A Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of Prosetin in Healthy Volunteers and Participants With ALS (PRO-101)

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

The primary purpose of this study is to evaluate the safety and tolerability of prosetin in healthy volunteers and participants with ALS.

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: placebo; Drug: prosetin

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.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • The Neuro - Montréal Neurological Institute-Hospital
• Netherlands
  • Utrecht
    • Utrecht, Utrecht, Netherlands, 3584 CX
      • University Medical Center Utrecht
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials Early Phase Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part A - single dose of placebo; Healthy volunteers were administered a single dose of prosetin-matched placebo oral solution.	Drug: placebo; oral solution
Experimental: Part A - single ascending doses of prosetin; Healthy volunteers were administered a single dose of prosetin oral solution at 0.03, 0.06, 0.12, or 0.24 mg/kg.	Drug: prosetin; oral solution
Placebo Comparator: Part B - multiple doses of placebo; Healthy volunteers were administered a once-daily dose of prosetin-matched placebo for 14 days.	Drug: placebo; oral solution
Experimental: Part B - multiple ascending doses of prosetin; Healthy volunteers were administered a once-daily dose of prosetin at 0.06 or 0.10 mg/kg for 14 days.	Drug: prosetin; oral solution
Placebo Comparator: Part C - multiple doses of placebo in participants with ALS; Participants are administered a once-daily dose of prosetin-matched placebo for 14 days.	Drug: placebo; oral solution
Experimental: Part C - multiple ascending doses of prosetin in participants with ALS; Participants will be administered a once-daily dose of prosetin at multiple ascending dose levels for 14 days.	Drug: prosetin; oral solution
Experimental: Part D - open-label administration of prosetin in participants with ALS; Participants will be administered a once-daily dose of prosetin for up to 52 weeks.	Drug: prosetin; oral solution

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: ProJenX
• Collaborators: Congressionally Directed Medical Research Programs

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: March 6, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: ALS; Amyotrophic lateral sclerosis; MAP4K; prosetin
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: PRO-101; 2023-507363-20-00 (Ctis); CDMRP-AL240175 (Other Grant/Funding Number: Congressionally Directed Medical Research Programs)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No