A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Usnoflast in Adults with Amyotrophic Lateral Sclerosis
- Trial ID
- 2025-522580-15-00
- Protocol
- USNO.24.002
- Sponsor
- Zydus Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the efficacy of Usnoflast compared to placebo in adults with Amyotrophic Lateral Sclerosis (ALS), specifically measuring the ALSFRS-R total score and survival (5). The secondary objectives include:
- Assessment of slow vital capacity (SVC).
- Evaluation of serum and cerebrospinal fluid (CSF) levels of neurofilament light (NfL) protein.
- Analysis of ALSFRS-R total score and specific functional domains.
- Comparison of health-related quality of life.
- Evaluation of safety and tolerability (4).
- Assessment of pharmacokinetics (6) in plasma and CSF.
- Evaluation of survival.
Participants
The study population consists of 38 participants diagnosed with Amyotrophic Lateral Sclerosis. The cohort includes both male and female subjects within the age ranges corresponding to codes 3 and 4. Inclusion requires a diagnosis of probable or definite disease according to the revised El Escorial criteria. Eligible participants must have experienced the onset of the first symptom for 24 months or less and possess an ALSFRS-R score of at least 35 at screening. Respiratory function must be maintained with a forced vital capacity of at least 60% of the predicted value. Participants must be able to swallow capsules and may be receiving stable doses of riluzole, sodium phenylbutyrate, taurursodiol, tofersen, or edaravone for a specified period prior to the screening visit.
Plans and Procedures
This phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study is designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of Usnoflast in adults diagnosed with Amyotrophic Lateral Sclerosis. The methodology involves comparing the test product against a placebo administered via oral use in capsule form. The primary endpoints include changes in disease progression as measured by the ALSFRS-R total score and survival over a 36-week period. Secondary assessments include changes in forced vital capacity, serum levels of NfL protein, and ALSAQ-40 scores. The study sequence begins with a screening visit to verify eligibility based on diagnosis, symptom onset, and stable medication status. Following screening, subjects undergo treatment through a 36-week observation period, which includes assessments of plasma and cerebrospinal fluid. The total duration of participant involvement is centered around this 36-week treatment window.
Treatment
The experimental treatment consists of Usnoflast, administered as a capsule via the oral route. This substance is classified as an orphan drug for the treatment of Amyotrophic Lateral Sclerosis.
The control group receives a placebo, which is manufactured to be identical to the Usnoflast capsules in terms of size, shape, and color.
Efficacy
The efficacy of Usnoflast in subjects with Amyotrophic Lateral Sclerosis will be evaluated through several parameters. The primary endpoint is the change in disease progression from baseline through 36 weeks, assessed via the ALSFRS-R total score and survival.
Secondary efficacy assessments include:
- Change in forced vital capacity (SVC) from baseline to Week 36.
- Change in serum levels of neurofilament light protein (NfL) from baseline to Week 36.
- Change in various functional items or domains of the ALSFRS-R total score from baseline to Week 36.
- Change in the ALSAQ-40 score from baseline to Week 36.
- Change in cerebrospinal fluid (CSF) levels of NfL protein from baseline to Week 36.
- Time from baseline to the occurrence of death or permanent alveolar ventilation (PAV), defined as >22 hours daily for >7 days, through Week 36.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and/or female subjects aged 18 years or older at screening
- Diagnosis of probable or definite ALS, according to the revised version of the El Escorial World Federation of Neurology criteria
- Time since onset of first symptom of ALS ≤24 months
- ALSFRS-R score of ≥35 at screening
- SVC: ≥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
Exclusion Criteria
- 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
- 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 ALS at any time in the past
- Following laboratory test values at screening: - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >3.0 × upper limit of normal (ULN) - Bilirubin >1.5 × ULN unless the subject has documented Gilbert’s syndrome (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated, and direct bilirubin is <35%) - Estimated glomerular filtration rate <60 mL/min/1.73 m2
- For those participating in the optional CSF collection, contraindications to lumbar puncture including but not limited to lumbar scoliosis, coagulopathy, infection at site of puncture, or use of anticoagulants.
- Subjects with history of epilepsy within 6 months of screening visit.
- Surgery within last 3 months or planned major surgery within next 3 months from the date of screening (other than minor cosmetic surgery and minor dental surgery).
- 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 ALS, precluding safe participation of subject in this study in the opinion of the investigator
- Known allergy, sensitivity, or intolerance to IP or excipients
- Subjects who have taken concomitant medications that are substrates of drug metabolizing enzymes (CYP1A2 and/or CYP2B6) within 7 days or 5 half-lives of the medication (whichever is longer) before the first dose of IP 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 IP administration
- Use of any investigational drug concurrently or within 4 weeks or 5 half-lives (whichever is longer), prior to the first dose of IP administration
- Use or intended use of any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John’s Wort, within 4 weeks of screening and up to end of study. Use of such medication will be considered on a case-by-case basis as per the opinion of the investigator and/or independent medical monitor.
- Receiving an elemental diet or parenteral nutrition.
- Received blood transfusion within 3 months prior to screening.
- Subjects with HIV, hepatitis B, hepatitis C, coronary artery disease, or active gastrointestinal condition that might interfere with drug absorption
- Inability to be venipunctured or those not able to tolerate venous puncture
- Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of employees of investigator or the investigator.
- Any condition not mentioned in any of the above criteria that, as per the investigator, would hinder participation of the subject in the study. This may include, but not limited to, considerations of safety, compliance, or other factors that could impact the integrity of the study or the well-being of the subject
- If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or of child-bearing potential and unwilling to use effective contraception during the study and for at least 1 month after administration of last dose of IP. If male of reproductive capacity, unwilling to use effective contraception during the study and for at least 1 month after administration of last dose of IP
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 23 Feb 2026 | 10 |
 France | Recruiting | 23 Feb 2026 | 40 |
 Germany | Not Yet Recruiting | 23 Feb 2026 | 20 |
 Ireland | Not Yet Recruiting | 23 Feb 2026 | 12 |
 Italy | Not Yet Recruiting | 23 Feb 2026 | 40 |
 The Netherlands | Recruiting | 23 Feb 2026 | — |
 Poland | Recruiting | 23 Feb 2026 | 12 |
 Spain | Not Yet Recruiting | 23 Feb 2026 | 30 |
 Sweden | Recruiting | 23 Feb 2026 | 12 |
| Netherlands | — | — | 30 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Usnoflast | Test | CAPSULE | ORAL USE | 0 | 374 | PRD12980113 |
Placebo will be identical to Usnoflast capsules in terms of size, shape, and color. | Placebo | N/A | — | — | — | N/A |
Usnoflast | Test | CAPSULE | ORAL USE | 0 | 374 | PRD12980114 |