Safety and Tolerability, Pharmacokinetic and Pharmacodynamic Study With IZD334

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Cryopyrin Associated Periodic Syndrome
• Intervention / Treatment: Drug: IZD334; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Ascending Dose; Once daily oral IZD334 or Placebo	Drug: IZD334; Active Drug; Drug: Placebos; Placebo to Match
EXPERIMENTAL: Multiple Ascending Dose; Once or twice daily oral IZD334 or Placebo	Drug: IZD334; Active Drug; Drug: Placebos; Placebo to Match

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Inflazome UK Ltd
• Investigators: Principal Investigator: Jason Lickliter, MBBS, PhD, Nucleus Network

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 13, 2019
• Primary Completion (ACTUAL): February 4, 2020
• Study Completion (ACTUAL): February 4, 2020

Study Registration Dates

• First Submitted: September 9, 2019
• First Submitted That Met QC Criteria: September 10, 2019
• First Posted (ACTUAL): September 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 2, 2020
• Last Update Submitted That Met QC Criteria: February 27, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Disease; Genetic Diseases, Inborn; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Syndrome; Cryopyrin-Associated Periodic Syndromes
• Other Study ID Numbers: IZD334-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No