Safety and Tolerability, Pharmacokinetic and Pharmacodynamic Study With IZD334

• ClinicalTrials.gov Identifier: NCT04086602
• Recruitment Status: Completed
• First Posted: September 11, 2019
• Last Update Posted: March 2, 2020
• Sponsor: Inflazome UK Ltd
• Information provided by (Responsible Party): Inflazome UK Ltd

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers; Cryopyrin Associated Periodic Syndrome	Drug: IZD334; Drug: Placebos	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Healthy volunteer section is double blind.
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: September 13, 2019
• Actual Primary Completion Date: February 4, 2020
• Actual Study Completion Date: February 4, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Australia, Victoria

Nucleus Network

Melbourne, Victoria, Australia

Sponsors and Collaborators

Inflazome UK Ltd

Investigators

• Principal Investigator: Jason Lickliter, MBBS, PhD; Nucleus Network

More Information

• Responsible Party: Inflazome UK Ltd
• ClinicalTrials.gov Identifier: NCT04086602
• Other Study ID Numbers: IZD334-001
• First Posted: September 11, 2019
• Last Update Posted: March 2, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cryopyrin-Associated Periodic Syndromes; Syndrome; Disease; Pathologic Processes; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases