Asthma
Conditions
Keywords
Asthma, CAT-354, Tralokinumab
Brief summary
To investigate the effects of CAT-354 on airway hyper-responsiveness (AHR) in uncontrolled asthma.
Detailed description
This is a randomized, stratified, double-blind, placebo-controlled, multicenter, multinational study in subjects with uncontrolled asthma despite optimal treatment. Following confirmation of eligibility, subjects will be randomly assigned on Day 0, to 1 of 4 dose groups 1 mg/kg CAT-354, 5 mg/kg CAT-354, 10 mg/kg CAT or Placebo to match all doses of CAT-354. Doses of the assigned treatment will be administered on three occasions 28 days apart. Subjects will be assessed for efficacy, including airway hyper-responsiveness (AHR), safety, pharmacokinetic, pharmacodynamics and immunogenicity until Day 84 post-first dose.
Interventions
OTHERPlacebo
Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56.
BIOLOGICALCAT-354 1 mg/kg
CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
BIOLOGICALCAT-354 5 mg/kg
CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
OTHERCAT-354 10 mg/kg
CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56.
Sponsors
Cambridge Antibody Technology
PRA Health Sciences
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent is obtained prior to any study related procedure taking place * Women either infertile (example \[e.g.\], hysterectomized, sterile or post-menopausal with amenorrhea of least 1 year duration) or who are practicing an acceptable form of birth control * Uncontrolled (refractory) asthma despite treatment with a minimum dose of 800 microgram (mcg) beclomethasonedipropionate or equivalent inhaled corticosteroid per day plus 1 or more additional controller, that is, long-acting beta-agonist, leukotriene antagonist or theophylline. Oral corticosteroids (not parenteral) as additional treatment at any dose are acceptable * A forced expiratory volume in 1 second (FEV1) acceptable for airway hyper-responsiveness (AHR) challenge tests (greater than 60 percent of predicted normal) on the challenge days * A provocative concentration of methacholine causing a 20 percent fall in FEV1 (PC20) less than 4 milligram per milliliter (mg/mL) * Aged 18-80 years * A 12-lead electrocardiogram (ECG) with no-clinically significant abnormalities * Clinical chemistry, hematology and urinalysis results within the laboratory reference ranges or deemed not clinically significant by the Investigator * Body weight of less than 130 kilogram (kg) * No other clinically significant abnormality on history and clinical examination * Able to comply with the requirements of the protocol.
Exclusion criteria
* Experienced a severe exacerbation within 28 days preceding Day -28/-14 to Day 0 * Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Day -28/-14 to Day 0 * Subjects with a history of allergic rhinitis, seasonal allergy or esophagitis must be optimally controlled and remain on a stable treatment regimen during the study * Participation in another study within 5 half-lives or 3 months of the start of this study, whichever is the longer * Lower respiratory tract infection within 6 weeks of Day -28/-14 to Day 0 * Current smokers or ex-smokers with greater than 10 pack-years * Blood donation (more than 550 mL) in the previous 2 months * Excessive intake of alcohol (as judged by the Investigator) or evidence of drug or solvent abuse * Subjects with a physician-diagnosis of any other significant lung disease, including a primary diagnosis of chronic obstructive pulmonary disease or bronchiectasis, or lung cancer, sarcoidosis, tuberculosis, pulmonary fibrosis and cystic fibrosis * Concurrent medication from Day -28/-14 to Day 0 (Screening visit) and for the duration of the study with any of the prohibited medications * Significant, uncontrolled disease including serious psychological disorders, chronic renal failure, uncontrolled hypertension * systolic blood pressure greater than 200 millimeters of mercury (mmHg), or diastolic blood pressure greater than 100 mmHg, heart disease, psoriasis requiring treatment and subjects who have had a heart attack or stroke within the 3 months preceding Day -28/-14 to Day 0, or who have a known aneurysm * Onset of uncontrolled seasonal allergy symptoms within 28 days preceding Day -28/-14 to Day 0 * Subjects with a history of allergic rhinitis, seasonal allergy or esophagitis must be optimally controlled and remain on a stable treatment regimen during the study * Any factor which, in the opinion of the Investigator, would jeopardize the evaluation or safety or be associated with poor adherence to the protocol (that is, inability to complete study diary, perform peak expiratory flow (PEF) measurements) * The subject's primary care physician recommends the subject should not take part in the study * Known hypersensitivity to CAT-354 or its components, to the challenge agents used in the study or to related drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Doubling Concentration of Methacholine at Day 28 | Baseline and Day 28 | 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 milligram/kilogram \[mg/kg\]) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Day 0 to 84 | The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. |
| Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination | Baseline, Day 56, 84 or early termination (any time before Day 84) | 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. |
| Forced Expiratory Volume in 1 Second (FEV1) | Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84) | 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. |
| Forced Vital Capacity (FVC) | Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84) | 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. |
| Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, Day 63, 84 or early termination (any time before Day 84) | 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. |
| Asthma Control Questionnaire (ACQ) Total Score | Baseline, Day 28, 56, 84 or early termination (any time before Day 84) | 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. |
| Number of Participants With Diary Data | Day 0, 4, 14, 28, 35, 56, 63 to Day and 84 | 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. |
| Morning Peak Flow and Peak Flow Variability | Day 0 to Day 84 | Peak flow is a participant's maximum speed of expiration. |
| Adult Asthma Quality of Life (QoL) Questionnaire Final Score | Day 0, 28, 84 or early termination (any time before Day 84) | 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). |
| Maximum Observed Serum Concentration (Cmax) for CAT-354 | Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56 | — |
| Minimum Observed Serum Concentration (Cmin) for CAT-354 | Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56 | — |
| Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56 | — |
| Accumulation Ratio for CAT-354 (RA) | Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56 | 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. |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 0 to 84 | 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. |
| Number of Participants With Exacerbations | Day 0 to Day 84 | 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). |
Countries
Australia, Germany, Netherlands, Poland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to CAT-354 intravenous infusion over 60 minutes on Day 0, 28 and 56. | 3 |
| CAT-354 1 mg/kg CAT-354 1 milligram/kilogram (mg/kg) of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56. | 3 |
| CAT-354 5 mg/kg CAT-354 5 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56. | 4 |
| CAT-354 10 mg/kg CAT-354 10 mg/kg of body weight intravenous infusion over 60 minutes on Day 0, 28 and 56. | 4 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Study termination | 2 | 1 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | CAT-354 1 mg/kg | CAT-354 5 mg/kg | CAT-354 10 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 34.00 years STANDARD_DEVIATION 11.136 | 34.00 years STANDARD_DEVIATION 14.933 | 37.75 years STANDARD_DEVIATION 9.878 | 40.75 years STANDARD_DEVIATION 15.086 | 37.00 years STANDARD_DEVIATION 11.708 |
| Gender Female | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants |
| Gender Male | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 2 / 2 | 4 / 4 | 2 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 | 0 / 4 | 1 / 4 |
Outcome results
Primary
Change From Baseline in Doubling Concentration of Methacholine at Day 28
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 milligram/kilogram \[mg/kg\]) and therapeutic dose (CAT-354 5 mg/kg and CAT-354 10 mg/kg), as per planned analysis.
Time frame: Baseline and Day 28
Population: Safety population included all participants who received at least 1 dose of study medication. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 28 | Change at Day 28 (n=5, 4) | -0.207 log2 milligram/deciliter (mg/dL) | Standard Deviation 1.045 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 28 | Baseline (n=8, 5) | -0.604 log2 milligram/deciliter (mg/dL) | Standard Deviation 2.408 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 28 | Baseline (n=8, 5) | -1.545 log2 milligram/deciliter (mg/dL) | Standard Deviation 0.8952 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 28 | Change at Day 28 (n=5, 4) | 0.125 log2 milligram/deciliter (mg/dL) | Standard Deviation 2.3433 |
Secondary
Accumulation Ratio for CAT-354 (RA)
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.
