A Phase 1, First in Human Study to Investigate the Safety and Tolerability of PA401

Study Overview
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Brief Summary
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The purpose of this study is to examine the safety, tolerability, immunogenicity and the way the body absorbs, distributes, breaks down and excretes various increasing single and multiple subcutaneous doses of PA401 in healthy subjects. This study will also look at the effect of PA401 on inflammation in the lungs following an inhaled lipopolysaccharide (LPS) challenge (LPS is a bacterial cell wall fragment) and sputum induction (a procedure performed to help to cough up sputum (phlegm)) after a single subcutaneous dose of two dose levels.

Official Title
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A Phase 1, FIH, Double-blind, Randomised Placebo-controlled Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of PA401, and the Effects of PA401 Following LPS Challenge, in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: PA401
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult males aged 18 to 65 years Exclusion Criteria: Subjects with a clinically relevant medical history

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: PA401<br>PA401 is a potent inhibitor of neutrophil activation and transmigration under development as a novel parenteral anti-inflammatory therapy for respiratory indications such as chronic obstructive pulmonary disease (COPD) and Cystic Fibrosis (CF). PA401 is a genetically engineered and recombinantly expressed mutant of the bioactive form of human interleukin-8. | Biological: PA401<br>* Part A of Study: Subcutaneous, 0.1mg to 50mg, single ascending doses Part B of Study: Subcutaneous, up to 17.1mg, single dose<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse Events |  | up to 14 days post dose | 
| Immunogenicity | Anti-drug antibody data | Up to 28 days post dose | 
| Assessment of the Effect of PA401 on Induced Sputum Total Neutrophils | Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils | 5.5 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) |  | Up to 12 time-points up to 48 hours post dose | 
| Pharmacokinetic Parameters: Time of Occurrence of the Maximum Observed Plasma Concentration (Tmax) |  | Up to 12 time-points up to 48 hours post dose | 
| Pharmacokinetic Parameters: Terminal Half-life (t1/2) |  | Up to 12 time-points up to 48 hours post dose | 
| Pharmacokinetic Parameters: Area Under the Plasma Concentration-time Curve From Zero to Infinity |  | Up to 12 time-points up to 48 hours post dose | 
| Assessment of the Effect of PA401 on Induced Sputum Percentage Neutrophils | Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils | 5.5 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, First in Human, Healthy Volunteers, Lipopolysaccharide Challenge