| Eligibility |
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.
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.
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