Time frame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Population: PK population included all participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Accumulation Ratio for CAT-354 (RA) | RA for Cmax | 2.00 ratio |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Accumulation Ratio for CAT-354 (RA) | RA for Cmin | 1.20 ratio |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Accumulation Ratio for CAT-354 (RA) | RA for AUC | 1.49 ratio |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Accumulation Ratio for CAT-354 (RA) | RA for Cmax | 1.65 ratio |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Accumulation Ratio for CAT-354 (RA) | RA for AUC | 1.31 ratio |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Accumulation Ratio for CAT-354 (RA) | RA for Cmin | 1.54 ratio |
| CAT-354 10 mg/kg | Accumulation Ratio for CAT-354 (RA) | RA for Cmin | 1.73 ratio |
| CAT-354 10 mg/kg | Accumulation Ratio for CAT-354 (RA) | RA for AUC | 1.64 ratio |
| CAT-354 10 mg/kg | Accumulation Ratio for CAT-354 (RA) | RA for Cmax | 1.30 ratio |
Secondary
Adult Asthma Quality of Life (QoL) Questionnaire Final Score
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).
Time frame: Day 0, 28, 84 or early termination (any time before Day 84)
Population: Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.
Secondary
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354
Time frame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Population: PK population included all participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After second dose (Day 28) | 408 microgram*day/milliliter (mcg*day/mL) |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After first dose (Day 0) | 335 microgram*day/milliliter (mcg*day/mL) |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After third dose (Day 56) | 499 microgram*day/milliliter (mcg*day/mL) |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After second dose (Day 28) | 4720 microgram*day/milliliter (mcg*day/mL) |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After first dose (Day 0) | 2820 microgram*day/milliliter (mcg*day/mL) |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After third dose (Day 56) | 3690 microgram*day/milliliter (mcg*day/mL) |
| CAT-354 10 mg/kg | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After first dose (Day 0) | 2090 microgram*day/milliliter (mcg*day/mL) |
| CAT-354 10 mg/kg | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After third dose (Day 56) | 3420 microgram*day/milliliter (mcg*day/mL) |
| CAT-354 10 mg/kg | Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0 - t]) for CAT-354 | After second dose (Day 28) | 3080 microgram*day/milliliter (mcg*day/mL) |
Secondary
Asthma Control Questionnaire (ACQ) Total Score
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.
Time frame: Baseline, Day 28, 56, 84 or early termination (any time before Day 84)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Day 56 (n=2, 2) | 1.43 units on a scale | Standard Deviation 0.808 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Baseline (n=8, 5) | 2.44 units on a scale | Standard Deviation 0.737 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Day 84 (n=2, 2) | 1.57 units on a scale | Standard Deviation 1.01 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Day 28 (n=5, 4) | 2.00 units on a scale | Standard Deviation 0.416 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Early Termination (n=5, 3) | 1.72 units on a scale | Standard Deviation 1.304 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Early Termination (n=5, 3) | 0.57 units on a scale | Standard Deviation 0.378 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Day 28 (n=5, 4) | 1.46 units on a scale | Standard Deviation 0.914 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Day 56 (n=2, 2) | 1.50 units on a scale | Standard Deviation 1.111 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Day 84 (n=2, 2) | 2.36 units on a scale | Standard Deviation 0.101 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Asthma Control Questionnaire (ACQ) Total Score | Baseline (n=8, 5) | 1.77 units on a scale | Standard Deviation 0.861 |
Secondary
Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination
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.
Time frame: Baseline, Day 56, 84 or early termination (any time before Day 84)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure, and 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination | Change at Day 84 (n=2, 2) | -0.038 log2 mg/dL | Standard Deviation 0.141 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination | Change at Day 56 (n=2, 2) | 0.062 log2 mg/dL | Standard Deviation 1.1309 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination | Change at Early termination (n=3, 2) | -0.514 log2 mg/dL | Standard Deviation 0.8636 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination | Change at Day 84 (n=2, 2) | -1.846 log2 mg/dL | Standard Deviation 0.0431 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination | Change at Day 56 (n=2, 2) | -1.423 log2 mg/dL | Standard Deviation 0.4059 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Change From Baseline in Doubling Concentration of Methacholine at Day 56, 84 or Early Termination | Change at Early termination (n=3, 2) | 0.417 log2 mg/dL | Standard Deviation 0.984 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1)
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.
