Amyotrophic Lateral Sclerosis
Conditions
Brief summary
The goal of this clinical trial is to learn if the drug pridopidine works to treat amyotrophic lateral sclerosis in adults. It will also help to learn about the safety of pridopidine. The main question it aims to answer is: Does pridopidine slow disease progression of ALS? Researchers will compare pridopidine to a placebo (a look-alike substance that contains no drug) to see if pridopidine works to treat ALS. Participants will: Take pridopidine or a placebo by mouth every day for 48 weeks. Afterwards, all participants will take pridopidine for another 48 weeks. Visit the clinic once every 1-3 months for checkups and tests
Detailed description
This is a Phase 3, randomized study consisting of a double-blind placebo-controlled (DBPC) period followed by an open-label extension (OLE) to evaluate the efficacy and safety of pridopidine administered orally at a dose of 45 mg twice a day in adult participants with early and rapidly progressing ALS. Standard of care treatments (e.g. riluzole, edaravone and Nuedexta) will be allowed as long as participants are on a stable dose for at least 4 weeks prior to dosing. In the DBPC period, participants will be randomized in a 3:2 ratio to the pridopidine and placebo arms. In the DBPC period, participants will receive pridopidine or placebo for 48 weeks. In the OLE period, all participants will receive pridopidine for 48 weeks, while maintaining the blind to their original randomization for both the participant as well as the Investigator and other clinical staff. The total study duration per participant will be 102 weeks including screening and follow up. Throughout the study, participants will be assessed through on-site clinic visits and virtual visits (via telephone).
Interventions
DRUGPridopidine
Pridopidine hard gelatin capsule.
DRUGPlacebo
Placebo hard gelatin capsule.
Sponsors
Prilenia
Ferrer Internacional S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized (3:2), double-blind, placebo-controlled study followed by an open-label extension period. During the open-label extension, all participants will receive pridopidine.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Definite ALS or Probable ALS using the El Escorial criteria. * Symptom onset of ≤18 months at screening. * Slow vital capacity (SVC) greater or equal to 60% predicted. * Treatment Research Initiative to Cure ALS (TRICALS) Risk Profile Calculator score, based on the European Network for the Cure of ALS (ENCALS) survival prediction model, in the range of -6 to -2, inclusive, at screening. * Able to swallow a capsule. Key
Exclusion criteria
* Presence of tracheostomy or permanent assisted ventilation. * Clinically significant heart disease, clinically significant history of arrhythmia, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia, or presence of left bundle branch block. * Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the participant to provide informed consent and participate in the study. * Clinically significant and/or unstable medical condition (other than ALS) that may either pose a clinically meaningful risk to the participant and/or to study completion. * Use of medications that prolong QT interval. * Previous treatment with pridopidine, gene therapy, or antisense oligonucleotides. * Confirmed mutation in the SOD1, FUS or C9orf72 gene. * Pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline through Week 26 and Week 48 in the Revised ALS Functional Rating Scale (ALSFRS-R) total score adjusted for mortality | Baseline to Week 48 | The ALSFRS-R encompasses 12 questions grouped into 4 domains to assess bulbar symptoms, limb and trunk functionality, respiratory symptoms, and the need for percutaneous endoscopic gastrostomy (PEG), non-invasive ventilation, or tracheostomy with invasive ventilation. Each function is scored from 0 (no ability) to 4 (normal), with a minimum total score of 0 and maximum total score of 48. Higher scores indicate better functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival at Week 96 | Baseline to Week 96 | Time to death in days from baseline as assessed at the end of open-label extension (OLE) period |
| Change from baseline through Week 26 and Week 48 in speaking rate as measured by quantitative speech assessment in the clinic | Baseline to Week 48 | — |
| Change from baseline through Week 48 in intelligibility of speech by quantitative speech assessment in the clinic. | Baseline to Week 48. | — |
| Change from baseline through Week 48 in percent predicted slow vital capacity (SVC) | Baseline to Week 48 | SVC measures the maximal amount of air exhaled in a relaxed expiration from full inspiration to residual volume. SVC is assessed in the sitting position with a spirometer. |
| Change from baseline through Week 48 in the Bulbar subdomain of the ALSFRS-R | Baseline to Week 48 | Measures decline in bulbar function. |
| Change from baseline through Week 48 in the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 40 (ALSAQ-40) | Baseline to Week 48 | ALSAQ-40 includes 40 items/questions with 5 discrete scales including physical mobility (10 items), activities of daily living and independence (10 items), eating and drinking (3 items), communication (7 items), and emotional reactions (10 items). The questions refer to two weeks prior to the day of the application and the answers are given according to the following variables: never, rarely, sometimes, frequently and always. The score ranges from 0 to 100; the higher the score, the worse the quality of life. |
Countries
United States
Contacts
CONTACTExecutive Director Clinical Operations
Outcome results
None listed