Safety and Tolerability, Pharmacokinetic and Pharmacodynamic Study With Inzomelid

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 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.

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 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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Inzomelid
* Drug: Placebo


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; 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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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>Inzomelid or Placebo | Drug: Inzomelid<br>* Active Drug<br>Drug: Placebo<br>* Placebo to Match<br>|
| Experimental: Multiple Ascending Dose<br>Inzomelid or Placebo | Drug: Inzomelid<br>* Active Drug<br>Drug: Placebo<br>* Placebo to Match<br>|
| Experimental: Patients with CAPS<br>Inzomelid Open Label | Drug: Inzomelid<br>* Active Drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 |