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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05186051




Registration number
NCT05186051
Ethics application status
Date submitted
23/12/2021
Date registered
11/01/2022
Date last updated
11/07/2022

Titles & IDs
Public title
A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS)
Scientific title
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)
Secondary ID [1] 0 0
ZYIL1.21.001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cryopyrin Associated Periodic Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZYIL1 capsule

Experimental: ZYIL1 Capsule - subject will receive 50 mg twice daily (BD) dose for 7 days


Treatment: Drugs: ZYIL1 capsule
NLRP3 inflammasome inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and Severity of Adverse event of ZYIL1
Timepoint [1] 0 0
Baseline to Day 7
Secondary outcome [1] 0 0
Maximum concentration (Cmax)
Timepoint [1] 0 0
Pre-dose to Day 7
Secondary outcome [2] 0 0
To evaluate disease activity scores based on 5 point physician and patient global assessment over 7 days treatment of ZYIL1
Timepoint [2] 0 0
Baseline to Day 10
Secondary outcome [3] 0 0
Time to reach maximum concentration (Tmax)
Timepoint [3] 0 0
Pre-dose to Day 7
Secondary outcome [4] 0 0
Area under the curve for dosing interval(12 hours) AUCtau
Timepoint [4] 0 0
Pre-dose to Day 7
Secondary outcome [5] 0 0
Change in WBC count
Timepoint [5] 0 0
Baseline to Day 10
Secondary outcome [6] 0 0
Change in IL-1ß
Timepoint [6] 0 0
Baseline to Day 10
Secondary outcome [7] 0 0
Change in Serum amyloid protein A
Timepoint [7] 0 0
Baseline to Day 10
Secondary outcome [8] 0 0
Change in IL-6
Timepoint [8] 0 0
Baseline to Day 10
Secondary outcome [9] 0 0
Change in CRP
Timepoint [9] 0 0
Baseline to Day 10

Eligibility
Key inclusion criteria
1. 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:

1. 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

2. Documented verification of a genetic mutation in NLRP3.

2. Positive response of ZYIL1 in inhibiting secreted IL-1ß from peripheral blood
mononuclear cells isolated from the subject's blood treated with LPS ex vivo showing
half maximal inhibitory concentration below 500 nM.

3. Subject must be willing to discontinue current anti-IL-1 treatment prior to study drug
dosing if applicable.

4. 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]).

5. Subject must have a body mass index (BMI) between =18.0 and =38.0 kg/m2 at Screening.

6. 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.

7. 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.

2. 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).

3. Any clinically significant laboratory or ECG findings during the screening in the
opinion of the Investigator.

4. Estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2, as measured by the
Cockcroft-Gault equation at screening

5. Total bilirubin above upper limit of normal (ULN) or AST(SGOT)/ALT(SGPT) > 1.5 times
of ULN at screening

6. QT interval corrected for heart rate using Fridericia's method (QTcF) > 450 msec at
screening

7. History of clinically significant hypersensitivity, intolerance, or allergies, as
determined by the investigator.

8. History of fever, cough or any other active systemic infections within 2 weeks prior
to receiving study drug.

9. 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

10. 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).

11. Subjects who have donated one unit (490 mL) of blood in the past 3 months.

12. 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.

13. 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

14. 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.

15. Female subjects who are pregnant, currently breastfeeding, or attempting to conceive.

16. Any disorder that, in the Investigator's opinion, may interfere with study compliance,
such as significant mental, nervous disorder or other illness. In making this
assessment, the Investigator must refer to the study information provided including
the Investigator's Brochure.

17. Inability to be venipuncture or tolerate venous puncture.

18. Any condition or abnormal baseline findings that in investigator's judgment might
increase the risk to the subject or decrease the chance of obtaining satisfactory data
needed to obtain the objective of the study.

19. Other unspecified reasons that, in the opinion of the investigator make the subject
unsuitable for the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/07/2022
Sample size
Target
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Department of Clinical Immunology and Allergy - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Zydus Lifesciences Limited
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05186051
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dr Deven Parmar, MD
Address 0 0
Cadila Healthcare Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries