PREVAiLS: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Pridopidine in Participants with ALS

Topic:

Clinical Trials

Poster Number: 428 O

Author(s):

Sabrina Paganoni, MD, PhD, Spaulding Rehabilitation Hospital, Angela Genge, MD, McGill University, Melanie L. Leitner, PhD, Accelerating NeuroVentures, Bernd-Jan Sanson, MD, PhD, Prilenia Therapeutics, Ryan Miller, MD, Prilenia Therapeutics, Nils Confer, PhD, MBA, Prilenia, Wei Feng, Prilenia Therapeutics, Diderik Boot, PhD, Prilenia Therapeutics, Michael R. Hayden, MB, ChB, PhD, FRCP(C), FRSC, Prilenia Therapeutics; Center for Molecular Medicine and Therapeutics University of British Columbia, Leonard H. van den Berg, MD, PhD, UMC Utrecht

Background: Pridopidine is a selective Sigma-1 receptor (S1R) agonist in clinical development. Compelling evidence demonstrates its neuroprotective properties in preclinical models of ALS.
Pridopidine 45 mg given orally twice daily (bid) was evaluated in the HEALEY ALS Platform Trial. In a subgroup of more rapidly progressing participants, meeting definite or probable ALS by El Escorial Criteria (EEC) and <18 months from symptom onset, pridopidine showed improvement vs placebo in ALSFRS-R Total (p=0.03), Respiratory (p=0.03) and Bulbar (p=0.06) subdomains at 24 weeks. Pridopidine demonstrated significant benefits in quantitative speech measures, specifically in speaking (p<0.01) and articulation (p<0.01) rates. Within this subgroup, the time to 50% probability of survival was substantially prolonged (from 300 to 600 days, log rank test p=0.069). All p-values are nominal. Pridopidine’s safety profile was comparable to placebo. These data informed the design of PREVAiLS, a global phase 3 trial which will further evaluate pridopidine’s effects in this population. Objective: To evaluate the safety and efficacy of pridopidine in people with early rapidly progressing ALS. PREVAiLS Study design: Eligibility criteria includes people aged 18-80 with definite or probable ALS, <18 months from disease onset. Participants will be randomized 3:2 to either active (45 mg bid) or placebo arm with standard of care (including riluzole, edaravone and Nuedexta®). The 48-week double-blind period will be followed by a 48-week open-label extension. Primary endpoint is change from baseline in ALSFRS-R adjusted for mortality at 48 weeks. Secondary endpoints include effects of pridopidine on survival, quantitative measures of speech, respiratory and bulbar function, and quality of life. Patient-reported outcomes assessing communication and blood biomarkers will also be evaluated. Conclusion: The HEALEY ALS Platform trial demonstrated a potential benefit of pridopidine on ALS progression in a subgroup of rapidly progressing patients early in their disease. PREVAiLS will further evaluate pridopidine in this population.