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

• Status: Recruiting
• Trial end date: 2022-12-30
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Humanitas Mirasole SpA
• Collaborators: Bruschettini S.r.l.; European Commission; Istituto Superiore di Sanità; KU Leuven; Motor Neurone Disease Association; UMC Utrecht; University Hospital, Tours; University of Dublin, Trinity College; University of Sheffield; University of Ulm
• Treatments: Taurochenodeoxycholic Acid; Tauroursodeoxycholic acid; Ursodoxicoltaurine

Criteria

Inclusion Criteria:

• Probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria 34

• Disease duration ≤ 18 months

• No swallowing difficulty (4 at ALSFRS-R swallowing subscore)

• Able to perform reproducible pulmonary function tests

• Forced vital capacity ≥70% of normal

• Stable on riluzole treatment for 3 months in the lead-in period

• Able to perform reproducible pulmonary function tests

• Signed informed consent

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

• At the time of screening, 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 at time of enrolment

• Occurrence of frequent biliary colic, biliary infections, severe pancreatic abnormalities

• Subjects who weigh 88 lbs (40 kg) or less at screening

• Aspartate aminotransferase or alanine aminotransferase concentrations more than 3 times the upper limit of normal

• Creatinine clearance 50 ml/min or less

• Previous exposure to bile acids

• 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 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