Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZYIL1 in Patients With Amyotrophic Lateral Sclerosis

NCT05981040 | Completed Phase 2

• 1 other identifier: ZYIL1.23.003
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

Brief Summary

ZYIL1 is expected to show benefit in patients with Amyotrophic Lateral Sclerosis (ALS). The present study aims to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of ZYIL1 when administered to subjects with ALS.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the ALSFRS-R total score

  From baseline to Week 12

Secondary Outcomes (8)

• Time from baseline to the occurrence of either death, or permanent assisted ventilation

  Baseline to Week 12 (>22 hours daily for >7 consecutive days), whichever comes first )

• Change from baseline in slow vital capacity (SVC)

  Baseline to Week 12

• Change from baseline in serum neurofilament light chain biomarker

  Baseline to Week 12

• Number of patients with treatment emergent adverse events

  Baseline to Week 12

• Number of patients with Serious adverse event (SAE)

  Baseline to Week 12

Study Arms (4)

Arm 1

ACTIVE COMPARATOR

ZYIL1 capsules 25 mg for oral administration + matching placebo of 50 mg ZYIL1 capsule

Drug: ZYIL1 capsules 25 mg and 50 mg Placebo

Arm 2

ACTIVE COMPARATOR

ZYIL1 capsules 50 mg for oral administration + matching placebo of 25 mg ZYIL1 capsule

Drug: ZYIL1 capsules 50 mg and 25 mg Placebo

Arm 3

ACTIVE COMPARATOR

ZYIL1 capsules 25 mg for oral administration + ZYIL1 capsules 50 mg for oral administration

Drug: ZYIL1 capsules 25 mg and ZYIL1 capsules 50 mg

Arm 4

PLACEBO COMPARATOR

Matching placebo of 25 mg ZYIL1 capsule + Matching placebo of 50 mg ZYIL1 capsule

Drug: Matching placebo 25 mg and Matching placebo 50 mg

Interventions

ZYIL1 capsules 25 mg and 50 mg Placebo DRUG

ZYIL1 capsules 25 mg for oral administration + matching placebo of 50 mg ZYIL1 capsule

Arm 1

ZYIL1 capsules 50 mg and 25 mg Placebo DRUG

ZYIL1 capsules 50 mg for oral administration + matching placebo of 25 mg ZYIL1 capsule

Arm 2

ZYIL1 capsules 25 mg and ZYIL1 capsules 50 mg DRUG

ZYIL1 capsules 25 mg for oral administration + ZYIL1 capsules 50 mg for oral administration

Arm 3

Matching placebo 25 mg and Matching placebo 50 mg DRUG

Matching placebo of 25 mg ZYIL1 capsule + Matching placebo of 50 mg ZYIL1 capsule

Arm 4

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and/or female patients aged between 18 and 80 years (inclusive at screening).
• Diagnosis of probable or definite ALS, according to the revised version of the El Escorial World Federation of Neurology criteria. Refer Appendix III - El Escorial Criteria.
• Time since onset of first symptom of ALS ≤9 months
• Slow Vital Capacity (SVC) ≥ 50% of the predicted value
• Be able to swallow the study capsules during study
• Either not currently receiving riluzole or on a stable dose of riluzole for at least 4 weeks before the screening visit. Participants receiving riluzole are expected to remain on the same dose throughout the duration of the study
• Either not currently receiving edaravone or on edaravone treatment. Participants receiving edaravone must have completed at least 1 cycle of treatment before the screening visit and are expected to continue with stable dose edaravone treatment throughout the duration of the study.
• Female patients must be non-pregnant, non-lactating and women of child-bearing potential/ sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal\* for at least 12 consecutive months, must agree to use adequate contraception (hormonal contraceptives \[combined estrogen and progestogen oral contraceptive, patch, contraceptive vaginal ring, injectable progestogen, and implants\] or contraceptive subdermal implant or percutaneous contraceptive patches or intrauterine device \[IUD\] or intrauterine system \[IUS\]; vasectomy and tubal ligation or barrier method of birth control; female condom with spermicide, cervical cap, diaphragm with spermicide, contraceptive sponge), absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile \[at least 6 months prior to study drug administration\], during study and up to 32 days after the last dose of study drug.
• \*Postmenopausal defined as 12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age appropriate, \>45 years, in the absence of hormone replacement therapy).
• All male patients should avoid fathering a child by either true abstinence, hormonal or barrier method (e.g., male condom with diaphragm, male condom with cervical cap) or with their sexual partner the use of effective means of contraception throughout and till 92 days of administration of the last dose. They must not donate sperm for at least 92 days after the last dose of study drug.
• Ability to provide written informed consent and to be compliant with the schedule of protocol assessments. In case of illiterate patients, thumb impression of the patients will be obtained along with the signature of the impartial witness or legally authorized representative (LAR) on the consent form prior to patient's participation in the trial.Date of ALS 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., weakness. To be eligible for this study, the date of symptom onset must be no greater than exactly 9 months prior to the Screening Visit date.

