Periodic Reporting for period 3 - TUDCA-ALS (Safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS))
Période du rapport: 2021-01-01 au 2022-06-30
The “Safety and efficacy of tauroursodeoxycholic acid as add-on treatment in patients affected by amyotrophic lateral sclerosis” (TUDCA-ALS) study proposes a novel approach to overcome the current therapeutic impasse. TUDCA-ALS takes advantage of the results of a recent phase IIb study showing that, in patients who received TUDCA in addition to riluzole, the per-year decline rate in the revised-ALS functional rating scale (ALSFRS-R) was about 7 points smaller (on a 0-48 score) compared to riluzole only. This corresponds to a prolongation of median survival by 4-5 months. This strong indication of efficacy is further supported by the evidence that TUDCA has cytoprotective properties in animal models of neurodegenerative diseases.
TUDCA-ALS aims to confirm and further measure the efficacy of TUDCA as a disease-modifier in ALS in a large-scale, phase III, clinical trial. We have assembled a consortium composed of leading European centres with established experience in ALS and a strong catching capability on this patient population. We plan to enrol 440 participants across seven countries in Europe (Italy, Germany, United Kingdom, France, Belgium, Netherlands and Ireland). We have also selected solid biomarkers related to disease progression and cytoprotective activity to test during the treatment period.
In addition to the 7 clinical Consortium Partners, we have selected 18 other centres with relevant expertise in performing clinical trials on ALS. Involved clinical staff has been trained on trial procedures, in order to achieve harmonisation of clinical activities among centres. Regulatory approvals have been obtained in all the 7 countries involved in the project. Ethics approvals have been obtained for all the 25 centres taking part in the trial.
A total of 328 patients has been screened for participation in the study in Italy, Germany, United Kingdom, France, Belgium, Netherlands and Ireland. Following a lead-in period of 3 months, patients meeting the eligibility criteria are randomly assigned to one of two treatment arms (TUDCA or identical placebo, in addition to riluzole) and followed-up for 18 months. Two-hundred forty-nine patients (63% of the target 440 participants) have been randomised to start treatment, while 26 patients are currently in the lead-in period, waiting to be randomised.
Demonstration of TUDCA efficacy in ALS, combined with the validation of new biomarkers of cytoprotection, could be a milestone in developing novel neurodegenerative disease indications for TUDCA. This project implements all the regulatory requirements for obtaining marketing authorisation in case of a positive completion of the study project. This is expected to provide concrete benefits for patients with ALS.
We also intend to valorise the entire dataset for further exploitation of results. Whether the trial produces a positive or negative outcome, the data generated can be used to help improve understanding of the disease natural history and heterogeneity, elucidate the value of candidate biomarkers and help improving future trial design and clinical staging studies.
Overall, TUDCA-ALS will advance science in the field of ALS and more globally of neurodegenerative disorders, contribute to the development of novel therapeutic interventions, strengthen the competitiveness of European research, boost the European innovative capacity and reduce health care costs, ultimately benefiting patients and society as a whole.