A Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of Prosetin in Healthy Volunteers and Participants With ALS

NCT05279755 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: PRO-101CDMRP-AL2401752023-507363-20-00
• Study Type: interventional
• Target: 72
• Locations: 3 countries
• Sites: 4

Brief Summary

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

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Amyotrophic lateral sclerosis; MAP4K; prosetin

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (5)

• 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

Study Arms (7)

Part A - single dose of placebo

PLACEBO COMPARATOR

Healthy volunteers were administered a single dose of prosetin-matched placebo oral solution.

Drug: placebo

Part A - single ascending doses of prosetin

EXPERIMENTAL

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

Part B - multiple doses of placebo

PLACEBO COMPARATOR

Healthy volunteers were administered a once-daily dose of prosetin-matched placebo for 14 days.

Drug: placebo

Part B - multiple ascending doses of prosetin

EXPERIMENTAL

Healthy volunteers were administered a once-daily dose of prosetin at 0.06 or 0.10 mg/kg for 14 days.

Drug: prosetin

Part C - multiple doses of placebo in participants with ALS

PLACEBO COMPARATOR

Participants are administered a once-daily dose of prosetin-matched placebo for 14 days.

Drug: placebo

Part C - multiple ascending doses of prosetin in participants with ALS

EXPERIMENTAL

Participants will be administered a once-daily dose of prosetin at multiple ascending dose levels for 14 days.

Drug: prosetin

Part D - open-label administration of prosetin in participants with ALS

EXPERIMENTAL

Participants will be administered a once-daily dose of prosetin for up to 52 weeks.

Drug: prosetin

Interventions

prosetin DRUG

oral solution

Part A - single ascending doses of prosetin; Part B - multiple ascending doses of prosetin; Part C - multiple ascending doses of prosetin in participants with ALS; Part D - open-label administration of prosetin in participants with ALS

placebo DRUG

oral solution

Part A - single dose of placebo; Part B - multiple doses of placebo; Part C - multiple doses of placebo in participants with ALS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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
• 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.

Sponsors & Collaborators

• ProJenX: lead
• Congressionally Directed Medical Research Programs: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Worldwide Clinical Trials Early Phase Services

San Antonio, Texas, 78217, United States

Location

The Neuro - Montréal Neurological Institute-Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 30446391 BACKGROUND

• 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.

  PMID: 31676236 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2022
• First Posted: March 15, 2022
• Study Start: February 26, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); US (2); CA (1)