Usnoflast Neuromuscular Investigation for Treatment Efficacy in Amyotrophic Lateral Sclerosis

NCT07023835 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: USNO.24.002
• Study Type: interventional
• Target: 240
• Locations: 2 countries
• Sites: 17

Brief Summary

Usnoflast Neuromuscular Investigation for Treatment Efficacy in Amyotrophic Lateral Sclerosis

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Amyotrophic Lateral Sclerosis,; ALS; Usnoflast

Outcome Measures

Primary Outcomes (5)

• Efficacy of Usnoflast versus placebo assessed using the revised ALSFRS-R total score

  Change in disease progression from baseline through Week 36 as measured by ALSFRS-R total score

  From baseline through Week 36

• Efficacy of Usnoflast versus placebo assessed using the survival

  Change in disease progression from baseline through Week 36 as measured by survival Survival is defined based on the time of death or permanent-assisted ventilation (PAV). PAV is defined as the use of invasive or noninvasive mechanical ventilation for \>22 hours daily for \>7 consecutive days

  From baseline through Week 36

• Effect of Usnoflast versus placebo on survival in Open label extension phase

  Time from baseline to the occurrence of death or Permanent-assisted ventilation (\>22 hours daily for \>7 days)

  From baseline through Week 16

• Number of participants with treatment emergent adverse events in open label extension

  Time from baseline

  From baseline through Week 16

• Number of participants with Serious adverse events in open label extension

  Time from baseline

  From baseline through Week 16

Secondary Outcomes (18)

• Effect of Usnoflast versus placebo on survival

  From baseline through Week 36

• Evaluate the effect of Usnoflast versus placebo on Slow vital capacity

  from baseline to Week 36

• Evaluate the effect of Usnoflast versus placebo on serum levels of Neurofilament light chain protein

  From baseline to Week 36

• Evaluate the effect of Usnoflast versus placebo on Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score and various functional items/domains of the ALSFRS-R total score

  From baseline to Week 36

• Evaluate and compare the effect of Usnoflast versus placebo on overall health-related quality of life

  From baseline to Week 36

Study Arms (3)

50 mg Usnoflast

ACTIVE COMPARATOR

50 mg Usnoflast capsules and matching placebo of 25 mg capsule under fasting conditions twice a day orally for 36 weeks

Drug: 50 mg Usnoflast

75 mg Usnoflast

ACTIVE COMPARATOR

25 mg + 50 mg Usnoflast capsules under fasting conditions twice a day orally for 36 weeks

Drug: 75 mg Usnoflast

Placebo

PLACEBO COMPARATOR

Matching placebo of 25 mg and 50 mg under fasting conditions twice a day orally for 36 weeks

Drug: Placebo

Interventions

50 mg Usnoflast DRUG

50 mg Usnoflast (50 mg Usnoflast capsules and matching placebo of 25 mg capsule)

Also known as: Not any

50 mg Usnoflast

75 mg Usnoflast DRUG

75 mg Usnoflast (25 mg + 50 mg Usnoflast capsules)

Also known as: Not any

75 mg Usnoflast

Placebo DRUG

Matching placebo of 25 mg and 50 mg

Also known as: Not any

Placebo

Eligibility Criteria

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

You may qualify if:

• Diagnosis of probable or definite Amyotrophic lateral sclerosis, according to the revised version of the El Escorial World Federation of Neurology criteria
• Time since onset of first symptom of Amyotrophic lateral sclerosis ≤24 months. Date of Amyotrophic lateral sclerosis symptom onset. For the purposes of this study, the date of symptom onset will be defined as the date the subject first had symptoms of their disease, i.e., limb weakness, dysarthria, dysphagia, shortness of breath, or fasciculations, from the screening visit.
• Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score of ≥35 at screening.
• Slow vital capacity: ≥60% of predicted capacity at the screening visit.
• Be able to swallow capsules.
• Either not currently receiving riluzole/sodium phenylbutyrate and taurursodiol/tofersen or on a stable dose of riluzole/sodium phenylbutyrate and taurursodiol/tofersen for at least 4 weeks before the screening visit. Subjects receiving riluzole/sodium phenylbutyrate and taurursodiol/tofersen are expected to remain on the same dose throughout the duration of the study.
• Either not currently receiving edaravone or on edaravone treatment. Subjects receiving edaravone must have completed at least 1 cycle of treatment before the screening visit and are expected to continue with a stable dose of edaravone treatment throughout the duration of the study.
• Capable of providing informed consent and complying with study procedures in the opinion of the investigator

