Safety and PK of Repeated Doses of IRL201104 in Healthy Volunteers

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: IRL201104; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Hammersmith Medicines Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1: Dose A IRL201104 or placebo; IRL201104 IV once daily for 5 days OR Placebo IV once daily for 5 days	Drug: IRL201104; lyophilised powder for reconstitution for IV dosing; Drug: Placebo; Matching placebo for IRL201104
EXPERIMENTAL: Group 2: Dose B IRL201104 or placebo; IRL201104 IV once daily for 7 days OR Placebo IV once daily for 7 days	Drug: IRL201104; lyophilised powder for reconstitution for IV dosing; Drug: Placebo; Matching placebo for IRL201104

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Revolo Biotherapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 29, 2021
• Primary Completion (ACTUAL): April 5, 2021
• Study Completion (ACTUAL): April 5, 2021

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (ACTUAL): February 10, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2021
• Last Update Submitted That Met QC Criteria: April 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: C1104-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No