Safety and Tolerability, Pharmacokinetic and Pharmacodynamic Study With Inzomelid

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 Inzomelid in Healthy Adult Participants as Well as an Open Label Cohort to Confirm the Safety, Pharmacokinetics, and Pharmacodynamics of Inzomelid 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 Inzomelid. The study is designed to evaluate the safety, tolerability, PK, PD, and food effect of Inzomelid in healthy adult participants and to evaluate the safety, tolerability, PK, PD, and preliminary clinical efficacy of Inzomelid in adult patients with CAPS. Oversight will be provided by a safety monitoring committee (SMC) comprised of the Investigator, the Sponsor's Medical Monitor and an Independent Medical Monitor.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Inzomelid; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Melbourne, Queensland, Australia
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 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;

Inclusion Criteria- CAPS Patients:

* Patients with a confirmed diagnosis of CAPS (FCAS, NOMID, or MWS) aged 18 to 70 years (inclusive at the time of informed consent);

Exclusion Criteria- Healthy Volunteers:

• 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;

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.

Participants who have a positive QuantiFERON test with documentation of BCG vaccination, who are at low environmental risk for TB infection or reactivation, and have a negative chest X-ray can be included;

* Pregnant or lactating at Screening or planning to becomepregnant (self or partner) at any time during the study, including the follow-up period;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Ascending Dose; Inzomelid or Placebo	Drug: Inzomelid; Active Drug; Drug: Placebo; Placebo to Match
EXPERIMENTAL: Multiple Ascending Dose; Inzomelid or Placebo	Drug: Inzomelid; Active Drug; Drug: Placebo; Placebo to Match
EXPERIMENTAL: Patients with CAPS; Inzomelid Open Label	Drug: Inzomelid; Active Drug

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic activity	NLRP3 Inhibition in whole blood	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	Days 1-15

Collaborators and Investigators

• Sponsor: Inflazome UK Ltd
• Investigators: Principal Investigator: Ben Snyder, MB, BS, Nucleus Network

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 16, 2019
• Primary Completion (ACTUAL): March 23, 2020
• Study Completion (ACTUAL): March 23, 2020

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 9, 2019
• First Posted (ACTUAL): July 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: IZD174-001

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