- Zydus Lifesciences Launches Phase II Clinical Trial of ZYIL1, an Innovative Oral Inhibitor of NLRP3 Inflammasome, for Patients with Amyotrophic Lateral Sclerosis
- The Phase 2 clinical trial will assess the safety and efficacy of ZYIL1 in Amyotrophic Lateral Sclerosis (ALS) patients [ClinicalTrials.gov ID: NCT05981040]
- ALS is a rare, progressive and fatal neurodegenerative disease, with an average life expectancy of 3 to 5 years from the time of symptom onset
Amyotrophic Lateral Sclerosis
Zydus Lifesciences, a global pharmaceutical company, has received approval from CDSCO, India, to conduct a Phase II clinical study of NLRP3 inhibitor “ZYIL1” in patients with Amyotrophic Lateral Sclerosis (ALS).
ALS is a disease that causes neuroinflammation and rapid neurodegeneration, leading to the loss of motor neurons in the brain and spinal cord, resulting in the inability to move, speak, eat, and breathe. The Phase II clinical trial will assess safety, tolerability, pharmacokinetics, and pharmacodynamics in ALS patients.
The trial’s primary endpoint is the placebo-controlled, randomized, double-blind Phase II clinical trial, which will measure the change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score at week 4, week 8, and week 12. Slow Vital Capacity (SVC), a predictor of functional loss in ALS, and neurofilament levels will also be evaluated at week 4 and week 12 as Key Secondary Endpoints. Zydus aims to improve the quality of life of patients through its life-changing discoveries, and this study is a positive step in that direction.
ZYIL1 is a small molecule NLRP3 inhibitor that is taken orally, and studies have shown that it is highly potent in suppressing inflammation caused by the NLRP3 inflammasome in human whole blood assays. In nonclinical studies, ZYIL1 was found to be distributed in the brain and cerebrospinal fluid of various species, including mice, rats, and non-human primates. The efficacy of ZYIL1 has been established in several validated pre-clinical models of neuroinflammation, Parkinson’s disease, Inflammatory Bowel Disease (IBD), and Multiple Sclerosis (MS). ZYIL1 has an acceptable ADME profile and a good safety margin, as demonstrated in Phase I studies [NCT04731324, NCT04972188].
Zydus has established the Phase 2 proof-of-concept in CAPS patients [NCT05186051] and has now published the data in Clinical Pharmacology in Drug Development. The USFDA has granted Zydus an ‘Orphan Drug Designation’ for ZYIL1 to treat patients with Cryopyrin Associated Periodic Syndrome (CAPS), a rare auto-inflammatory disease.
- ClinicalTrials.gov Identifier: NCT04972188 A Phase I, Prospective, Open Label, Multiple Dose Study of ZYIL1 Administered Via Oral Route to Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics In Healthy Adult Subjects
- ClinicalTrials.gov Identifier: NCT04731324 A Phase 1, Prospective Open Label, Single Dose, Single Arm Study of ZYIL1 Administered Via Oral Route to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Adult Human Subjects
- ClinicalTrials.gov Identifier: NCT05186051 A Phase 2a, Prospective, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS)
- Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Oral NLRP3 Inflammasome Inhibitor ZYIL1: First-in-human Phase 1 studies (Single Ascending Dose and Multiple Ascending Dose), Clinical Pharmacology in Drug Development, 2022. DOI: 10.1002/cpdd.1162
- Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Three Patients with Cryopyrin-Associated Periodic Syndromes, Clinical Pharmacology in Drug Development, 2023, 0(0) 1–8. DOI: 10.1002/cpdd.1318.