Safety and PK of Repeated Doses of IRL201104 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and pharmacokinetics of repeat doses of IRL201104 given to healthy volunteers.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Parallel Group Study in Healthy Volunteers to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of IRL201104 to Support a Future COVID-19 Patient Study

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: IRL201104
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects age 18 to 65 years of age, and in good health as determined by medical history, physical examination, vital signs, electrocardiogram, and laboratory tests. Female subjects agree to use highly effective contraception or be of non-childbearing potential. Written informed consent must be obtained before any assessment is performed. Able to communicate well with the Investigator/designee. Exclusion Criteria: Any known reaction to study drug or components concurrent or recent infection or clinically significant conditions that may place subject at risk or interference with absorption, distribution or excretion of drugs No QTcF interval ≥450 milliseconds, no QRS complex ≥120 milliseconds, at Screening Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or human immunodeficiency virus (HIV) 1 and/or -2 antibodies at Screening. Excessive use of caffeine-containing beverages Urinary cotinine level indicative of smoking or history or regular use of tobacco- or nicotine containing products within 6 months before screening. Presence or history of drug of alcohol abuse. Positive screen for drugs-of-abuse or cotinine. Blood donation in excess of 500mL within 3 months. Participation in another clinical study with licensed or unlicensed study drug within 3 months of first IMP administration. Exposure to more than 4 new chemical entities within 12 months before the first IMP administration. Use of live vaccine 28 days before dosing with study drug until telephone follow-up and use of killed vaccine (including COVID-19 vaccine) 14 days before dosing with study drug until telephone follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Dose A IRL201104 or placebo<br>IRL201104 IV once daily for 5 days OR Placebo IV once daily for 5 days | Drug: IRL201104<br>* lyophilised powder for reconstitution for IV dosing<br>Drug: Placebo<br>* Matching placebo for IRL201104<br>|
| Experimental: Group 2: Dose B IRL201104 or placebo<br>IRL201104 IV once daily for 7 days OR Placebo IV once daily for 7 days | Drug: IRL201104<br>* lyophilised powder for reconstitution for IV dosing<br>Drug: Placebo<br>* Matching placebo for IRL201104<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with TEAEs and number of events will be summarised by treatment | Adverse Events after treatment administration will be collected at baseline and repeated until study completion | 33 (group 1) or 35 (group 2) days | 
| Number of subjects with potentially clinically important (PCI) abnormal haematology variables will be summarised by treatment | Haemoglobin, haematocrit, MCV, MCH, MCHC, RBC, WBC and differentials will be collected at baseline and after dose administration and repeated until Day 19 or 21 | 19 (group 1) or 21 (group 2) days | 
| Number of subjects with PCI abnormal clinical chemistry variables will be summarised by treatment | Creatinine, glucose, triglycerides, urea, uric acid, bilirubin, cholesterol, sodium, potassium, alkaline phosphatase, AST, ALT and GGT will be collected at baseline and after dose administration and repeated until Day 19 or 21 | 19 (group 1) or 21 (group 2) days | 
| Number of subjects with PCI and/or abnormal electrocardiogram variables will be summarised by treatment | RR, PR, QRS, QT-interval, QTcF and heart rate will be collected at baseline and after dose administration and repeated until Day 19 or 21. | 19 (group 1) or 21 (group 2) days | 
| Number of subjects with PCI abnormal vital sign variables will be summarised by treatment | Blood pressure, pulse rate, oral body temperature and respiration rate will be collected at baseline and after single and multiple dose administration and repeated until Day 19 or 21 | 19 (group 1) or 21 (group 2) days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of IRL201104: Trough blood concentration (Ctrough) | Ctrough will be measured after multiple dosing | 5 (group 1) or 7 (group 2) days | 
| PK of IRL201104: Maximum (peak) blood concentration (Cmax) | Cmax will be calculated after multiple dosing | 5 (group 1) or 7 (group 2) days | 
| PK of IRL201104: Terminal half life (t1/2) | t1/2 will be calculated after multiple dosing | 5 (group 1) or 7 (group 2) days | 
| PK of IRL201104: Area under the curve from time zero to last quantifiable concentration of IRL201104 (AUCt) | AUCt will be calculated after multiple dosing | 5 (group 1) or 7 (group 2) days | 
| PK of IRL201104: Apparent total body clearance from blood (CLss) | CLss will be calculated after multiple dosing | 5 (group 1) or 7 (group 2) days | 
| PK of IRL201104: steady state volume of distribution (Vz) | Vz will be calculated after multiple dosing | 5 (group 1) or 7 (group 2) days |