Safety and Tolerability, Pharmacokinetic and Pharmacodynamic Study With Inzomelid

• ClinicalTrials.gov Identifier: NCT04015076
• Recruitment Status: Completed
• First Posted: July 10, 2019
• Last Update Posted: March 27, 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 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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Inzomelid; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• 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 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
• Actual Study Start Date: July 16, 2019
• Actual Primary Completion Date: March 23, 2020
• Actual Study Completion Date: March 23, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Pharmacodynamic activity [ Time Frame: Day 1-3 for SAD and Day 1-9 for MAD ]
   NLRP3 Inhibition in whole blood
2. Reduction in CAPS symptom scores [ Time Frame: Days 1-15 ]
   Reduction in Physician Assessed CAPS scores based on 8 point questionnaire

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 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;

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;

Contacts and Locations

Locations

Australia, Queensland

Nucleus Network

Melbourne, Queensland, Australia

Sponsors and Collaborators

Inflazome UK Ltd

Investigators

• Principal Investigator: Ben Snyder, MB, BS; Nucleus Network

More Information

• Responsible Party: Inflazome UK Ltd
• ClinicalTrials.gov Identifier: NCT04015076
• Other Study ID Numbers: IZD174-001
• First Posted: July 10, 2019
• Last Update Posted: March 27, 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