Usnoflast Neuromuscular Investigation for Treatment Efficacy in ALS (UNITE-ALS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zydus Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-03-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Zydus Therapeutics Inc.

External identifiers

EU CT number

2025-522580-15-00

ClinicalTrials.gov

NCT07023835

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic

To evaluate the efficacy of Usnoflast versus placebo, using the ALSFRS-R total score and survival

Secondary objectives 8

1. 1. To evaluate the effect of Usnoflast versus placebo on SVC
2. 2. To evaluate the effect of Usnoflast versus placebo on serum levels of NfL protein
3. 3. To evaluate the effect of Usnoflast versus placebo on ALSFRS-R total score and various functional items/domains of the ALSFRS-R total score
4. 4. To evaluate and compare the effect of Usnoflast versus placebo on overall health-related quality of life
5. 5. To compare the safety and tolerability of Usnoflast versus placebo
6. 6. To evaluate the PK of Usnoflast in plasma and CSF
7. 7. To evaluate the effect of Usnoflast versus placebo on CSF levels of NfL protein
8. 8. To evaluate the effect of Usnoflast versus placebo on survival

Conditions and MedDRA coding

Amyotrophic Lateral Sclerosis (ALS)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Male and/or female subjects aged 18 years or older at screening
2. 2. Diagnosis of probable or definite ALS, according to the revised version of the El Escorial World Federation of Neurology criteria
3. 3. Time since onset of first symptom of ALS ≤24 months
4. 4. ALSFRS-R score of ≥35 at screening
5. 5. SVC: ≥60% of predicted capacity at the screening visit
6. 6. Be able to swallow capsules
7. 7. 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
8. 8. 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
9. 9. Capable of providing informed consent and complying with study procedures in the opinion of the investigator

Exclusion criteria 24

1. 1. 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
2. 10. 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
3. 11. Received a live vaccine within 14 days before the screening visit or planning to receive during the study duration.
4. 12. Subjects who have received stem cell or gene therapy for ALS at any time in the past
5. 13. 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
6. 14. 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.
7. 15. Subjects with history of epilepsy within 6 months of screening visit.
8. 16. 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).
9. 2. 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
10. 3. Active herpes zoster infection within 2 months prior to the screening visit
11. 4. 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
12. 5. 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
13. 6. Known allergy, sensitivity, or intolerance to IP or excipients
14. 7. 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
15. 8. 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
16. 9. 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
17. 17. 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.
18. 18. Receiving an elemental diet or parenteral nutrition.
19. 19. Received blood transfusion within 3 months prior to screening.
20. 20. Subjects with HIV, hepatitis B, hepatitis C, coronary artery disease, or active gastrointestinal condition that might interfere with drug absorption
21. 21. Inability to be venipunctured or those not able to tolerate venous puncture
22. 22. 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.
23. 23. 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
24. 24. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in disease progression from baseline through 36 weeks, as measured by ALSFRS-R total score and survival

Secondary endpoints 8

1. 1. Change in SVC from baseline to Week 36
2. 2. Change in serum levels of NfL protein from baseline to Week 36
3. 3. Change in ALSFRS-R total score and scores of various functional items/domains of the ALSFRS-R total score from baseline to Week 36
4. 4. Change in ALSAQ-40 score from baseline to Week 36
5. 5. Number of TEAEs and SAEs up to Week 36
6. 6. Assessment of PK in plasma (baseline, Week 16, and Week 36) and CSF (baseline, Week 16, and Week 36)
7. 7. Change in CSF levels of NfL protein from baseline to Week 36
8. 8. Time from baseline to the occurrence of death or PAV (>22 hours daily for >7 days) (from baseline through Week 36)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Zydus Therapeutics Inc.

Sponsor organisation

Zydus Therapeutics Inc.

Address

73c Route 31 North

City

Pennington

Postcode

08534-3601

Country

United States

Scientific contact point

Organisation

Zydus Therapeutics Inc.

Contact name

Dr. Deven Parmar

Public contact point

Organisation

Zydus Therapeutics Inc.

Contact name

Priya Kalluri

Third parties 7

Locations

9 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 129 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications