Safety and Tolerability, Pharmacokinetic and Pharmacodynamic Study With IZD334

Study Overview
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Brief Summary
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This is a first in human (FIH), single-centre, double -blind, randomised, cross-over, SAD followed by a MAD study of IZD334 conducted in healthy adult participants as well as an open-label cohort in adult patients with CAPS. The study is designed to evaluate the safety, tolerability, PK, PD, and food effect of IZD334 in healthy adult participants, and to evaluate the safety, tolerability, PK, PD, and preliminary clinical efficacy of IZD334 in adult patients with CAPS.

Official Title
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A Phase 1, Randomised, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Determine the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of IZD334 in Healthy Adult Participants as Well as an Open-label Cohort to Confirm the Safety, Pharmacokinetics, and Pharmacodynamics in Adult Patients With Cryopyrin-Associated Periodic Syndromes

Conditions
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Healthy Volunteers, Cryopyrin Associated Periodic Syndrome

Intervention / Treatment
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* Drug: IZD334
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (Healthy Volunteers) Healthy male or female volunteers, aged 18 to 65 years (inclusive at the time of informed consent) Participants must be in good general health, with no significant medical history, have no clinically significant abnormalities on physical examination at Screening and/or before administration of the initial dose of study drug Participants must have a Body Mass Index (BMI) between ≥18.0 and ≤32.0 kg/m2 at Screening Participants must have clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the Investigator or delegate Inclusion Criteria: (CAPS Patients) *Patients with a confirmed diagnosis of CAPS (FCAS or MWS) aged 18 to 65 years (inclusive at the time of informed consent) Exclusion Criteria: (Healthy volunteer) Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator's (or delegate's) opinion, could adversely affect the safety of the participant Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocol Blood donation or significant blood loss within 60 days prior to the first study drug administration Exclusion Criteria: (CAPS Patients) Live vaccinations within 3 months prior to Screening, for the duration of the study and for up to 3 months following the last dose of study drug; Positive QuantiFERON test at the Screening visit or within 2 months prior to Screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose<br>Once daily oral IZD334 or Placebo | Drug: IZD334<br>* Active Drug<br>Drug: Placebos<br>* Placebo to Match<br>|
| Experimental: Multiple Ascending Dose<br>Once or twice daily oral IZD334 or Placebo | Drug: IZD334<br>* Active Drug<br>Drug: Placebos<br>* Placebo to Match<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events [Safety and Tolerability] | Incidence, frequency and severity of treatment emergent adverse events. | Day 1-8 for SAD | 
| Incidence of treatment emergent adverse events [Safety and Tolerability] | Incidence, frequency and severity of treatment emergent adverse events. | Day 1-16 for MAD | 
| Peak plasma concentration (Cmax) single dose | Peak plasma concentration following single dose administration | Day 1-3 | 
| Area under the plasma concentration versus time curve (AUC)- single dose | AUC following single dose administration | Day 1-3 | 
| Peak Plasma Concentration (Cmax)-multiple dose | Peak plasma concentration following multiple dose administration | Days 1-9 | 
| Area under the plasma concentration versus time curve (AUC)- multiple dose | AUC following multiple dose administration | Days 1-9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of IL-1 production in stimulated whole blood | % reduction in IL-1 production in stimulated whole blood as measured by ELISA | Day 1-3 for SAD and Day 1-9 for MAD] | 
| Reduction in CAPS symptom scores | Reduction in Physician Assessed CAPS scores based on 8 point questionnaire | Day 1-15 |