Asthma
Conditions
Brief summary
Primary purpose is to assess if IMA-638 is safe and improves asthma in subjects with persistent asthma.
Interventions
BIOLOGICALIMA-638
SC Injection, 12 weeks
OTHERplacebo
placebo
Sponsors
Pfizer
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
* Generally healthy men and women with persistent asthma, 18 to 70 years of age, with body weight between 50 kg and 115 kg. * History of treatment with a medium to high dose of inhaled corticosteroids (ICS), with or without long-acting beta-agonists (LABA), for at least 2 months prior to the screening visit and must remain constant during the study. * FEV1 ≥ 55% to ≤ 80% predicted and demonstrated improvement in FEV1 (L) with inhaled albuterol (salbutamol) (reversibility) of ≥ 12%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Baseline, Day 112 | The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with the peak flow meter and instructed to perform the activity in triplicate in the morning prior to taking bronchodilator. The best among the 3 readings was selected. |
| Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 | Baseline, Day 112 | The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with the peak flow meter and instructed to perform the activity in triplicate in the morning prior to taking bronchodilator. The best among the 3 readings was selected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 1 | Baseline up to Day 112 | — |
| Forced Vital Capacity (FVC) - Stage 1 | Baseline, Day 8, 28, 56, 84, 112 | FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Forced Vital Capacity (FVC) - Stage 2/3 | Baseline, Day 8, 28, 56, 84, 112 | FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Forced Mid-Expiratory Flow Rate 25 Percent (%) to 75% (FEF25-75) - Stage 1 | Baseline, Day 8, 28, 56, 84, 112 | FEF25-75 is the average expiratory flow over the middle half of the FVC. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Forced Mid-Expiratory Flow Rate 25 Percent (%) to 75% (FEF25-75) - Stage 2/3 | Baseline, Day 8, 28, 56, 84, 112 | FEF25-75 is the average expiratory flow over the middle half of the FVC. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Blood Eosinophils Levels - Stage 1 | Baseline, Day 8, 28, 56, 84, 112 | — |
| Blood Eosinophils Levels - Stage 2/3 | Baseline, Day 8, 28, 56, 84, 112 | — |
| Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Baseline, Day 28, 56, 84, 112 | Log 10-transformed serum total IgE levels were expressed in Log-10 International units/milliliter (IU/mL). |
| Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Baseline, Day 28, 56, 84, 112 | Log 10-transformed serum total IgE levels were expressed in Log-10 International units/milliliter (IU/mL). |
| Serum Interleukin-13 (IL-13) Level - Stage 1 | Baseline, Day 8, 28, 56, 84, 112 | — |
| Serum Interleukin-13 (IL-13) Level - Stage 2/3 | Baseline, Day 8, 28, 56, 84, 112 | — |
| Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline, Day 8, 28, 56, 84, 112 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Participants performed the test in triplicate at each visit and the best of the 3 values was selected. |
| Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Baseline, Day 8, 28, 56, 84, 112 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Participants performed the test in triplicate at each visit and the best of the 3 values was selected. |
| Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 | Baseline, Day 28, 112 | Airway hyper-reactivity was assessed using provocative concentration 20 (PC20). PC20 was the concentration of methacholine at which participants had 20 percent (%) decrease in FEV1. Results for PC20 were summarized together for all participants who received any dose of IMA-638 and for all participants who received placebo during any stage of the study as per investigator's discretion. |
| Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline, Day 8, 28, 56, 84, 112 | ACQ-5 was a 5-item participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing). Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of less than or equal to (=\<) 0.75 indicate well-controlled asthma, scores between 0.76 and less than (\<) 1.5 indicate partly controlled asthma, and a score greater than or equal to (\>=) 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. |
| Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Baseline, Day 8, 28, 56, 84, 112 | ACQ-5 was a 5-item participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing). Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of =\< 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score \>= 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful. |
| Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 2/3 | Baseline up to Day 112 | — |
| Mean Number of Puffs of Rescue Medication Used - Stage 1 | Day 8, 28, 56, 84, 89, 91, 94, 98, 112 | The rescue medication taken for needed symptoms was a short acting beta agonist (SABA) inhaler. Albuterol, 90 microgram (mcg)/puff, was recommended for use. |
| Mean Number of Puffs of Rescue Medication Used - Stage 2/3 | Day 8, 28, 56, 84, 89, 91, 94, 98, 112 | The rescue medication taken for needed symptoms was a SABA inhaler. Albuterol, 90 mcg/puff, was recommended for use. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Important Changes in Physical Findings - Stage 2/3 | Baseline up to Day 112 | Physical examination included examination of general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts, abdomen, external genitalia, extremities, neurological exam, back/spine and lymph nodes. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 1 | Baseline up to Day 112 | Clinically significant ECG findings included - heart rate: \>15 bpm increase from baseline and \>=120 bpm, PR interval: \>=20 millisecond (msec) change from baseline and \>=220 msec: QRS interval: \>=120 msec: corrected QT (QTc) interval: \>450 msec for males and \>470 msec for females. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 2/3 | Baseline up to Day 112 | Clinically significant ECG findings included - heart rate: \>15 bpm increase from baseline and \>=120 bpm, PR interval: \>=20 msec change from baseline and \>=220 msec: QRS interval: \>=120 msec: QTc interval: \>450 msec for males and \>470 msec for females. |
| Number of Participants With Injection Site Reaction - Stage 1 | Baseline up to Day 112 | — |
| Number of Participants With Injection Site Reaction - Stage 2/3 | Baseline up to Day 112 | — |
| Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 1 | Baseline up to Day 112 | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils); hepatobiliary biochemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, gamma glutamyl transferase (GGT), total lactate dehydrogenase (LDH); renal function tests: blood urea nitrogen (BUN), creatinine, creatinine kinase, uric acid, albumin; electrolytes: sodium, potassium, calcium, magnesium, phosphorus; coagulation: prothrombin time and partial thromboplastin time; glucose: fasting, non-fasting; lipid profile: total cholesterol, triglycerides. |
| Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 2/3 | Baseline up to Day 112 | Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils); hepatobiliary biochemistry: ALT, AST, alkaline phosphatase, total bilirubin, GGT, total LDH; renal function tests: BUN, creatinine, creatinine kinase, uric acid, albumin; electrolytes: sodium, potassium, calcium, magnesium, phosphorus; coagulation: prothrombin time and partial thromboplastin time; glucose: fasting, non-fasting; lipid profile: total cholesterol, triglycerides. |
| Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance - Stage 2/3 | Baseline up to Day 112 | Criteria for PCI vital sign abnormalities- heart rate: \>15 bpm increase from baseline and \>=120 bpm, \>15 bpm decrease from baseline and \<=45 bpm: SBP: \>=20 mmHg increase from baseline and \>=160 mmHg, \>=20 mmHg decrease from baseline and \<=90 mmHg: DBP: of \>=15 mmHg increase from baseline and \>=100 mmHg, \>=15 mmHg decrease from baseline and \<=50 mmHg, oral temperature \<35 or \>38.3 degrees centigrade: respiratory rate: \<10 or \>25 breaths/minute: body weight: \>=7% increase or decrease from baseline. |
| Number of Participants With Clinically Important Changes in Physical Findings - Stage 1 | Baseline up to Day 112 | Physical examination included examination of general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts, abdomen, external genitalia, extremities, neurological exam, back/spine and lymph nodes. |
| Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance Stage 1 | Baseline up to Day 112 | Criteria for potentially clinically important (PCI) vital sign abnormalities- heart rate: greater than (\>) 15 beats per minute (bpm) increase from baseline and greater than or equal to (\>=) 120 bpm, \>15 bpm decrease from baseline and less than or equal to (\<=) 45 bpm: systolic blood pressure (SBP): \>=20 millimeter of mercury (mmHg) increase from baseline and \>=160 mmHg, \>=20 mmHg decrease from baseline and \<=90 mmHg: diastolic blood pressure (DBP): of \>=15 mmHg increase from baseline and \>=100 mmHg, \>=15 mmHg decrease from baseline and \<=50 mmHg, oral temperature \<35 or \>38.3 degrees centigrade: respiratory rate: \<10 or \>25 breaths/minute: body weight: \>=7% increase or decrease from baseline. |
Countries
Canada, United States
Participant flow
Pre-assignment details
This study had adaptive study design wherein participants were treated in 3 stages with higher number of participants enrolled in subsequent stages. As the treatment regimen was same for participants who received IMA-638 200 mg or placebo in Stage 2 and 3, participants were summarized together for these arms.
Participants by arm
| Arm | Count |
|---|---|
| IMA-638 0.2 mg/kg: Stage 1 IMA-638 0.2 milligram/kilogram (mg/kg) subcutaneous injection on Day 1, 8, 28, 56 and 84 during Stage 1. | 16 |
| IMA-638 0.6 mg/kg: Stage 1 IMA-638 0.6 mg/kg subcutaneous injection on Day 1, 8, 28, 56 and 84 during Stage 1. | 17 |
| IMA-638 2 mg/kg: Stage-1 IMA-638 2 mg/kg subcutaneous injection on Day 1, 8, 28, 56 and 84 during Stage 1. | 16 |
| Placebo: Stage 1 Placebo matched to IMA-638 subcutaneous injection on Day 1, 8, 28, 56 and 84 during Stage 1. | 16 |
| IMA-638 200 mg: Stage 2 and 3 IMA-638 200 milligram subcutaneous injection on Day 1, 8, 28, 42, 56, 70 and 84 during Stage 2 and 3. | 45 |
| IMA-638 75 mg: Stage 3 IMA-638 75 milligram subcutaneous injection on Day 1, 8, 28, 42, 56, 70 and 84 during Stage 3. | 4 |
| Placebo: Stage 2 and 3 Placebo matched to IMA-638 subcutaneous injection on Day 1, 8, 28, 42, 56, 70 and 84 during Stage 2 and 3. | 45 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 2 | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 3 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Sponsor's request | 0 | 0 | 0 | 0 | 19 | 4 | 15 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | IMA-638 2 mg/kg: Stage-1 | Placebo: Stage 1 | IMA-638 200 mg: Stage 2 and 3 | IMA-638 75 mg: Stage 3 | Placebo: Stage 2 and 3 | Total | IMA-638 0.2 mg/kg: Stage 1 | IMA-638 0.6 mg/kg: Stage 1 |
|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 71 years | 16 participants | 16 participants | 45 participants | 4 participants | 45 participants | 159 participants | 16 participants | 17 participants |
| Age, Customized Greater than 71 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized Less than 18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 25 Participants | 1 Participants | 28 Participants | 91 Participants | 11 Participants | 10 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 20 Participants | 3 Participants | 17 Participants | 68 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 16 | 12 / 17 | 11 / 16 | 10 / 16 | 27 / 45 | 1 / 4 | 26 / 45 |
| serious Total, serious adverse events | 0 / 16 | 1 / 17 | 2 / 16 | 1 / 16 | 2 / 45 | 0 / 4 | 0 / 45 |
Outcome results
Primary
Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1
The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with the peak flow meter and instructed to perform the activity in triplicate in the morning prior to taking bronchodilator. The best among the 3 readings was selected.
Time frame: Baseline, Day 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1. Last observation carried forward (LOCF) method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Baseline | 286.4 liter per minute (L/min) | Standard Deviation 67.6 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Change at Day 112 | 21.1 liter per minute (L/min) | Standard Deviation 40.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Change at Day 112 | 3.4 liter per minute (L/min) | Standard Deviation 53.6 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Baseline | 297.6 liter per minute (L/min) | Standard Deviation 55.4 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Baseline | 343.5 liter per minute (L/min) | Standard Deviation 91.8 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Change at Day 112 | 7.6 liter per minute (L/min) | Standard Deviation 38.1 |
| Placebo: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Baseline | 291.5 liter per minute (L/min) | Standard Deviation 64.7 |
| Placebo: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 1 | Change at Day 112 | 11.8 liter per minute (L/min) | Standard Deviation 37.5 |
Primary
Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3
The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with the peak flow meter and instructed to perform the activity in triplicate in the morning prior to taking bronchodilator. The best among the 3 readings was selected.
