Amyotrophic Lateral Sclerosis (ALS) MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: TUDCABIL
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: tauroursodeoxycholic acid
CAS Number: 14605-22-2
Current Sponsor code: TUDCA
Other descriptive name: TAUROURSODEOXYCHOLIC A
Sponsors
Humanitas Mirasole SpA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria 2. Disease duration = 18 months 3. No swallowing difficulty (4 at ALSFRS-R swallowing subscore) 4. Able to perform reproducible pulmonary function tests 5. Forced vital capacity =70% of normal 6. Stable on riluzole treatment for 3 months in the lead-in period 7. Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 140
Exclusion criteria
Exclusion criteria: 8. Treatment with edaravone or other unaccepted concomitant therapy 9. Other causes of neuromuscular weakness 10. Presence of other neurodegenerative diseases 11. Significant cognitive impairment, clinical dementia or psychiatric illness 12. Severe cardiac or pulmonary disease 13. Other diseases precluding functional assessments 14. Other life-threatening diseases 15. At the time of screening, any use of non-invasive ventilation (e.g. continuous positive airway pres-sure, 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 16. Gastrointestinal disorder that is likely to impair absorption of study drug from the gastrointestinal tract 17. Has taken any investigational study drug within 30 days or five halflives of the prior agent, whichever is longer, prior to dosing 18. Any clinically significant laboratory abnormality 19. Other concurrent investigational medications 20. Active peptic ulcer 21. Previous surgery or infections of small intestine 22. Patients unable to easily swallow the treatment pills at time of enrolment 23. Occurrence of frequent biliary colic, biliary infections, severe pancreatic abnormalities 24. Subjects who weigh 88 lbs (40 kg) or less at screening 25. Aspartate aminotransferase or alanine aminotransferase concentrations more than 3 times the upper limit of normal 26. Creatinine clearance 50 ml/min or less 27. Any clinically significant neurological, haematological, autoimmune, endocrine, cardiovascular, neo-plastic, 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 interpre-tation of study results 28. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to re-ceive TUDCA or that the subject is unable or unlikely to comply with the dosing schedule or study evaluations 29. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To asses the efficacy of TUDCA in slowing disease prograssion in patients with ALS during the treatment period compared to the lead-in phase as measured by ALSFRS-R;Secondary Objective: - To assess the efficacy of TUDCA in slowing disease progression and functional impairment in patients with ALS, as measured by the survival time, the ALSAQ-40 questionnaire, FVC, the EQ-5D, and muscle force - To assess the long term safety and tolerability of TUDCA for up to 18 months in patients with ALS. The exploratory objectives of this study are: - To evaluate the effect of TUDCA on possible biomarkers: CSF and serum neurofilament levels, serum MMP-9 expression, and plasma creatinine levels.;Primary end point(s): Primary endpoint is measured through identification of the responder patients defined as those showing an improvement of at least 20% in the ALSFRS-R slope during the 18 months compared to the lead-in period. For each randomised patient, slope coefficients of ALSFRS-R are calculated by linear regression models sep-arately during the lead-in period and during the 18 months of treatment period;Timepoint(s) of evaluation of this end point: This endpoint will be evaluate during the initial observation period and during the 18 months of the treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Survival time measured by death or respiratory insufficiency (DRI; defined as tracheostomy or the use of non-invasive ventilation for =22 h per day for =10 consecutive days). • Difference in change from baseline in disease progression and functional impairment between TUDCA and placebo over 18 months (as measured by ALSFRS-R, ALSAQ-40 questionnaire, Forced Vital Capacity , EQ-5D scale and MRC sum-score). • Long-term safety and tolerability of TUDCA treatment in patients with ALS for up to 18 months (as assessed through adverse reaction, concomitant treatment, physical examination, vital signs and routine haematology and biochemistry analyses). • Effect of TUDCA on biomarkers of disease progression (such as CSF and serum Neurofilament levels, serum MMP-9 expression and plasma creatinine levels) over 18 months in comparison to placebo.;Timepoint(s) of evaluation of this end point: All efficacy and safety endpoints will be compared between the two randomization groups at the end of the study | — |
Countries
Belgium, France, Germany, Italy, Netherlands, United Kingdom
Contacts
Public ContactUfficio Sperimentazioni Cliniche
Istituto Clinico Humanitas
Outcome results
None listed