- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05186051
A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS)
July 8, 2022 updated by: Zydus Lifesciences Limited
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)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is a phase 2a, prospective, open-label study.
Primary objective of the study is to determine safety and tolerability profile of twice daily oral administration of ZYIL1 administered for 7 days.
The study will be conducted in 3 subjects having CAPS as per eligibility criteria.
The study will be divided in three periods: Screening Period; Run-in Period and Study Period.
Study Type
Interventional
Enrollment (Actual)
3
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Adelaide, Australia, 5000
- Department of Clinical Immunology and Allergy
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
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.
Exclusion Criteria:
- 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.
- 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.
- Inability to be venipuncture or tolerate venous puncture.
- 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.
- Other unspecified reasons that, in the opinion of the investigator make the subject unsuitable for the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ZYIL1 Capsule
subject will receive 50 mg twice daily (BD) dose for 7 days
|
NLRP3 inflammasome inhibitor
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence and Severity of Adverse event of ZYIL1
Time Frame: Baseline to Day 7
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum concentration (Cmax)
Time Frame: Pre-dose to Day 7
|
Blood samples will be withdrawn on Day 1 and Day 7 to evaluate maximum concentration
|
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
Time Frame: Baseline to Day 10
|
Physician global assessment on 5 point scale score will be taken
|
Baseline to Day 10
|
Time to reach maximum concentration (Tmax)
Time Frame: Pre-dose to Day 7
|
Blood samples will be withdrawn on Day 1 and Day 7 to evaluate Time to reach maximum concentration
|
Pre-dose to Day 7
|
Area under the curve for dosing interval(12 hours) AUCtau
Time Frame: Pre-dose to Day 7
|
Blood samples will be withdrawn on Day 1 and Day 7 to evaluate AUCtau
|
Pre-dose to Day 7
|
Change in WBC count
Time Frame: Baseline to Day 10
|
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
|
Baseline to Day 10
|
Change in IL-1β
Time Frame: Baseline to Day 10
|
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
|
Baseline to Day 10
|
Change in Serum amyloid protein A
Time Frame: Baseline to Day 10
|
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
|
Baseline to Day 10
|
Change in IL-6
Time Frame: Baseline to Day 10
|
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
|
Baseline to Day 10
|
Change in CRP
Time Frame: Baseline to Day 10
|
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
|
Baseline to Day 10
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Dr Deven Parmar, MD, Cadila Healthcare Ltd.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2022
Primary Completion (Actual)
July 2, 2022
Study Completion (Actual)
July 2, 2022
Study Registration Dates
First Submitted
December 23, 2021
First Submitted That Met QC Criteria
December 23, 2021
First Posted (Actual)
January 11, 2022
Study Record Updates
Last Update Posted (Actual)
July 11, 2022
Last Update Submitted That Met QC Criteria
July 8, 2022
Last Verified
December 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ZYIL1.21.001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cryopyrin Associated Periodic Syndrome
-
Inflazome UK LtdCompletedHealthy Volunteers | Cryopyrin Associated Periodic SyndromeAustralia
-
Novartis PharmaceuticalsCompletedCryopyrin Associated Periodic SyndromeCanada
-
University Hospital, LilleCompleted
-
Assistance Publique - Hôpitaux de ParisInstitut ImagineNot yet recruitingAutoinflammatory Disease | FMF | TRAPS | MKD | Cryopyrin Associated Periodic Syndrome | HaploinsufficiencyFrance
-
Aclaris Therapeutics, Inc.TerminatedCryopyrin-Associated Periodic SyndromeUnited States
-
Handok Inc.Terminated
-
Zomagen Biosciences, LtdCompletedCryopyrin Associated Periodic SyndromeUnited States
-
Novartis PharmaceuticalsCompletedCryopyrin-associated Periodic Syndromes (CAPS) | Familial Cold Autoinflam Syn (FCAS) | Muckle-wells Syn (MWS) | Neonatal Onset Multisystem Inflam Disease (NOMID)Switzerland, United States, Germany, Norway, Austria
-
Peking Union Medical College HospitalRecruitingCryopyrin-Associated Periodic SyndromesChina
-
Swedish Orphan BiovitrumPediatric Rheumatology International Trials OrganizationCompletedCryopyrin-Associated Periodic SyndromesUnited Kingdom, Netherlands
Clinical Trials on ZYIL1 capsule
-
Zydus Lifesciences LimitedCompleted
-
Zydus Lifesciences LimitedCompleted
-
Zydus Lifesciences LimitedRecruitingAmyotrophic Lateral SclerosisIndia
-
Quan JiangUnknown
-
Guizhou Bailing Group Pharmaceutical Co LtdWangjing Hospital, China Academy of Chinese Medical Sciences; The First Affiliated... and other collaboratorsUnknownKnee OsteoarthritisChina
-
Jonsson Comprehensive Cancer CenterWithdrawnAcute Graft Versus Host Disease | Gastrointestinal Tract Acute Graft Versus Host Disease | Severe Gastrointestinal Tract Acute Graft Versus Host Disease | Steroid Resistant Gastrointestinal Tract Acute Graft Versus Host DiseaseUnited States
-
Yung Shin Pharm. Ind. Co., Ltd.Changhua Christian HospitalCompletedHot Flashes | PMSTaiwan
-
Chipscreen Biosciences, Ltd.Not yet recruiting
-
Burapha UniversityCompletedAsparagus Capsule ConsumptionThailand
-
Vibrant Ltd.CompletedConstipationUnited States