Magnet Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting TRICALS Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11]

Trial duration

completed 1 Nov 2025

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Miquel Valls Foundation · MNDA · Fundación Luzón · The Thierry Latran Foundation · Stichting ALS Nederland · Fight MND · Ulla-Carin Lindquist Foundation

External identifiers

EU CT number

2024-516559-41-00

EudraCT number

2020-000579-19

ClinicalTrials.gov

NCT06008249

ISRCTN

ISRCTN15671139

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this study is to assess the efficacy of each drug versus placebo on overall survival, defined as death from any cause or respiratory insufficiency, in patients with ALS.

Secondary objectives 11

1. To assess the effect of each drug versus placebo on a combined assessment of survival and measures of daily functioning (ALS functional rating scale [ALSFRS-R])
2. To assess the effect of each drug versus placebo on ALSFRS-R
3. To assess the effect of each drug versus placebo on respiratory function (SVC)
4. To assess the effect of each drug versus placebo on plasma creatinine
5. To assess the effect of each drug versus placebo on the time to reach advanced disease stages
6. To evaluate the safety and tolerability of each drug administered orally to patients with ALS
7. To assess the effect of each drug versus placebo on change in urinary P75ECD
8. To assess the effect of each drug versus placebo on change in plasma neurofilament light and heavy chain
9. To assess the effect of each drug versus placebo on change in cognitive functioning (ECAS & ALS-FTD-Q)
10. To assess the effect of each drug versus placebo on change in quality of life (EQ-5D)
11. To determine the value of the compound muscle action potential (CMAP) scan to monitor disease progression

Conditions and MedDRA coding

ALS / Amyotrophic Lateral Sclerosis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Age ≥ 18 years at the time of screening.
2. 2. Diagnosis of ALS according to the revised El Escorial criteria (possible, probable-laboratory supported, probable or definite).
3. 3. Capable of providing informed consent and complying with trial procedures, including randomization to sub-studies.
4. 4. TRICALS risk profile ≥ -6.00 and ≤ -2.00 **
5. 5. 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.
6. 6. Women of childbearing potential* must have a negative pregnancy test at baseline and be non-lactating.
7. 7. Men must agree to practice contraception for the duration of the trial and for at least 3 months after last dose of study drug.
8. 8. 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.
9. 9. 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.

Exclusion criteria 17

1. 1. Safety Laboratory Criteria at baseline: o ALT ≥ 5 times upper limit of normal (ULN) o AST ≥ 3 times ULN o Bilirubin ≥ 1.5 times ULN (Gilbert syndrome is accepted) o 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. o Platelet concentration of < 100 x109 per L o Absolute neutrophil count of < 1x109 per L o Haemoglobin < 100 g/L (<6.2 mmol/L) o Both amylase & lipase ≥ 2 times ULN (suspected pancreatitis) o Lactate ≥ 2 times ULN (suspected lactate acidosis)
2. 2. 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.
3. 3. Participation in any other investigational drug trial or using any investigational drug (beginning within 30 days prior to baseline). Only in the exceptional circumstance that an investigational product is available through an EAP, CUP or similar AND for which a clear clinical benefit has been demonstrated in phase 3 study can an exception be made after discussion with the PI and TRICALS.
4. 4. Hypothyroidism unresponsive to thyroid hormone supplementation.
5. 5. Subjects using non-invasive ventilation (NIV, ≥22 h per day) or having a tracheostomy.
6. 6. [No longer applicable since protocol version 3.2]
7. 7. Clinically significant history of unstable or severe cardiac (e.g. congestive heart failure, coronary insufficiency and arrhythmias), oncological, hepatic or renal disease, neuromusculair diseases, significant pulmonary disorder or other medically significant illness.
8. 8. Drug or alcohol abuse.
9. 9. Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit. This exclusion criterion is based on a prior psychiatric diagnosis that is unstable as determined by the subject’s treating Psychiatrist.
10. 10. Presence of frontotemporal dementia which prevents informed consent.
11. 11. Patients heterozygous or homozygous for the A-allele of rs12608932 (UNC13A)
12. 12. Known allergy or hypersensitivity to lithium, or its excipients, or to the components of the placebo.
13. 13. Brain injury with posttraumatic epilepsy or neurologic deficit, excluding a concussion in the medical history. Brain infarction is an exclusion criterion, a transient ischemic attack is not.
14. 14. Addison disease.
15. 15. Patients with the following co-medication: antipsychotics, digoxin and calcium antagonists, carbamazepine, methyldopa, verapamil and diltiazem.
16. 16. Brugada Syndrome or family history of Brugada Syndrome.
17. 17. Plasma sodium <120 mmol/L

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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).

Secondary endpoints 9

1. Composite endpoint evaluating daily functioning and survival based on the joint model framework of survival and longitudinal ALSFRS-R total scores.
2. Daily functioning, defined as mean change from baseline in ALSFRS-R total score.
3. Respiratory function, defined as mean change from baseline in SVC (%predicted of normal according to the GLI-2012 reference standard).
4. Quality of life, defined as change from baseline on the Visual Analogue Scale (single-item scale) and EQ-5D.
5. Neuropsychological status, defined as change from baseline on the ECAS and ALS-FTD-Q.
6. Clinical disease stage, defined as mean time spent in each stage of the King’s and ALS Milano-Torino staging systems.
7. Change from baseline in laboratory parameters: Urinary P75ECD, Neurofilament light and heavy chain, Plasma creatinine
8. Tolerability defined as time-to-discontinuation of assigned treatment since randomization.
9. Safety based on the safety assessments including neurological examinations, clinical laboratory evaluations, vital signs and frequency of adverse events (AEs) or serious adverse events (SAEs). (S)AEs will be categorized according to the Medical Dictionary for Regulatory Activities (MedDRA) and will be rated for severity and association with study drug.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting TRICALS Foundation

Sponsor organisation

Stichting TRICALS Foundation

Address

Goeman Borgesiuslaan 77

City

Utrecht

Postcode

3515 ET

Country

Netherlands

Scientific contact point

Organisation

Stichting TRICALS Foundation

Contact name

Annemarie Janse

Public contact point

Organisation

Stichting TRICALS Foundation

Contact name

Annemarie Janse

Locations

4 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications