A Single and Multiple Inhaled Dose, 4-Part Study of KN-002 IP
Research type
Research Study
Full title
A Phase I Randomized, Double-Blinded, Placebo-Controlled, 4-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KN-002 by Inhalation of Single Ascending Doses in Healthy Subjects and Multiple Ascending Doses in Subjects with Stable Mild Asthma and a Repeated Dose in Subjects with Moderate to Severe Asthma and Subjects with Chronic Obstructive Pulmonary Disease.
IRAS ID
292966
Contact name
Frazer Morgan
Contact email
Sponsor organisation
Kinaset Therapeutics Incorporated
Eudract number
2020-005897-81
Duration of Study in the UK
0 years, 6 months, 6 days
Research summary
Research Summary
The sponsor, Kinaset Therapeutics Inc., is developing a new experiemental drug called KN-002 IP for the puspose of treating Asthma (a lung condition that causes breathing difficulties).Asthma is a lung disease associated with inflammation of the airways. This inflammation restricts the airflow to the lungs and can result in wheezing and shortness of breath. This can occur randomly or after being exposed to a trigger. Common triggers can include pollution, cold air, exercise and allergens (things a person may be allergic to). Asthma symptoms are usually reversible with the use of medications designed to reduce the inflammation and open the airways.
This study is divided into two parts:
Part 1 will assess the safety and tolerability of a single ascending dose of inhaled KN-002 IP in healthy participants. Blood and Urine samples will be taken to measure the levels of study medication in the body and the time it takes for the body to break it down (known as ‘Pharmacokinetic’ (PK) analysis).
Part 2 will assess the safety and tolerability of multiple ascending doses of inhaled KN-002 IP in participants with stable, mild asthma. Blood and urine samples will be taken for ‘Pharmacokinetic’ (PK) analysis and FeNO (a test to measure the level of inflammation within the lungs by breathing into an electronic device) measurements will be used to asses how the drug affects the body (known as 'Pharmacodynamic' (PD) analysis).The study will compare the effects of KN-002 IP to a placebo as a control, which allows us to evaluate the true effect of the experimental drug.
Summary of Results
In Part 1, a total of 49 healthy participants were enrolled across 6 groups, with each group consisting of approximately 8 participants (6 active: 2 placebo). Each subsequent group received a higher dose than the previous group (0.2 mg, 0.6 mg, 2.0 mg, 4.0 mg, 6.0 mg, and 12.0 mg). Of these 49 volunteers, 37 received a single dose of the study drug (KN-002) whereas the other 12 received placebo (dummy drug with no active ingredients).In Part 1, there were 11 instances of mild or moderate side effects being reported after KN-002 was administered (treatment-emergent adverse events [TEAEs]); these were all considered unrelated to study medication. There were no serious adverse events. A single dose of KN-002 was shown to be safe and well tolerated in healthy volunteers at all dose levels.
In Part 2, a total of 32 participants with stable, mild asthma, who had never used inhaled corticosteroid therapy, were enrolled across 4 groups. Each group comprised 8 subjects with 6 receiving active and two receiving placebo. Each subsequent group received a higher dose than the previous group (0.6 mg, 2.0 mg, 4.0 mg, and 8.0 mg). Of these 32 participants, 24 received KN-002 whereas 8 received placebo. Participants received daily doses of KN-002 or placebo once-daily (groups 1 and 2) or twice-daily (groups 3 and 4) over 9 days, followed by a single morning dose on Day 10.
In total 33 mild or moderate TEAEs were reported; these were all considered unrelated to the study medication. There were no serious adverse events. Multiple doses of KN-002 were shown to be safe and well tolerated in patients with stable, mild asthma at all dose levels.
In Part 3, a total of 23 participants with moderate-severe asthma, who had been using inhaled corticosteroid therapy combined with a long-acting bronchodilator for at least 3 months, were enrolled into a single group. Seventeen participants received 4.0 mg of KN-002 and 6 participants received placebo twice-daily over 9 days, followed by a single morning dose on Day 10.
During Part 3 mild or moderate TEAEs were reported by 12 participants. Two TEAEs (moderate headache and mild sore throat) were considered possibly related to the study medication however, both events resolved during the treatment period with no change in dosing. There were no serious adverse events. The administration of a 4.0 mg dose of KN-002 twice-daily was shown to be safe and well tolerated in patients with moderate-severe asthma.
In Part 4, a total of 13 participants with Chronic Obstructive Pulmonary Disease (COPD), who had been using inhaled corticosteroid therapy alone or in combination with a long-acting beta agonist or muscarinic antagonist, were enrolled into a single group. Nine participants received 4.0 mg of KN-002 and 4 participants received placebo twice-daily over 9 days, followed by a single morning dose on Day 10.
In total 11 TEAEs were reported by 7 participants. Two TEAEs (fatigue and breathing difficulty) were reported as severe and potentially drug-related in a medically complex participant, but were subsequently described as related to study procedures, not study treatment. There were no serious adverse events. The administration of a 4.0 mg dose of KN-002 twice daily was shown to be safe and well tolerated in COPD patients.Overall single and multiple doses of inhaled KN-002 were well tolerated and no safety findings of concern were observed in healthy subjects or those with mild asthma, moderate to severe asthma or COPD.
Pharmacokinetic (PK) data (data measuring the levels of study medication in the body and the time taken for the body to break the medication down) indicated that repeated administration of KN-002 over a 10-day period in participants with mild asthma, moderate-severe asthma, and COPD resulted in levels of KN-002 in the body that were proportional to the dose of KN-002 received, with low urinary excretion of study medication in all groups.
Exhaled nitrous oxide ‘FeNO’ testing was used throughout the study to measure the level of inflammation present within the lungs. To be eligible for participation in the study participants in Parts 2 and 3 were required to have concentrations of FeNO that were higher than normal levels.
Analysis of the data showed that treatment with doses of 2 mg once-daily and above reduced FeNO levels in subjects with mild and moderate to severe asthma. A 0.6 mg once-daily dose did not improve FeNO levels when administered twice-daily to over a 10-day period to subjects with mild asthma. Therefore a 0.6 mg once daily dose is not considered to be a pharmacologically active.
In Part 4, participants were not required to have FeNO above normal levels. The 10-day administration of a 4 mg twice-daily dose to subjects with COPD resulted in an improvement in FeNO levels.
Overall results showed the twice-daily administration of KN-002 doses of 2 mg once-daily and above improved FeNO levels, a measure of airway inflammation, in participants with asthma or COPD.
REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
21/NW/0004
Date of REC Opinion
12 Feb 2021
REC opinion
Favourable Opinion