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

NCT ID: NCT05279755

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-26
• Study Completion Date: 2026-10-31

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A - single dose of placebo

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

oral solution

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.

Group Type: EXPERIMENTAL

prosetin

Intervention Type: DRUG

oral solution

Part B - multiple doses of placebo

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

oral solution

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.

Group Type: EXPERIMENTAL

prosetin

Intervention Type: DRUG

oral solution

Part C - multiple doses of placebo in participants with ALS

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

oral solution

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.

Group Type: EXPERIMENTAL

prosetin

Intervention Type: DRUG

oral solution

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.

Group Type: EXPERIMENTAL

prosetin

Intervention Type: DRUG

oral solution

Interventions

prosetin

oral solution

Intervention Type: DRUG

placebo

oral solution

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

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

Exclusion Criteria

• 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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Congressionally Directed Medical Research Programs

FED

Sponsor Role: collaborator

ProJenX

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Worldwide Clinical Trials Early Phase Services

San Antonio, Texas, United States

Site Status: COMPLETED

The Neuro - Montréal Neurological Institute-Hospital

Montreal, Quebec, Canada

Site Status: RECRUITING

University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

Site Status: RECRUITING

Countries

United States; Canada; Netherlands

Central Contacts

ProJenX Clinical Trials

Role: CONTACT

trials@projenx.com

(917) 423-6476

Facility Contacts

Mary McCormack

Role: primary

mmccormack12@mgh.harvard.edu

617-726-1398

Shyanne Hill

Role: backup

sthill@mgh.harvard.edu

617-643-5376

Role: primary

als-cru.neuro@mcgill.ca

514-398-6183

Role: primary

trialALS@umcutrecht.nl

+31 88 755 3204

References

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.

Reference Type: BACKGROUND

PMID: 30446391 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31676236 (View on PubMed)

Other Identifiers

CDMRP-AL240175

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2023-507363-20-00

Identifier Type: CTIS

Identifier Source: secondary_id

PRO-101

Identifier Type: -

Identifier Source: org_study_id