Cryopyrin Associated Periodic SyndromePhase 2NCT05186051
A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS)
A Phase 2 study testing ZYIL1 capsule in people with Cryopyrin Associated Periodic Syndrome, run by Zydus Lifesciences Limited at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cryopyrin Associated Periodic Syndrome
- What is being tested?
- ZYIL1 capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteAustralia
- Study dates
- 1 Jun 2022to 2 Jul 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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]).
Show all 9Show fewer
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Australia1 site
Department of Clinical Immunology and Allergy
Adelaide, 5000
About this study
Official 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)
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.
Read the 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.
- Conditions
- Cryopyrin Associated Periodic Syndrome
- Being tested
- ZYIL1 capsule
- Keywords
- NLRP3, NLPR3 Inflammasone inhibitor
- Medical subject headings
- Cryopyrin-Associated Periodic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZYIL1 capsuleDrug
NLRP3 inflammasome inhibitor
| Study group | Role | What they receive |
|---|---|---|
| ZYIL1 Capsule | Experimental | subject will receive 50 mg twice daily (BD) dose for 7 days Receives: Drug: ZYIL1 capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline to Day 7
Secondary outcomes (9)
Maximum concentration (Cmax)
Blood samples will be withdrawn on Day 1 and Day 7 to evaluate maximum concentration
Measured: 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
Physician global assessment on 5 point scale score will be taken
Measured: Baseline to Day 10
Time to reach maximum concentration (Tmax)
Blood samples will be withdrawn on Day 1 and Day 7 to evaluate Time to reach maximum concentration
Measured: Pre-dose to Day 7
Area under the curve for dosing interval(12 hours) AUCtau
Blood samples will be withdrawn on Day 1 and Day 7 to evaluate AUCtau
Measured: Pre-dose to Day 7
Change in WBC count
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
Measured: Baseline to Day 10
Change in IL-1β
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
Measured: Baseline to Day 10
Change in Serum amyloid protein A
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
Measured: Baseline to Day 10
Change in IL-6
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
Measured: Baseline to Day 10
Change in CRP
Blood samples will be collected from pre-dose till Day 10 to evaluate the change
Measured: Baseline to Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start1 Jun 2022
- Primary completion2 Jul 2022
- Study completion2 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cryopyrin Associated Periodic SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zydus Lifesciences Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr Deven Parmar, MD, Study director, Cadila Healthcare Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05186051
- Sponsor's protocol ID
- ZYIL1.21.001
- Status last verified
- Dec 2021
- First submitted
- 23 Dec 2021
- Last updated
- 11 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT05186051
- Acronym / sponsor ID
- ZYIL1.21.001
- Conditions
- Cryopyrin Associated Periodic Syndrome
- Keywords
- NLRP3, NLPR3 Inflammasone inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Zydus Lifesciences LimitedIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 2 Jul 2022 (actual)
- Study completion
- 2 Jul 2022 (actual)
- First posted
- 11 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ZYIL1 Capsule | Experimental | Drug: ZYIL1 capsulesubject will receive 50 mg twice daily (BD) dose for 7 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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.
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZYIL1 capsuleNLRP3 inflammasome inhibitor | Drug | ZYIL1 Capsule |
Primary outcome
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
9 secondary outcomes
Maximum concentration (Cmax)
Time frame: 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
Time to reach maximum concentration (Tmax)
Time frame: Pre-dose to Day 7
Area under the curve for dosing interval(12 hours) AUCtau
Time frame: Pre-dose to Day 7
Change in WBC count
Time frame: Baseline to Day 10
Change in IL-1β
Time frame: Baseline to Day 10
Change in Serum amyloid protein A
Time frame: Baseline to Day 10
Change in IL-6
Time frame: Baseline to Day 10
Change in CRP
Time frame: Baseline to Day 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2022.
Related trials for Cryopyrin Associated Periodic Syndrome
RecruitingObservational study
Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
NOMID, DIRA
RecruitingPhase 1
Repeat PET/CT Imaging in People With CAPS and Anakinra-Induced Amyloidosis Using an Amyloid-Reactive Peptide to Measure Changes in Organ-Specific Amyloid Load
Cryopyrin-Associated Periodic Syndromes, Amyloidosis
RecruitingObservational study
Ilaris NIS in Korea
Hereditary Periodic Fever Syndromes, Cryopyrin-associated Periodic Syndromes (CAPS)
Recruiting
Circadian Rhythm Deregulation in Patients With CAPS
Cryopyrin Associated Periodic Syndrome, Familial Cold Urticaria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Deven Parmar, MD study director
Cadila Healthcare Ltd.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ZYIL1 capsule in people with Cryopyrin Associated Periodic Syndrome, run by Zydus Lifesciences Limited at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and Severity of Adverse event of ZYIL1 (time frame: Baseline to Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2022.