Time frame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84)
Population: Safety population included all participants who received at least 1 dose of study medication. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 0: Predose (n=8, 5) | 2.718 liters | Standard Deviation 0.5458 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 0: 30 minutes postdose (n=8, 5) | 2.684 liters | Standard Deviation 0.5695 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 0: 6 hours postdose (n=8, 5) | 2.606 liters | Standard Deviation 0.5731 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 28: 30 minutes postdose (n=4, 4) | 2.535 liters | Standard Deviation 0.5639 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 56: Predose (n=2, 2) | 2.555 liters | Standard Deviation 0.6718 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 56: 6 hours postdose (n=2, 2) | 2.510 liters | Standard Deviation 0.7071 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 84: (n=2, 2) | 2.680 liters | Standard Deviation 0.7778 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 4 (n=8, 5) | 2.814 liters | Standard Deviation 0.6048 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 14 (n=6, 5) | 2.323 liters | Standard Deviation 0.5703 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 28: Predose (n=5, 4) | 2.598 liters | Standard Deviation 0.4676 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 28: 6 hours postdose (n=4, 4) | 2.400 liters | Standard Deviation 0.5254 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 35 (n= 4, 4) | 2.260 liters | Standard Deviation 0.5464 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 56: 30 minutes postdose (n=2, 2) | 2.705 liters | Standard Deviation 0.799 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 63 (n= 2, 2) | 2.505 liters | Standard Deviation 0.6859 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Early Termination (n=4, 3) | 3.018 liters | Standard Deviation 0.5803 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 0: 6 hours postdose (n=8, 5) | 2.550 liters | Standard Deviation 0.4304 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 35 (n= 4, 4) | 2.778 liters | Standard Deviation 0.4228 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 0: 30 minutes postdose (n=8, 5) | 2.624 liters | Standard Deviation 0.4126 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 4 (n=8, 5) | 2.606 liters | Standard Deviation 0.2919 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 28: 6 hours postdose (n=4, 4) | 2.665 liters | Standard Deviation 0.2748 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 28: 30 minutes postdose (n=4, 4) | 2.918 liters | Standard Deviation 0.2822 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 14 (n=6, 5) | 2.520 liters | Standard Deviation 0.0812 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 56: Predose (n=2, 2) | 2.700 liters | Standard Deviation 0.3677 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 56: 30 minutes postdose (n=2, 2) | 2.830 liters | Standard Deviation 0.1697 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 63 (n= 2, 2) | 2.580 liters | Standard Deviation 0.0283 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 56: 6 hours postdose (n=2, 2) | 2.690 liters | Standard Deviation 0.2404 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 28: Predose (n=5, 4) | 2.850 liters | Standard Deviation 0.2082 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 84: (n=2, 2) | 2.540 liters | Standard Deviation 0.4101 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Early Termination (n=4, 3) | 2.867 liters | Standard Deviation 0.44 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) | Day 0: Predose (n=8, 5) | 2.640 liters | Standard Deviation 0.3994 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC)
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.
Time frame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, Day 63, 84 or early termination (any time before Day 84)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 35 (n=4, 4) | 62.500 percentage of FVC | Standard Deviation 7.5498 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 56: Predose (n=2, 2) | 68.000 percentage of FVC | Standard Deviation 8.4853 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 56: 30 minutes postdose (n=2, 2) | 71.000 percentage of FVC | Standard Deviation 11.3137 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 63 (n=2, 2) | 66.500 percentage of FVC | Standard Deviation 9.1924 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 56: 6 hours postdose (n=2, 2) | 67.000 percentage of FVC | Standard Deviation 7.0711 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 84 (n=2, 2) | 71.500 percentage of FVC | Standard Deviation 9.1924 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 14 (n=6, 5) | 66.667 percentage of FVC | Standard Deviation 7.5011 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 28: 30 minutes postdose (n=4, 4) | 66.500 percentage of FVC | Standard Deviation 13.9881 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Early Termination (n=4, 3) | 77.750 percentage of FVC | Standard Deviation 9.8107 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 28: Predose (n=5, 4) | 67.400 percentage of FVC | Standard Deviation 13.1263 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 0: Predose (n=8, 5) | 71.875 percentage of FVC | Standard Deviation 10.3156 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 28: 6 hours postdose (n=4, 4) | 63.750 percentage of FVC | Standard Deviation 12.339 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 0: 30 minutes postdose (n=8, 5) | 70.250 percentage of FVC | Standard Deviation 9.1613 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 4 (n=8, 5) | 71.000 percentage of FVC | Standard Deviation 13.1909 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 0: 6 hours postdose (n=8, 5) | 69.125 percentage of FVC | Standard Deviation 12.5178 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 4 (n=8, 5) | 69.400 percentage of FVC | Standard Deviation 8.7063 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 0: 6 hours postdose (n=8, 5) | 69.600 percentage of FVC | Standard Deviation 12.1984 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 28: Predose (n=5, 4) | 74.500 percentage of FVC | Standard Deviation 11.2694 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 14 (n=6, 5) | 68.800 percentage of FVC | Standard Deviation 8.167 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 28: 30 minutes postdose (n=4, 4) | 74.500 percentage of FVC | Standard Deviation 9.6782 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 28: 6 hours postdose (n=4, 4) | 71.250 percentage of FVC | Standard Deviation 13.8173 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 35 (n=4, 4) | 71.750 percentage of FVC | Standard Deviation 7.8049 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 56: Predose (n=2, 2) | 80.000 percentage of FVC | Standard Deviation 19.799 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 56: 30 minutes postdose (n=2, 2) | 81.000 percentage of FVC | Standard Deviation 15.5563 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 56: 6 hours postdose (n=2, 2) | 76.500 percentage of FVC | Standard Deviation 14.8492 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 63 (n=2, 2) | 72.500 percentage of FVC | Standard Deviation 9.1924 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 84 (n=2, 2) | 75.500 percentage of FVC | Standard Deviation 19.0919 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Early Termination (n=4, 3) | 69.000 percentage of FVC | Standard Deviation 5.5678 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 0: Predose (n=8, 5) | 72.600 percentage of FVC | Standard Deviation 11.4149 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Expiratory Volume in 1 Second (FEV1) as Percentage of Forced Vital Capacity (FVC) | Day 0: 30 minutes postdose (n=8, 5) | 71.600 percentage of FVC | Standard Deviation 13.1833 |
Secondary
Forced Vital Capacity (FVC)
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.
Time frame: Predose, 30 minutes and 6 hours post-end of infusion on Day 0, 28 and 56; Day 4, 14, 35, 63, 84 or early termination (any time before Day 84)
Population: Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 28: 6 hours postdose (n=4, 4) | 3.810 liters | Standard Deviation 0.7409 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 0: 30 minutes postdose (n= 8, 5) | 3.823 liters | Standard Deviation 0.65 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 28: Predose (n=5, 4) | 3.908 liters | Standard Deviation 0.767 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 0: 6 hours postdose (n= 8, 5) | 3.808 liters | Standard Deviation 0.7718 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 35 (n=4, 4) | 3.613 liters | Standard Deviation 0.6874 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 4 (n= 8, 5) | 3.988 liters | Standard Deviation 0.6058 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 14 (n=6, 5) | 3.462 liters | Standard Deviation 0.5926 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 56: Predose (n=2, 2) | 3.700 liters | Standard Deviation 0.5233 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 56: 30 minutes postdose (n=2, 2) | 3.775 liters | Standard Deviation 0.5303 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 56: 6 hours postdose (n=2, 2) | 3.715 liters | Standard Deviation 0.6435 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 28: 30 minutes postdose (n=4, 4) | 3.878 liters | Standard Deviation 0.7876 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 63 (n=2, 2) | 3.705 liters | Standard Deviation 0.5162 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 84: (n=2, 2) | 3.710 liters | Standard Deviation 0.6505 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Early Termination (n=4, 3) | 3.908 liters | Standard Deviation 0.807 |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Forced Vital Capacity (FVC) | Day 0: Predose (n= 8, 5) | 3.828 liters | Standard Deviation 0.8215 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Early Termination (n=4, 3) | 4.193 liters | Standard Deviation 0.8364 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 0: Predose (n= 8, 5) | 3.666 liters | Standard Deviation 0.6068 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 14 (n=6, 5) | 3.710 liters | Standard Deviation 0.522 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 28: Predose (n=5, 4) | 3.883 liters | Standard Deviation 0.6412 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 28: 6 hours postdose (n=4, 4) | 3.790 liters | Standard Deviation 0.483 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 35 (n=4, 4) | 3.920 liters | Standard Deviation 0.7777 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 56: 30 minutes postdose (n=2, 2) | 3.540 liters | Standard Deviation 0.4667 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 84: (n=2, 2) | 3.415 liters | Standard Deviation 0.3323 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 0: 30 minutes postdose (n= 8, 5) | 3.722 liters | Standard Deviation 0.6752 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 0: 6 hours postdose (n= 8, 5) | 3.722 liters | Standard Deviation 0.7297 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 4 (n= 8, 5) | 3.824 liters | Standard Deviation 0.7415 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 28: 30 minutes postdose (n=4, 4) | 3.980 liters | Standard Deviation 0.7951 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 56: Predose (n=2, 2) | 3.410 liters | Standard Deviation 0.3818 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 56: 6 hours postdose (n=2, 2) | 3.545 liters | Standard Deviation 0.3748 |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Forced Vital Capacity (FVC) | Day 63 (n=2, 2) | 3.575 liters | Standard Deviation 0.502 |
Secondary
Maximum Observed Serum Concentration (Cmax) for CAT-354
Time frame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Population: Pharmacokinetic (PK) population included all participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After third dose (Day 56) | 33.4 microgram/milliliter (mcg/mL) |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After first dose (Day 0) | 27.7 microgram/milliliter (mcg/mL) |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After second dose (Day 28) | 34.5 microgram/milliliter (mcg/mL) |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After third dose (Day 56) | 338 microgram/milliliter (mcg/mL) |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After first dose (Day 0) | 219 microgram/milliliter (mcg/mL) |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After second dose (Day 28) | 255 microgram/milliliter (mcg/mL) |
| CAT-354 10 mg/kg | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After third dose (Day 56) | 251 microgram/milliliter (mcg/mL) |
| CAT-354 10 mg/kg | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After second dose (Day 28) | 235 microgram/milliliter (mcg/mL) |
| CAT-354 10 mg/kg | Maximum Observed Serum Concentration (Cmax) for CAT-354 | After first dose (Day 0) | 163 microgram/milliliter (mcg/mL) |
Secondary
Minimum Observed Serum Concentration (Cmin) for CAT-354
Time frame: Predose, 10 minutes and 6 hours post-end of infusion on Day 0, 28 and 56
Population: PK population included all participants who received at least 1 dose of study medication and had sufficient post-dose blood samples to estimate Cmax. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After third dose (Day 56) | 9.70 mcg/mL |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After second dose (Day 28) | 7.91 mcg/mL |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After first dose (Day 0) | 4.84 mcg/mL |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After third dose (Day 56) | 85.5 mcg/mL |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After first dose (Day 0) | 51.8 mcg/mL |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After second dose (Day 28) | 54.1 mcg/mL |
| CAT-354 10 mg/kg | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After third dose (Day 56) | 68.4 mcg/mL |
| CAT-354 10 mg/kg | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After second dose (Day 28) | 64.4 mcg/mL |
| CAT-354 10 mg/kg | Minimum Observed Serum Concentration (Cmin) for CAT-354 | After first dose (Day 0) | 52.8 mcg/mL |
Secondary
Morning Peak Flow and Peak Flow Variability
Peak flow is a participant's maximum speed of expiration.
Time frame: Day 0 to Day 84
Population: Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.
Secondary
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
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.
Time frame: Day 0 to 84
Population: Safety population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
| Therapeutic-dose (CAT-354 5mg/kg and CAT-354 10mg/kg) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 2 participants |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
| Sub-therapeutic Dose (Placebo or CAT-354 1mg/kg) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 2 participants |
| CAT-354 10 mg/kg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 participants |
| CAT-354 10 mg/kg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 participants |
| CAT-354 10 mg/kg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 participants |
| CAT-354 10 mg/kg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 1 participants |
Secondary
Number of Participants With Diary Data
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.
Time frame: Day 0, 4, 14, 28, 35, 56, 63 to Day and 84
Population: Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.
Secondary
Number of Participants With Exacerbations
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).
Time frame: Day 0 to Day 84
Population: Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.
Secondary
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
The FEV1 was maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.
Time frame: Day 0 to 84
Population: Data was not collected and hence, not analyzed for this outcome measure because the study was prematurely terminated on the basis of several factors namely, observed low rate of participant randomisation into the study; delay caused by temporary halt of study and potential for expiry date of investigation medicinal product before end of study.