USNOFLAST for Amyotrophic lateral sclerosis

Inclusion criteria

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

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Change in disease progression from baseline through 36 weeks, as measured by ALSFRS-R total score and survival","definition_or_measurement_approach":"Measured by change in ALSFRS-R total score from baseline through 36 weeks and by survival (time to death) over the same 36-week period."}

Secondary endpoints

• {"endpoint_text":"- 1. Change in SVC from baseline to Week 36","definition_or_measurement_approach":"Change in slow vital capacity (SVC) from baseline to Week 36."}
• {"endpoint_text":"- 2. Change in serum levels of NfL protein from baseline to Week 36","definition_or_measurement_approach":"Change in serum neurofilament light (NfL) protein levels from baseline to Week 36."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in ALSFRS-R total and domain/item scores from baseline to Week 36."}
• {"endpoint_text":"- 4. Change in ALSAQ-40 score from baseline to Week 36","definition_or_measurement_approach":"Change in ALSAQ-40 health-related quality of life score from baseline to Week 36."}
• {"endpoint_text":"- 5. Number of TEAEs and SAEs up to Week 36","definition_or_measurement_approach":"Count and reporting of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) through Week 36."}
• {"endpoint_text":"- 6. Assessment of PK in plasma (baseline, Week 16, and Week 36) and CSF (baseline, Week 16, and Week 36)","definition_or_measurement_approach":"Pharmacokinetic assessments in plasma and CSF at baseline, Week 16 and Week 36."}
• {"endpoint_text":"- 7. Change in CSF levels of NfL protein from baseline to Week 36","definition_or_measurement_approach":"Change in CSF neurofilament light (NfL) protein levels from baseline to Week 36."}
• {"endpoint_text":"- 8. Time from baseline to the occurrence of death or PAV (>22 hours daily for >7 days) (from baseline through Week 36)","definition_or_measurement_approach":"Time-to-event measure from baseline to death or permanent assisted ventilation (PAV) defined as >22 hours daily for >7 days, assessed through Week 36."}

Methods

• Country-specific recruitment arrangements documents (K1) — available for multiple countries (DEU, ITA, NLD, FRA, BEL, ESP, SWE, IE, POL).
• Flyers (ALS Flyer) — patient-targeted printed/handout materials (country-specific versions present: DEU, BEL, NLD, FRA, ITA, IE, POL, SWE, ESP).
• Recruitment brochures — patient-targeted brochures (country-specific versions present).
• Patient letters and Thank You cards — patient-targeted postal/email outreach materials (country-specific versions present).
• Doctor/Physician letters and GP letters — clinician-targeted recruitment outreach (country-specific versions present).
• Pre-ICF Telephone Data Consent (telephone pre-screening/consent information) — country-specific documents available (e.g., Belgium).
• Use of third-party vendor PPD Acurian for patient retention and recruitment materials (named in sponsor/third-party duties).

Spain

Earliest CTIS Part Ii Submission Date

26-02-2026

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

78

Number Of Sites

4

Number Of Participants

30

Germany

Earliest CTIS Part Ii Submission Date

06-02-2026

Latest Decision Or Authorization Date

18-03-2026

Processing Time Days

40

Number Of Sites

6

Number Of Participants

20

Italy

Earliest CTIS Part Ii Submission Date

24-02-2026

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

27

Number Of Sites

5

Number Of Participants

40

Netherlands

Earliest CTIS Part Ii Submission Date

20-02-2026

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

33

Number Of Sites

1

Number Of Participants

30

France

Earliest CTIS Part Ii Submission Date

13-01-2026

Latest Decision Or Authorization Date

12-03-2026

Processing Time Days

58

Number Of Sites

7

Number Of Participants

40

Belgium

Earliest CTIS Part Ii Submission Date

25-02-2026

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

20

Number Of Sites

1

Number Of Participants

10

Ireland

Earliest CTIS Part Ii Submission Date

16-03-2026

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

60

Number Of Sites

1

Number Of Participants

12

Poland

Earliest CTIS Part Ii Submission Date

24-02-2026

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

80

Number Of Sites

2

Number Of Participants

12

Sweden

Earliest CTIS Part Ii Submission Date

24-02-2026

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

80

Number Of Sites

3

Number Of Participants

12

Primary sponsor

Full Name

Zydus Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

Global Clinical Supplies (for IP and Non-IP Study Supplies), PPD Acurian (Patient retention and recruitment materials), PPD BioA and PPD Laboratories (for Safety Samples and Serum & CSF NFL anlysis), PPD Safety (for safety reporting)

Name

Cliantha Research Limited

Name

4g Clinical LLC

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Global Clinical Supplies (for IP and Non-IP Study Supplies), PPD Acurian (Patient retention and recruitment materials), PPD BioA and PPD Laboratories (for Safety Samples and Serum & CSF NFL anlysis), PPD Safety (for safety reporting)","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Cliantha Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"eDiaries, Rater training","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"India","full_name":"Zydus Lifesciences Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Travel/reimbursment","organisation_type":"Hospital/Clinic/Other health care facility"}