You may not qualify if:

• With significant cognitive impairment, psychiatric disease, other neurodegenerative disorder (e.g., Parkinson disease or AD), substance abuse other causes of neuromuscular weakness, or any other condition that would make the participants unsuitable for participating in the study or could interfere with assessment or completing the study in the opinion of the Investigator.
• History of recent serious infection (e.g., pneumonia, septicemia) within 4 weeks of the screening visit; infection requiring hospitalization or treatment with IV antibiotics, antivirals, or antifungals within 4 weeks of screening; or chronic bacterial infection (such as tuberculosis) deemed unacceptable as per the Investigator's judgment
• With active herpes zoster infection within 2 months prior to the screening visit
• A documented history of attempted suicide within 6 months prior to the screening visit, or in the Investigator's judgment are at risk for a suicide attempt
• History of unstable or severe cardiac, pulmonary, oncological, hepatic, or renal disease or another medically significant illness other than ALS precluding their safe participation in this study
• Participants who are pregnant or are currently breastfeeding
• A known history of allergy to any ingredients of ZYIL1
• Patients taking concomitant medicines within 7 days or 5 half-lives of the medication (whichever is longer) prior to first dose of study drug administration till end of the study, which are substrate of CYP1A2 enzymes (e.g., alosetron, caffeine, duloxetine, melatonin, ramelteon, tasimelteon, tizanidine etc.) and CYP2B6 enzymes (e.g., bupropion, efavirenz etc.).
• 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 first dose of study drug administration.
• Use of any investigational drugs concurrently or within 4 weeks or 5 half-lives (whichever is longer), prior to first dose of study drug administration.
• Any clinically significant and/or laboratory significant value or other instability that would prevent the patient from participating in the study as determined by the Investigator.
• Received a live vaccine within 14 days before the screening visit or planning to receive during the study
• Participants who have received stem cell or gene therapy for ALS at any time in the past
• Any of the following laboratory values at screening
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3.0 × upper limit of normal (ULN)

Sponsors & Collaborators

• Zydus Lifesciences Limited: lead

Study Sites (7)

Zydus Hospitals & Healthcare Research

Ahmedabad, Gujarat, India

Location

Rhythm heart institute

Vadodara, Gujarat, India

Location

BrainS Super Speciality Hospital

Bengaluru, Karnataka, India

Location

KIMS-Kingsway Hospitals

Nagpur, Maharashtra, India

Location

Surya Multispecialty Hospital

Nashik, Maharashtra, 422003, India

Location

CIMET's Inamdar Multispeciality Hospital

Pune, Maharashtra, India

Location

Sir Ganga Ram Hospital

New Delhi, India

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

ZYIL1

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

• Dr. Deven Parmar, MD,FCP

  Zydus Therapeutics Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 8, 2023
• Study Start: November 9, 2023
• Primary Completion: June 26, 2024
• Study Completion: June 26, 2024
• Last Updated: December 19, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (7)