SAD Study of APR002 Investigating the Safety/Tolerability, Pharmacokinetics/Pharmacodynamics in Healthy Subjects

Study Overview
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Brief Summary
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This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of APR002 in healthy subjects.

Detailed Description
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A Phase 1, Randomized, Blinded, Placebo-Controlled, First-in-Human, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of APR002 Administered by Inhalation in Healthy Volunteers

Official Title
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A Phase 1, Randomized, Blinded, Placebo-Controlled, First-in-Human, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of APR002 Administered by Inhalation in Healthy Volunteers

Conditions
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COVID-19

Intervention / Treatment
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* Drug: APR002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men or women aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture. Women can be of childbearing potential and must have been stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 (screening) and be willing to continue on the chosen contraceptive method Male subjects should be willing to use a condom (with spermicide) to prevent pregnancy and drug exposure of a female partner and refrain from donating sperm or fathering a child from the day of the investigational product administration until 3 months Have a body mass index (BMI) between 18 and 32 kg/m2 and weigh at least 45 kg. Exclusion Criteria: History or presence of clinically significant medical (e.g., chronic obstructive pulmonary disease, asthma, COVID-19, etc.) or psychiatric condition or disease Abnormal vital signs, after minutes rest, defined as any of the following (SBP > 140 mmHg, Diastolic blood pressure (DBP) > 90 mmHg, Heart rate < 40 or > 99 beats per minute) Prolonged QTcF > 450 ms or family history of long QT syndrome

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention/Treatment<br>Single dose, oral inhalation (nebuliser solution) | Drug: APR002<br>* Active Investigational Product<br>* Other names: TLR7 agonist;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>* Other names: 0.9% Sodium Chloride; Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of APR002 in healthy subjects as assessed by incidence of treatment-emergent adverse events according to CTCAE v5.0 criteria | Safety assessments will include evaluation of incidence of treatment-emergent adverse events (AEs) according to CTCAE v5.0 criteria, including vital signs, resting electrocardiogram (ECG) parameters, standard hematology, chemistry, urinalysis and other tests | Screening up to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of APR002 in healthy subjects as assessed by maximum plasma concentration (Cmax) towards determination of the optimal pharmacokinetic dose | Determination of maximum plasma concentration (Cmax) | Day 1 to Day 3 | 
| Pharmacokinetics of APR002 in healthy subjects as assessed by time to maximum concentration (Tmax) towards determination of the optimal pharmacokinetic dose | Determination of time to maximum concentration | Day 1 to Day 3 | 
| Pharmacokinetics of APR002 in healthy subjects as assessed by plasma exposure (AUC0-t, AUC0-inf) determination of the optimal pharmacokinetic dose | Determination of plasma exposure (AUC0-t, AUC0-inf) | Day 1 to Day 3 | 
| Pharmacokinetics of APR002 in healthy subjects as assessed by terminal elimination half life (t1/2) determination of the optimal pharmacokinetic dose | Determination of terminal half life | Day 1 to Day 3 | 
| Pharmacokinetics of APR002 in healthy subjects as assessed by apparent volume of distribution during the terminal elimination phase after inhalation (extravascular) administration for determination of the optimal pharmacokinetic dose | Determination of volume of distribution (CL/F and Vz/F) | Day 1 to Day 3 |