Single and Multiple Ascending Dose Study of KN-002

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blinded, placebo controlled study. The study consists of 4 parts: Part 1 is a single ascending dose (SAD) study in healthy volunteers; Part 2 is a multiple ascending dose (MAD) study in subjects with stable, mild asthma; Part 3 is a repeat dose in patients with moderate to severe asthma and Part 4 is a repeat dose in patients with COPD.

Official Title
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Phase 1 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, PK, and PD of Single Ascending Doses of KN-002 in Healthy Subjects and Multiple Ascending Doses of KN-002 in Subjects With Mild Asthma, Moderate-Severe Asthma and COPD

Conditions
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Asthma COPD

Intervention / Treatment
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* Drug: KN-002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 - 55 years old Willing and able to give informed consent and comply with the study Body mass index (BMI) 18 to 32 kg/m2 and weighs at least 50 kg Women of child bearing potential must have a negative pregnancy test and use a highly efficient birth control method Pre-bronchodilator FEV1 ≥ 70 and ≥80% for Part 1 and Part 2 participants, respectively Pre-Bronchodilator FEV1 ≥50% predicted and ≤100% for Part 3 Post Bronchodilator FEV1 ≥40 and ≤ 85% for Part 4 Exclusion Criteria: Clinically significant laboratory test abnormalities Clinically significant abnormal blood pressure and/or pulse rate Resting ECG clinically significant abnormalities Respiratory tract infection within 6 weeks of screening Positive test for active COVID-19 within 2 days prior to administration of IMP

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KN-002 for SAD (Part 1)<br>Up to 6 cohorts with 6 of 8 subjects per cohort randomised to receive KN-002 | Drug: KN-002<br>* KN-002 dry powder inhaler<br>|
| Placebo Comparator: Placebo for SAD (Part 1)<br>Up to 6 cohorts with 2 of 8 subjects per cohort randomised to receive placebo | Drug: KN-002<br>* KN-002 dry powder inhaler<br>|
| Experimental: KN-002 for MAD (Part 2)<br>Up to 4 cohorts with 6 of 8 subjects per cohort randomised to receive KN-002 | Drug: KN-002<br>* KN-002 dry powder inhaler<br>|
| Experimental: Placebo for MAD (Part 2)<br>Up to 4 cohorts with 2 of 8 subjects per cohort randomised to receive placebo | Drug: KN-002<br>* KN-002 dry powder inhaler<br>|
| Experimental: KN-002 for Part 3<br>Single cohort with up to 18 of 24 subjects randomised to active treatment | Drug: KN-002<br>* KN-002 dry powder inhaler<br>|
| Experimental: Placebo for Part 3<br>Single cohort with up to 6 of 24 subjects randomised to placebo treatment | Drug: KN-002<br>* KN-002 dry powder inhaler<br>|
| Experimental: KN-002 for Part 4<br>Single cohort with up to 18 of 24 subjects randomised to active treatment | Drug: KN-002<br>* KN-002 dry powder inhaler<br>|
| Experimental: Placebo for Part 4<br>Single cohort with up to 6 of 24 subjects randomised to placebo treatment | Drug: KN-002<br>* KN-002 dry powder inhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability (Parts 1, 2, 3 and 4) via an assessment of the incidence of treatment-related adverse events | To assess the safety and tolerability of KN-002 via the assessment of the number, severity and type of treatment emergent adverse events post single and repeat dose administration to healthy volunteers and patients with mild asthma, moderate to severe asthma and COPD | Day 1 to 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (Parts 1, 2, 3 and 4) via the determination of area under the curve (AUC) | KN-002 pharmacokinetics after single and repeat dosing to healthy volunteers and patients with mild asthma, moderate to severe asthma and COPD: | Day 1 to 17 | 
| Pharmacokinetics (Parts 1, 2, 3 and 4) via the determination of maximum plasma concentrations (Cmax) | KN-002 pharmacokinetics after single and repeat dosing to healthy volunteers and patients with mild asthma, moderate to severe asthma and COPD: | Day 1 to 17 | 
| Pharmacodynamics (Parts 2, 3 and 4) via changes in fractional exhaled nitric oxide (FeNO) levels | Change of fractional exhaled nitric oxide (FeNO) levels after repeated dosing to patients with mild asthma, moderate to severe asthma and COPD | Day 1 to 17 |