Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Amyotrophic lateral sclerosis, MAP4K, prosetin
Brief summary
The primary purpose of this study is to evaluate the safety and tolerability of prosetin in healthy volunteers and participants with ALS.
Detailed description
PRO-101 is a four-part study. Parts A and B, which respectively evaluated the safety, tolerability, and PK of single and multiple ascending doses of prosetin in 48 healthy volunteers, have been completed. Parts C and D, which are ongoing, will evaluate the effects of prosetin on safety, tolerability, PK, and biomarkers in 24 participants with ALS. Part C is a double-blind, placebo-controlled, multiple ascending dose component of the study, and Part D is an optional 52-week open-label extension available to ALS participants who complete 14 days of dosing in Part C.
Interventions
DRUGprosetin
oral solution
DRUGplacebo
oral solution
Sponsors
ProJenX
Congressionally Directed Medical Research Programs
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Parts A, B, and C of PRO-101 are double-blind, dose escalating portions of the study. Part D is an open-label extension in which no parties are masked and all participants receive the study drug.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
PRO-101, Parts A and B, were completed in healthy volunteers. PRO-101, Parts C and D are ongoing in participants with ALS. Key eligibility criteria are summarized below: Key Inclusion Criteria - Part C * Adults ≥18 years of age * Diagnosis of ALS based on the Gold Coast diagnostic criteria * Slow Vital Capacity (SVC) \>50% predicted * If being concomitantly treated with riluzole and/or locally approved standard of care treatments, the participant must be on a stable dose for at least 30 days prior to screening and throughout the study * In the opinion of the Investigator, participant is able to swallow liquid in order to ingest the study medication. Key
Exclusion criteria
- Part C * Active dementia, neurologic diseases other than ALS, or psychiatric illness that in the opinion of the investigator would affect participation in the current study. * Significant history or clinical manifestation of comorbid disease in any organ system that currently requires active treatment or is likely to require treatment during the study. * Any episodes of vertigo in the previous 12 months prior to screening. * Any medical history of seizures, or any clinically significant EEG finding at Screening or at Day -1. * A diagnosis of cancer or evidence of continued disease within five years before screening. Protocol-specified exceptions may be considered with approval from the Sponsor's Medical Monitor. * Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days prior to the first dose of study medication. * Prior exposure to any stem cell or gene therapies (investigational or off-label) for the treatment of ALS. Key Inclusion Criteria- Part D Participants who meet all of the following criteria may be included in Part D of the study: * Participants must have completed 14 days of blinded treatment in Part C. * Participants taking approved ALS standard-of-care medications must remain on stable doses through Day 28 of open-label treatment. * In the judgment of the Investigator, the participant's participation in the open-label portion of the study is medically appropriate Key
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts A, B, C, D: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks |
| Parts A, B, C, D: Number of Participants with Clinically Significant Laboratory Test Abnormalities | Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks |
| Parts A, B, C, D: Number of Participants with Clinically Significant Vital Signs Abnormalities | Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks |
| Parts A, B, C, and D: Number of Participants with Clinically Significant Electrocardiogram (ECG) Abnormalities | Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks |
| Parts A, B, C, and D: Number of Participants with Clinically Significant Physical Examination Abnormalities | Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks |
| Parts A, B, C, and D: Number of Participants with Clinically Significant Neurological Examination Abnormalities | Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks |
| Parts A, B, C, and D: Number of Participants with Clinically Significant Ophthalmic Examination Abnormalities | Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks |
| Parts C and D: Number of Participants with Clinically Significant Electroencephalogram (EEG) Abnormalities | Part C: Up to 28 days; Part D: Up to 54 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Parts A, B, C, and D: Maximum Observed Concentration (Cmax) of Prosetin in Plasma | Part A: Up to 28 days Part B: Up to 42 days Part C: Up to 28 days Part D: Up to 54 weeks |
| Parts A, B, C, and D: Time to Reach Maximum Observed Concentration (Tmax) of Prosetin in Plasma | Part A: Up to 28 days Part B: Up to 42 days Part C: Up to 28 days Part D: Up to 54 weeks |
| Parts A, B, C, and D: Area Under the Concentration-Time Curve (AUC) of Prosetin in Plasma | Part A: Up to 28 days Part B: Up to 42 days Part C: Up to 28 days Part D: Up to 54 weeks |
| Parts A, B, C, and D: Apparent Terminal Elimination Half-life (t1/2) of Prosetin in Plasma | Part A: Up to 28 days Part B: Up to 42 days Part C: Up to 28 days Part D: Up to 54 weeks |
| Parts A and D: Measure of Concentration of Prosetin in CSF | Part A: Day 1; Part D: Up to 48 weeks |
Countries
Canada, Netherlands, United States
Outcome results
None listed