A First in Human Study of AX-202 in Healthy Subjects and Patients With Psoriasis.

Study Overview
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Brief Summary
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The first-in-human study will be performed in healthy volunteers and patients with a chronic inflammatory skin disease. The primary objective is to evaluate the safety, tolerability and pharmacokinetics of increasing doses of AX-202 infusion.

Official Title
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A First-in-human, Randomised Double-blind, Placebo-controlled 2-part Study to Evaluate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Single Ascending Doses of AX-202 in Healthy Subjects and Multiple Ascending Doses of AX-202 in Patients With Mild to Moderate Chronic Plaque Psoriasis.

Conditions
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Healthy Volunteers, Mild to Moderate Psoriasis

Intervention / Treatment
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* Biological: Placebo
* Biological: AX-202


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Part A / Single ascending doses: Male and female subjects must be between 18-55 years inclusive, at the time of informed consent. Subjects must have a Body Mass Index (BMI) ≥ 18 and ≤ 32 kg/m2 and weight of at least 45kg at screening. Subjects must be in good health as determined by medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory assessments at the time of screening, as judged by the Investigator. Part B / Multiple ascending doses: Male and female patients must be between 18-65 years inclusive, at the time of informed consent. Patients must have a documented diagnosis of plaque psoriasis for ≥ 6 months prior to screening. Patients must have a Body Mass Index (BMI) ≥ 18 and ≤ 36 kg/m2 and weigh at least 45kg at screening. Patients must be in good health as determined by medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory assessments at the time of screening, as judged by the Investigator. Key Exclusion Criteria: Part A / Single ascending doses: History or presence of any clinically relevant acute or chronic medical or psychiatric condition that could interfere with the subject's safety during the clinical study or expose the subject to undue risk as judged by the Investigator. After a minimum of 10 minutes supine rest at the time of screening or on Day -1: Systolic blood pressure <90 or >140 mmHg, or Diastolic blood pressure <50 or >90 mmHg, or Pulse <40 or >90 bpm Any clinically significant abnormalities in resting ECG at the time of screening or on Day -1 including prolonged QTcF (>450 ms for males; >470 ms for females using the mean of triplicate ECGs) and cardiac arrhythmias, as judged by the Investigator. Clinically significant abnormalities in renal function at screening. Clinically significant abnormalities in liver function at screening. Haemoglobin < 130 g/l for males or <120 g/l for females at screening. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP (Day 1). Malignancy within the past 5 years of screening with the exception of in situ removal of basal cell carcinoma or resected benign colonic polyps. Any planned major surgery within the duration of the study or in the 30 days following study completion. History of latent or active tuberculosis or a positive QuantiFERON® TB Gold test at screening. Females who are pregnant, breast feeding, lactating or plan to be pregnant during the study period or 120 days after. Female subjects with a positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) at screening or on Day -1. Positive serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or human immunodeficiency virus (HIV) 1 and/or 2 antibodies at screening. A Positive test for active COVID -19 prior to dosing on Day 1. History of any drug and/or alcohol abuse in the past 2 years prior to screening. Regular alcohol consumption of >14 units per week. Positive urine drugs of abuse test and/or alcohol breath test at screening or on admission to the unit on Day -1 that cannot be accounted for by concomitant medication in the opinion of the Investigator. Current or previous use of tobacco, nicotine products or e-cigarettes in the past 6 months. Smoking history of > 5 pack years. Positive urine cotinine test at screening or Day -1. Receiving any of the prohibited concomitant medications as specified in Section 5.5.3.1. Known history of intolerance or hypersensitivity to AX-202 or to any other component of the formulation. Known history of intolerance to placebo or excipients. Participation in another clinical study with an experimental drug within 3 months (non-biologic), 6 months (biologic) or 5 half-lives, whichever is longer, before the administration of IMP. Part B / Multiple ascending doses: History or presence of any clinically relevant acute or chronic medical or psychiatric condition other than psoriasis that could interfere with the patient's safety during the clinical study or expose the patient to undue risk as judged by the Investigator. A diagnosis of non-plaque psoriasis. Plaque psoriasis restricted to the scalp, palms, soles and face. Pustular, erythrodermic, inverse, and guttate psoriasis Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) Diagnosis of psoriatic arthritis, uveitis, inflammatory bowel disease, or other immune-mediated conditions that are commonly associated with psoriasis for which a patient requires current systemic (oral, subcutaneous [SC], or IV) (including corticosteroids, immunosuppressants, biologics) immunosuppressant medical treatment. Presence of other skin conditions that could interfere with psoriasis evaluation or assessments as judged by the Investigator. After a minimum of 10 minutes supine rest at the time of screening or on Day -1: Systolic blood pressure <90 or >140 mmHg, or Diastolic blood pressure <50 or >90 mmHg, or Pulse <40 or >90 bpm 9. Any clinically significant abnormalities in resting ECG at the time of screening or on Day -1 including prolonged QTcF (>450 ms for males; >470 ms for females using the mean of triplicate ECG's) and cardiac arrhythmias, as judged by the Investigator. Clinically significant abnormalities in renal function at screening. Clinically significant abnormalities in liver function at screening. Haemoglobin <130 g/l for males or <120 g/l for females at screening. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP (Day 1). Malignancy within the past 5 years of screening with the exception of in-situ removal of basal cell carcinoma or resected benign colonic polyps. Any planned major surgery within the duration of the study or in the 30 days following study completion. History of latent or active tuberculosis, or a positive QuantiFERON® TB Gold result at screening. Females who are pregnant, breast feeding, lactating or plan to be pregnant during the study period or 120 days after. Female patients with a positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) at screening or on Day -1. Positive serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or human immunodeficiency virus (HIV) 1 and/or 2 antibodies at screening. A Positive test for active COVID -19 prior to dosing on Day 1. History of any drug and/or alcohol abuse in the past 2 years prior to screening. Regular alcohol consumption of >14 units per week. Positive urine drugs of abuse test and/or alcohol breath test at screening or on admission to the unit on Day -1 that cannot be accounted for by concomitant medication in the opinion of the Investigator. Receiving any of the prohibited concomitant medications as specified in Section 5.5.3.2. Any clinically significant infection requiring antimicrobial treatment in the 2 weeks prior to Day 1. Known history of intolerance or hypersensitivity to AX-202 or to any other component of the formulation. Known history of intolerance to placebo or excipients. Participation in another clinical study with an experimental drug within 3 months (non-biologic), 6 months (biologic) or 5 half-lives, whichever is longer, before the administration of IMP.