You may not qualify if:

• Presence of unstable psychiatric disease, cognitive impairment, dementia, or substance abuse that would impair the ability of the subject to provide informed consent, in the opinion of the investigator.
• Serious illness (e.g., pneumonia, septicemia) within 4 weeks of the screening visit; infection requiring hospitalization or treatment with intravenous antibiotics, antivirals, or antifungals within 4 weeks of screening; chronic bacterial infection (such as tuberculosis) deemed unacceptable as per the judgment of the investigator.
• Active herpes zoster infection within 2 months prior to the screening visit.
• Any medical condition that promotes suicidal attempt or behavior within 6 months prior to the screening visit and in the opinion of the investigator might interfere with subject's participation in the study or is a risk for a suicide attempt.
• History of unstable or severe cardiac, pulmonary, oncological, hepatic, or renal disease or active cancer or another medically significant illness other than Amyotrophic lateral sclerosis, precluding safe participation of subject in this study in the opinion of the investigator.
• Known allergy, sensitivity, or intolerance to Investigational product or excipients.
• Subjects who have taken concomitant medications that are substrates of drug metaboliz-ing enzymes (Cytochrome P450 1A2 and/or Cytochrome P450 2B6) within 7 days or 5 half-lives of the medication (whichever is longer) before the first dose of Investigational product and throughout the study.
• Use of any steroids, colchicine, or anti-IL-1 inhibitors within 7 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of Investigational product administration.
• Use of any investigational drug concurrently or within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of Investigational product administration.
• Any clinically significant condition and/or laboratory significant value that would prevent the subject from participating in the study in the opinion of the investigator.
• Received a live vaccine within 14 days before the screening visit or planning to receive during the study duration.
• Subjects who have received stem cell or gene therapy for Amyotrophic lateral sclerosis at any time in the past.
• Following laboratory test values at screening:
• Alanine aminotransferase or Aspartate aminotransferase values \>3.0 × Upper Limit of Normal
• Bilirubin \>1.5 × Upper Limit of Normal unless the subject has documented Gilbert's syndrome (isolated bilirubin \>1.5 × Upper Limit of Normal is acceptable if bilirubin is fractionated, and direct bilirubin is \<35%)

Sponsors & Collaborators

• Zydus Therapeutics Inc.: lead

Study Sites (17)

Zydus US015

La Jolla, California, 92037, United States

Location

Zydus US008

Orange, California, 92868, United States

Location

Zydus US013

San Francisco, California, 94109, United States

Location

Zydus US005

New Britain, Connecticut, 06053, United States

Location

Zydus US012

Tampa, Florida, 80045, United States

Location

Zydus US007

Atlanta, Georgia, 30322, United States

Location

Zydus US010

Boston, Massachusetts, 02114, United States

Location

Zydus US006

Detroit, Michigan, 48202, United States

Location

Zydus US014

Lincoln, Nebraska, 68510, United States

Location

Zydus US003

Winston-Salem, North Carolina, 27157, United States

Location

Zydus 009

Pittsburgh, Pennsylvania, 15212, United States

Location

Zydus US001

Dallas, Texas, 75206, United States

Location

Zydus US002

Houston, Texas, 77030, United States

Location

Zydus US004

Richmond, Virginia, 23298, United States

Location

Zydus US011

Seattle, Washington, 98122, United States

Location

Zydus 101

Toronto, Ontario, ON M4N 3M5, Canada

Location

Zydus 100

Québec, Quebec, QC H4A 3T2, Canada

Location

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 Officials

• Deven V Parmar

  Zydus Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, multicenter

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: June 17, 2025
• Study Start: September 17, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2025-12

Locations

CA (2); US (15)