ZYIL1 is a novel oral selective NLRP3 inflammasome inhibitor which prevents NLRP3-induced ASC oligomerization, thus inhibiting NLRP3 inflammasome pathway. ZYIL1 is expected to show benefit in patients demonstrating cytokine, like IL1β flare, including those exhibiting cytokine storm related to COVID-19 and other viral inflammatory diseases.
It is an open label, study designed to evaluate safety, tolerability, pharmacokinetics (PK)
and pharmacodynamics (PD) following a single-oral dose administration of ZYIL1 to healthy
subjects aged between 18-55 years old (Both Inclusive).
It will be conducted in up to 7 cohorts of 6 subjects each. Each cohort will be enrolled
within a 28 day screening period to ensure subjects meet all the inclusion criteria and none
of the exclusion criteria. Subjects will be administered single oral dose of ZYIL1 on Day 1.
In this study each cohort containing six subjects will be given a single oral dose of ZYIL1
in ascending manner. Initially, up to 3 cohorts of 18 subjects will be enrolled and dosed.
Interim analysis will be done after completion of three cohorts and submitted to Central
Licensing Authority of India(CLA). Further cohorts (i.e. cohort S4 onwards) will be conducted
after obtaining approval of CLA.
This is the first administration of ZYIL1 in humans; therefore, study design adjustments may
be made based on emerging data from each dose cohort based on review of preliminary safety,
tolerability, and PK results.
Drug: ZYIL1 capsule
NLRP3 inflammasome inhibitor
Inclusion Criteria:
1. Healthy male or non-lactating non-pregnant female between 18 and 55 years of age at
the time of signing the informed consent form (ICF). (Both inclusive).
2. Body mass index of 18.5 to 30.0 kg/m2 (Both inclusive) with a body weight of 50 to 100
kg (Both inclusive).
3. Normal QTc interval at screening and Check In [QTcF ≤450 ms]
4. Male subjects must agree to use adequate contraception methods during the study and be
willing and able to continue contraception for 90 days after administration of study
treatment.
5. Capable of giving written informed consent, which includes compliance with the study
procedures, restrictions, and requirements listed in the protocol.
6. Subjects who, in the opinion of the Investigator, are healthy as determined by their
pre study medical history, clinical examination, 12-lead ECG and clinical laboratory
tests within the institutional normal range or judged as not clinically significant by
the Investigator, including the following parameters: hematology, serum biochemistry,
urinalysis, and serology
7. Female subjects with history of sterility or at least 1 year menopause or use of long
acting non hormonal contraceptive measures (e.g., intrauterine device) and be willing
and able to continue contraception for 90 days after administration of study
treatment.
Exclusion Criteria:
1. History or presence of alcoholism or drug abuse within the past 1 year.
2. Presence or history of any of the following disorders/disease within the past 3
months, that might have impact on the clinical trial as per the investigator
discretion: cardiovascular, cerebrovascular, dermatological, gastrointestinal,
gynecological, hematological, hepatic, malignancy, metabolic, musculoskeletal,
neurological, urological, psychiatric, renal, respiratory, venereal, any other major
disorders
3. History of clinically significant hypersensitivity, intolerance, or allergies, as
determined by the Investigator.
4. History of COVID-19 infection within 14 days or contact with a confirmed active
COVID-19 positive patient within 14 days; or positive COVID-19 test within 5 days of
Check-in. .
5. History or presence of smoking or consumption of tobacco/nicotine products within the
past 1 year.
6. Difficulty with donating blood.
7. Systolic blood pressure more than 140 mmHg or less than 100 mmHg or diastolic blood
pressure more than 90 mmHg or less than 60 mmHg.
8. Pulse rate less than 55/minute or more than 100/minute.
9. Any clinically significant laboratory or ECG findings during screening
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 recent illness (eg, fever) within 14 days of check-in
12. Volunteers who have participated in any drug research study within past 3 months.
13. Volunteers who have donated one unit (350 ml) of blood in the past 3 months.
14. Has used prescription drugs and other substances (eg, dietary or herbal supplements
such as St John's Wort) known to be either significant enzyme inducers or enzyme
inhibitors within 4 weeks of Day 1, 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 of Day 1.
15. Use of any over-the-counter (OTC), any prescription medications or alternative
tradition of medicine (herbal medicines, homoeopathy, Siddha, Unani, etc.) within the
15 days or 5 half-lives (whichever is longer), prior to receiving study drug that
might have impact on the clinical trial as per the investigator discretion.
16. A positive urine drugs of abuse test or positive alcohol test at check-in.
17. 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.
18. 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.
19. Inability to be venipunctured or tolerate venous puncture.
20. Any condition or abnormal baseline findings that in the 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.
21. Other unspecified reasons that, in the opinion of the Investigator or the Sponsor,
make the subject unsuitable for the study.
22. Female subjects who are pregnant, currently breastfeeding, or attempting to conceive.
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Zydus Research Centre
Ahmedabad, Gujarat, India
Dr Deven Parmar, MD, Study Chair
Cadila Healthcare Ltd.