Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition, mainly characterized by progressive weakness and wasting of the limbs, the respiratory and bulbar muscles. Respiratory insufficiency leads to a fatal outcome after a mean diseases duration of only three to five years. The disease is characterized by pathological accumulations of a protein called TDP-43, which can be found large cortical and sub-cortical areas of post-mortem ALS brains. No causal treatment for this condition is known to date, and there is a large unmet need to develop new strategies in order to halt or slow down its progression. The aim of this study is to test the safety and tolerability of Tideglusib, a treatment that is already in clinical trials for other neuromuscular conditions, in patients with ALS. It is assumed that this drug may have a significant therapeutic benefit in this population due to his mode of action: In the ALS mouse model, Tideglusib decreases significantly the amount of accumulated TDP-43 proteins within the cells.

Official Title
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Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis (TIDALS): a Randomized Placebo-controlled Phase II Trial

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Tideglusib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Possible, probable (clinically or laboratory supported) or definite ALS according to the revised version of the El Escorial criteria Disease duration < 18 months Vital capacity of more than 60% of normal (defined as slow vital capacity, best of three measurements) Age more than 18 years On a stable dose of riluzole for at least four weeks or not taking riluzole On a stable dose of edaravone for at least four weeks or not taking edaravone Capable of thoroughly understanding all information given and giving full informed consent according to GCP Exclusion Criteria: Previous participation in another clinical study within the preceding 12 weeks Proven SOD1- or FUS - mutation Tracheostomy or assisted ventilation of any type during the preceding three months Pregnancy or breast-feeding females Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment Evidence of a major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms Alcoholism Cardiovascular disorder/arrhythmia Impaired kidney function, defined as creatinine levels of 2.5 x upper limit of normal (ULN) Impaired liver function, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) of 3 x ULN Liable to be not cooperative or comply with trial requirements as assessed by the investigator, or unable to be reached in the case of emergency

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tideglusib<br>Patients receive 1000 mg Tideglusib once daily per os | Drug: Tideglusib<br>* 1000 mg/day per os<br>|
| Placebo Comparator: Placebo<br>Patients receive placebo matching Tideglusib 100 mg once daily per os | Drug: Tideglusib<br>* 1000 mg/day per os<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in Alanine Aminotransferase | Increase in Alanine Aminotransferase < 3x of Upper Limit of Normal | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Most common side effect | Occurence of diarrhea in less then 18 % of patients | 14 weeks |