A Study to Assess the Efficacy, Safety, and Tolerability of CAT-354 in Subjects With Asthma

Change in doubling concentrations of methacholine was calculated as Log2 PC20 (Visit x) - Log2 PC20 (Baseline), where x was the post-baseline assessment (Day 28) and PC20 was provocative concentration of methacholine causing 20 percent fall in forced expiratory volume in 1 second (FEV1). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Change in doubling concentration was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.

The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.

The FVC was volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.

Percentage of FEV1 was calculated as (FEV1/FVC)*100. It signified the percentage of the total amount of air exhaled from the lungs during the first second of forced exhalation. FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Result was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.

The ACQ is questionnaire that comprises of 7-questions evaluating participant's asthma control. Six self-administered questions assess asthma control over the past week covering nocturnal waking, morning symptoms, activity limitations, shortness of breath, wheezing, and short-acting bronchodilator use; using 7-point ordinal rating scale from 0 (good control) to 6 (poor control). Seventh question is completed by a health professional on forced expiratory volume in 1 second (FEV1) percentage (%) predicted; scale: 0 (greater than [>] 95% predicted) to 6 (less than [<] 50% predicted. Final score is the average score of the 7 questions, with a score range of 0 (well controlled) to 6 (extremely poor controlled). Result was summarized for sub-therapeutic dose (placebo and CAT-354 1 mg/kg) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.

The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.

Participants recorded asthma symptoms, use of reliever inhalers (beta-agonist use for symptom relief and as prophylaxis), and morning and evening peak expiratory flow (PEF) measurements in a diary.

Exacerbation was defined as: Mild (determined from diary data) - 2 consecutive days satisfying the same or 1 of the following criteria: any night with awakening(s) due to asthma or morning PEF 20 % or more below baseline where baseline = average of the 10 days before randomization or as-needed medication use of 2 inhalations or more in 24 hours above baseline where baseline = average of the 10 days before randomization. Severe (determined by taking an exacerbation update and history): deterioration of asthma resulting in emergency treatment or hospitalization or need for oral steroids for 3 days or more (as judged by the Investigator).

Peak flow is a participant's maximum speed of expiration.

The AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants are asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean response to all questions. The 4 domain scores are the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment).

Accumulation ratio (RA) is calculated for Cmax, Cmin and AUC as RA for Cmax = Cmax (56 - 84)/Cmax (0 - 28); Similarily, RA for Cmin = Cmin (56 - 84)/Cmin (0 - 28) and RA for AUC= AUC (56 - 84)/AUC (0 - 28) where Cmax (0 - 28) and Cmax (56 - 84) are the maximum observed serum concentration after first dose (Day 0 to Day 28) and after third dose (Day 56 to Day 84), respectively; Cmin (0 - 28) and Cmin (56 - 84) are the minimum observed serum concentration after first and third dose, respectively; AUC (0 - 28) and AUC (56 - 84) are the area under the serum concentration time curve over a dosage interval determined after first and third dose, respectively.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 84 that were absent before treatment or that worsened relative to pre-treatment state.