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
Interventional Model Description: Single-ascending doses in healthy subjects and multiple ascending doses in patients with mild to moderate chronic plaque psoriasis
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AX-202<br>Single and multiple ascending doses of AX-202 | Biological: AX-202<br>* Humanized monoclonal antibody<br>|
| Placebo Comparator: Placebo<br>Single and multiple doses of placebo | Biological: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of a single ascending IV dose of AX-202 in healthy subjects and multiple ascending IV doses of AX-202 in patients with mild to moderate chronic plaque psoriasis by monitoring of adverse events. | Number of patients with AE's | Until 100 days after last dose | 
| To assess the safety and tolerability of a single ascending IV dose of AX-202 in healthy subjects and multiple ascending IV doses of AX-202 in patients with mild to moderate chronic plaque psoriasis by physical examinations. | Number of patients with clinically significant findings on physical examinations | Until 100 days after last dose | 
| To assess the safety and tolerability of a single ascending IV dose of AX-202 in healthy subjects and multiple ascending IV doses of AX-202 in patients with mild to moderate chronic plaque psoriasis by assessment of infusion related reactions | Number of patients with infusion related reactions | Until 100 days after last dose | 
| To assess the safety and tolerability of a single ascending IV dose of AX-202 in healthy subjects and multiple ascending IV doses of AX-202 in patients with mild to moderate chronic plaque psoriasis by monitoring of vital signs | Number of patients with clinically significant changes from baseline in vital signs | Until 100 days after last dose | 
| To assess the safety and tolerability of a single ascending IV dose of AX-202 in healthy subjects and multiple ascending IV doses of AX-202 in patients with mild to moderate chronic plaque psoriasis by monitoring of clinical laboratory parameters | Number of patients with clinically significant change from baseline in clinical laboratory test results. | Until 100 days after last dose | 
| To assess the safety and tolerability of a single ascending IV dose of AX-202 in healthy subjects and multiple ascending IV doses of AX-202 in patients with mild to moderate chronic plaque psoriasis by ECG monitoring | Number of patients with clinically significant change from baseline in ECG parameters | Until 100 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterise systemic PK of AX-202 after a single ascending IV dose in healthy subjects and after multiple ascending IV doses in patients with mild to moderate chronic plaque psoriasis. | Calculation of maximum serum concentration (Cmax) of AX-202 | Until 100 days after last dose | 
| To characterise systemic PK of AX-202 after a single ascending IV dose in healthy subjects and after multiple ascending IV doses in patients with mild to moderate chronic plaque psoriasis. | Calculation of time to maximum concentration (tmax) of AX-202 | Until 100 days after last dose | 
| To characterise systemic PK of AX-202 after a single ascending IV dose in healthy subjects and after multiple ascending IV doses in patients with mild to moderate chronic plaque psoriasis. | Calculation of the area under the plasma concentration-time curve (AUC) | Until 100 days after last dose | 
| To characterise systemic PK of AX-202 after a single ascending IV dose in healthy subjects and after multiple ascending IV doses in patients with mild to moderate chronic plaque psoriasis. | Calculation of the half-life of AX-202 | Until 100 days after last dose | 
| To characterise systemic PK of AX-202 after a single ascending IV dose in healthy subjects and after multiple ascending IV doses in patients with mild to moderate chronic plaque psoriasis. | Calculation of the clearance (CL) of AX-202 | Until 100 days after last dose | 
| To characterise systemic PK of AX-202 after a single ascending IV dose in healthy subjects and after multiple ascending IV doses in patients with mild to moderate chronic plaque psoriasis. | Calculation of volume of distribution at steady state (Vss) | Until 100 days after last dose | 
| To evaluate immunogenicity of AX-202 after a single ascending IV dose in healthy subjects and after multiple ascending IV doses in patients with mild to moderate chronic plaque psoriasis. | Number of participants with anti-drug antibodies against AX-202 | Until 100 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single Ascending Doses, Multiple Ascending Doses, AX-202