Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS

This is a Phase III, multi-centre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS).

Enrolled patients will be randomized to one of two treatment arms: TUDCA or identical placebo by oral route. The randomization will be performed in a ratio one to one for the two arms.

TUDCA will be administered orally at the dose of 1 g twice daily (2 g daily) for 18 months. Patients will be taking also riluzole at the dose of 50 mg twice daily (100 mg daily).

Patient randomization will take place after a screening (lead-in) period of 12 weeks (3 months) with 3 assessments at 6-week intervals. Clinical assessments during the trial phase will be performed every three months. This will allow measuring the progression rate before and after starting treatment (either active or placebo).

Eligibility Criteria:
Inclusion Criteria:

* Probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria at screening visit (month -3)
* Disease duration ≤ 18 months at screening visit (month -3)
* Able to perform reproducible pulmonary function tests at screening visit (month -3)
* Forced vital capacity or slow vital capacity ≥70% of normal at screening visit (month -3)
* Stable on riluzole treatment for 3 months in the lead-in period
* Signed informed consent at screening visit (month -3)

Exclusion Criteria:

* Treatment with edaravone
* Other causes of neuromuscular weakness
* Presence of other neurodegenerative diseases
* Significant cognitive impairment, clinical dementia or psychiatric illness
* Severe cardiac or pulmonary disease
* Other diseases precluding functional assessments
* Other life-threatening diseases
* Any use of non-invasive ventilation (e.g. continuous positive airway pressure, non-invasive bi-level positive airway pressure or non-invasive volume ventilation) for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
* Gastrointestinal disorder that is likely to impair absorption of study drug from the gastrointestinal tract
* Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is longer, prior to dosing
* Any clinically significant laboratory abnormality
* Other concurrent investigational medications
* Active peptic ulcer
* Previous surgery or infections of small intestine
* Patients unable to easily swallow the treatment pills
* Acute inflammation of the gallbladder or bile ducts
* Occurrence of frequent biliary colic, biliary infections, severe pancreatic abnormalities
* Bile duct obstruction, calcified X-ray opaque gallstones and reduced mobility of the gallbladder
* Subjects who weigh 88 lbs (40 kg) or less
* Aspartate aminotransferase or alanine aminotransferase concentrations more than 3 times the upper limit of normal
* Creatinine clearance 50 ml/min or less
* Any clinically significant neurological, haematological, autoimmune, endocrine, cardiovascular, neoplastic, renal, gastrointestinal, or other disorder that, in the Investigator's opinion, could interfere with the subject's participation in the study, place the subject at increased risk, or confound interpretation of study results
* Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive TUDCA or that the subject is unable or unlikely to comply with the dosing schedule or study evaluations
* The patient of reproductive potential is sexually active and is not willing to use highly effective contraception during the study and up to 90 days after the day of last dose
* The patient is pregnant or breast feeding