Clinical trial NCT05279755: A Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of Prosetin in Healthy Volunteers and Participants With ALS
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalating Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending and Multiple Ascending Doses of Prosetin in Healthy Volunteers and Participants With Amyotrophic Lateral Sclerosis (ALS) With an Optional Open-Label Extended Treatment Period for ALS Participants Who Complete 14 Days of Blinded Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Amyotrophic lateral sclerosis
MAP4K
prosetin
Lead sponsor: ProJenX
Sponsor class: INDUSTRY
Collaborators: name: Congressionally Directed Medical Research Programs
First posted: 2022-03-15
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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 Exclusion Criteria- Part D

* Treatment with any other investigational drug or device throughout the duration of the study is excluded, with the exception of any COVID-19 vaccine or treatment with an emergency use authorization.

NOTE: Other protocol-defined Inclusion/Exclusion Criteria may apply. Please contact trials@projenx.com with any questions about eligibility criteria.

Primary outcomes:
measure: Parts A, B, C, D: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks
measure: Parts A, B, C, D: Number of Participants with Clinically Significant Laboratory Test Abnormalities
timeFrame: Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks
measure: Parts A, B, C, D: Number of Participants with Clinically Significant Vital Signs Abnormalities
timeFrame: Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks
measure: Parts A, B, C, and D: Number of Participants with Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks
measure: Parts A, B, C, and D: Number of Participants with Clinically Significant Physical Examination Abnormalities
timeFrame: Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks
measure: Parts A, B, C, and D: Number of Participants with Clinically Significant Neurological Examination Abnormalities
timeFrame: Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks
measure: Parts A, B, C, and D: Number of Participants with Clinically Significant Ophthalmic Examination Abnormalities
timeFrame: Part A: Up to 28 days; Part B: Up to 42 days; Part C: Up to 28 days; Part D: Up to 54 weeks
measure: Parts C and D: Number of Participants with Clinically Significant Electroencephalogram (EEG) Abnormalities
timeFrame: Part C: Up to 28 days; Part D: Up to 54 weeks
Secondary outcomes:
measure: Parts A, B, C, and D: Maximum Observed Concentration (Cmax) of Prosetin in Plasma
timeFrame: Part A: Up to 28 days Part B: Up to 42 days Part C: Up to 28 days Part D: Up to 54 weeks
measure: Parts A, B, C, and D: Time to Reach Maximum Observed Concentration (Tmax) of Prosetin in Plasma
timeFrame: Part A: Up to 28 days Part B: Up to 42 days Part C: Up to 28 days Part D: Up to 54 weeks
measure: Parts A, B, C, and D: Area Under the Concentration-Time Curve (AUC) of Prosetin in Plasma
timeFrame: Part A: Up to 28 days Part B: Up to 42 days Part C: Up to 28 days Part D: Up to 54 weeks
measure: Parts A, B, C, and D: Apparent Terminal Elimination Half-life (t1/2) of Prosetin in Plasma
timeFrame: Part A: Up to 28 days Part B: Up to 42 days Part C: Up to 28 days Part D: Up to 54 weeks
measure: Parts A and D: Measure of Concentration of Prosetin in CSF
timeFrame: Part A: Day 1; Part D: Up to 48 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: San Antonio
country: United States
facility: Worldwide Clinical Trials Early Phase Services
state: Texas
city: Montréal
country: Canada
facility: The Neuro - Montréal Neurological Institute-Hospital
state: Quebec
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
References:
citation: Thams S, Lowry ER, Larraufie MH, Spiller KJ, Li H, Williams DJ, Hoang P, Jiang E, Williams LA, Sandoe J, Eggan K, Lieberam I, Kanning KC, Stockwell BR, Henderson CE, Wichterle H. A Stem Cell-Based Screening Platform Identifies Compounds that Desensitize Motor Neurons to Endoplasmic Reticulum Stress. Mol Ther. 2019 Jan 2;27(1):87-101. doi: 10.1016/j.ymthe.2018.10.010. Epub 2018 Oct 19.
citation: Bos PH, Lowry ER, Costa J, Thams S, Garcia-Diaz A, Zask A, Wichterle H, Stockwell BR. Development of MAP4 Kinase Inhibitors as Motor Neuron-Protecting Agents. Cell Chem Biol. 2019 Dec 19;26(12):1703-1715.e37. doi: 10.1016/j.chembiol.2019.10.005. Epub 2019 Oct 31.