

Sydney, NSW 2050, Australia

RECRUITING

Concord hospital Sydney

Sydney, NSW 2139, Australia

NOT YET RECRUITING

University Hospital Leuven

Leuven, 3000, Belgium

RECRUITING

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

RECRUITING

Bellvitge University Hospital

Barcelona, 08907, Spain

RECRUITING

Karolinska University Hospital

Stockholm, 171 64, Sweden

RECRUITING

King's College Hospital

London, SE5 9RS, United Kingdom

RECRUITING

University College London Hospital NHS

London, WC1N 3BG, United Kingdom

NOT YET RECRUITING

University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, ST4 6QG, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Lithium Carbonate

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)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Leonard Van den Berg, MD

  TRICALS Foundation

  STUDY CHAIR

Central Study Contacts

Roel Vink, PhD

CONTACT

+31 6 50177777; magnet@tricals.org

Leonard van den Berg, MD

CONTACT

0887557939; L.H.vandenBerg@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomised in a 2:1 ratio to receive either lithium carbonate or placebo

Study Record Dates

• First Submitted: August 14, 2023
• First Posted: August 23, 2023
• Study Start: August 9, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

ES (1); SE (1); GB (3); AU (6); BE (1); NL (1)