A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS)

NCT05186051 | Completed Phase 2

• 1 other identifier: ZYIL1.21.001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

ZYIL1 is expected to show benefit in patients with CAPS. The present study aims to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of ZYIL1 when administered to subjects with CAPS.

Conditions

Cryopyrin Associated Periodic Syndrome

Keywords

NLRP3; NLPR3 Inflammasone inhibitor

Outcome Measures

Primary Outcomes (1)

• Incidence and Severity of Adverse event of ZYIL1

  The Common Terminology Criteria for Adverse Event (CTCAE) (Version 5.0 or higher) system will be used for reporting and grading

  Baseline to Day 7

Secondary Outcomes (9)

• Maximum concentration (Cmax)

  Pre-dose to Day 7

• To evaluate disease activity scores based on 5 point physician and patient global assessment over 7 days treatment of ZYIL1

  Baseline to Day 10

• Time to reach maximum concentration (Tmax)

  Pre-dose to Day 7

• Area under the curve for dosing interval(12 hours) AUCtau

  Pre-dose to Day 7

• Change in WBC count

  Baseline to Day 10

Study Arms (1)

ZYIL1 Capsule

EXPERIMENTAL

subject will receive 50 mg twice daily (BD) dose for 7 days

Drug: ZYIL1 capsule

Interventions

ZYIL1 capsule DRUG

NLRP3 inflammasome inhibitor

ZYIL1 Capsule

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with a confirmed diagnosis of CAPS (FCAS, NOMID, or MWS) aged 18 to 75 years inclusive at screening A confirmed diagnosis of CAPS comprises the following:
• Subject has previously experienced at least 2 typical clinical symptoms of CAPS (may include urticarial skin rash, myalgia, arthralgia, recurrent fever, fatigue/malaise, headache, conjunctivitis, and any other autoinflammatory symptom); and
• Documented verification of a genetic mutation in NLRP3.
• Positive response of ZYIL1 in inhibiting secreted IL-1β from peripheral blood mononuclear cells isolated from the subject's blood treated with LPS ex vivo showing half maximal inhibitory concentration below 500 nM.
• Subject must be willing to discontinue current anti-IL-1 treatment prior to study drug dosing if applicable.
• Subject must demonstrate flaring of CAPS de novo or after discontinuation of anti-IL-1 inhibitor treatment. Flaring is defined as worsening of disease activity as per physician global assessment of disease activity with elevation of CRP (\>2 x upper limit of normal \[ULN\]).
• Subject must have a body mass index (BMI) between ≥18.0 and ≤38.0 kg/m2 at Screening.
• Female subject of reproductive age must be non-pregnant and non-lactating, and must use an acceptable, highly effective contraception from screening until 1 month after the last dose of study drug.
• Male subject must be willing to use contraception and must not donate sperm for at least 90 days after the last dose of study drug.

You may not qualify if:

• Any severe, progressive, or uncontrolled medical condition within the past 3 months that might have impact on the clinical trial as per the investigator's discretion.
• Use of any investigational drug or investigational medical device or participation in other clinical study within 4 weeks prior to Screening or 5 half- lives of the product (whichever is longer).
• Any clinically significant laboratory or ECG findings during the screening in the opinion of the Investigator.
• Estimated glomerular filtration rate (eGFR) \< 90 mL/min/1.73m2, as measured by the Cockcroft-Gault equation at screening
• Total bilirubin above upper limit of normal (ULN) or AST(SGOT)/ALT(SGPT) \> 1.5 times of ULN at screening
• QT interval corrected for heart rate using Fridericia's method (QTcF) \> 450 msec at screening
• History of clinically significant hypersensitivity, intolerance, or allergies, as determined by the investigator.
• History of fever, cough or any other active systemic infections within 2 weeks prior to receiving study drug.
• History or presence of alcohol abuse (alcohol consumption more than 40 g/4 units/4standard drinks per day), or drug habituation, or any prior intravenous usage of an illicit substance
• 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).
• Subjects who have donated one unit (490 mL) of blood in the past 3 months.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes including St John's Wort within 4 weeks prior to receiving study drug 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, or use of grapefruit or similar substances (Seville oranges or marmalade, grapefruit juice, grapefruit hybrids, pomelos, exotic citrus fruits or fruit juices) within 7 days prior to the Run-in period.
• Use or intend to use any over-the-counter (vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) or prescription medications within 7 days or 5 half-lives (whichever is longer) prior to receiving study drug, with the exception of hormone replacement therapy and therapies for chronic stable diseases that have been stable for at least 30 days prior to screening and until Day 1, unless deemed acceptable by the investigator
• History of or positive screening test for hepatitis C infection (defined as positive for hepatitis C virus antibody), hepatitis B infection (defined as positive for hepatitis B surface antigen), or human immunodeficiency virus I or II.
• Female subjects who are pregnant, currently breastfeeding, or attempting to conceive.

Sponsors & Collaborators

• Zydus Lifesciences Limited: lead

Study Sites (1)

Department of Clinical Immunology and Allergy

Adelaide, 5000, Australia

Location

MeSH Terms

Conditions

Cryopyrin-Associated Periodic Syndromes

Interventions

ZYIL1

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Inducible Urticaria; Chronic Urticaria; Urticaria; Skin Diseases, Vascular; Cold Urticaria; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dr Deven Parmar, MD

  Cadila Healthcare Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2021
• First Posted: January 11, 2022
• Study Start: June 1, 2022
• Primary Completion: July 2, 2022
• Study Completion: July 2, 2022
• Last Updated: July 11, 2022

Record last verified: 2021-12

Locations

AU (1)