Time frame: Baseline, Day 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3. LOCF method was used to impute missing values. n signifies those participants who were evaluated for this measure at the specified time point for each arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 | Baseline (n=42, 4, 45) | 329.3 L/min | Standard Deviation 81.7 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 | Change at Day 112 (n=45, 4, 45) | 6.8 L/min | Standard Deviation 42.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 | Baseline (n=42, 4, 45) | 348.6 L/min | Standard Deviation 39.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 | Change at Day 112 (n=45, 4, 45) | 18.8 L/min | Standard Deviation 30.7 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 | Baseline (n=42, 4, 45) | 330.4 L/min | Standard Deviation 89.5 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Morning (Ante Meridiem) Peak Expiratory Flow Rate (AM PEFR) at Day 112 - Stage 2/3 | Change at Day 112 (n=45, 4, 45) | 7.6 L/min | Standard Deviation 48.9 |
Comparison: Day 112: Analysis of co-variance (ANCOVA) model was used with baseline as a covariate, long-acting beta-agonist (LABA) use (Inhaled Corticosteroid \[ICS\] only or ICS plus LABA) and treatment as two factors.p-value: 0.61295% CI: [-25.6, 15.2]ANCOVA
Secondary
Blood Eosinophils Levels - Stage 1
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Baseline | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 8 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 28 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.3 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 56 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 84 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 112 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 112 | 0.4 10^9 cells per liter (cells/L) | Standard Deviation 0.3 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 56 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.3 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Baseline | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 28 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.4 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 8 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 84 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.3 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 1 | Day 8 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 1 | Day 28 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 1 | Day 56 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 1 | Day 112 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 1 | Day 84 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 1 | Baseline | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| Placebo: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 84 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| Placebo: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 112 | 0.2 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| Placebo: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 8 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| Placebo: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 56 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.1 |
| Placebo: Stage 1 | Blood Eosinophils Levels - Stage 1 | Baseline | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.2 |
| Placebo: Stage 1 | Blood Eosinophils Levels - Stage 1 | Day 28 | 0.3 10^9 cells per liter (cells/L) | Standard Deviation 0.1 |
Secondary
Blood Eosinophils Levels - Stage 2/3
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Baseline | 0.3 10^9 cells/L | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 8 | 0.3 10^9 cells/L | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 28 | 0.3 10^9 cells/L | Standard Deviation 0.3 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 56 | 0.3 10^9 cells/L | Standard Deviation 0.3 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 84 | 0.3 10^9 cells/L | Standard Deviation 0.3 |
| IMA-638 0.2 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 112 | 0.3 10^9 cells/L | Standard Deviation 0.4 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 112 | 0.8 10^9 cells/L | Standard Deviation 0.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Baseline | 0.7 10^9 cells/L | Standard Deviation 1 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 56 | 0.8 10^9 cells/L | Standard Deviation 0.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 84 | 0.8 10^9 cells/L | Standard Deviation 0.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 8 | 0.7 10^9 cells/L | Standard Deviation 1 |
| IMA-638 0.6 mg/kg: Stage 1 | Blood Eosinophils Levels - Stage 2/3 | Day 28 | 0.8 10^9 cells/L | Standard Deviation 0.9 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 2/3 | Day 8 | 0.3 10^9 cells/L | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 2/3 | Day 28 | 0.3 10^9 cells/L | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 2/3 | Day 112 | 0.2 10^9 cells/L | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 2/3 | Day 56 | 0.3 10^9 cells/L | Standard Deviation 0.1 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 2/3 | Baseline | 0.3 10^9 cells/L | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Blood Eosinophils Levels - Stage 2/3 | Day 84 | 0.2 10^9 cells/L | Standard Deviation 0.1 |
Secondary
Change From Baseline in Airway Hyper-reactivity at Day 28 and 112
Airway hyper-reactivity was assessed using provocative concentration 20 (PC20). PC20 was the concentration of methacholine at which participants had 20 percent (%) decrease in FEV1. Results for PC20 were summarized together for all participants who received any dose of IMA-638 and for all participants who received placebo during any stage of the study as per investigator's discretion.
Time frame: Baseline, Day 28, 112
Population: mITT population included all randomized participants who received at least 1 dose administration of the test article. LOCF method was used to impute missing values. 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 | Baseline | 1.1 milligram per milliliter (mg/mL) | Standard Deviation 13.8 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 | Change at Day 28 | 1.2 milligram per milliliter (mg/mL) | Standard Deviation 9.8 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 | Change at Day 112 | 1.0 milligram per milliliter (mg/mL) | Standard Deviation 28.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 | Baseline | 0.3 milligram per milliliter (mg/mL) | Standard Deviation 38.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 | Change at Day 28 | 0.6 milligram per milliliter (mg/mL) | Standard Deviation 11.4 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Airway Hyper-reactivity at Day 28 and 112 | Change at Day 112 | 0.5 milligram per milliliter (mg/mL) | Standard Deviation 22.7 |
Comparison: Day 28: ANCOVA model was based on the log 2 transformed methacholine challenge test values with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.0995% CI: [-0.3, 3.9]ANCOVA
Comparison: Day 112: ANCOVA model was based on the log 2 transformed methacholine challenge test values with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.14495% CI: [-0.8, 5]ANCOVA
Secondary
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1
ACQ-5 was a 5-item participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing). Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of less than or equal to (=\<) 0.75 indicate well-controlled asthma, scores between 0.76 and less than (\<) 1.5 indicate partly controlled asthma, and a score greater than or equal to (\>=) 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline | 2.7 units on a scale | Standard Deviation 0.6 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 8 | -0.6 units on a scale | Standard Deviation 1.1 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 28 | -0.7 units on a scale | Standard Deviation 1.1 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 56 | -0.8 units on a scale | Standard Deviation 1.1 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 84 | -1.1 units on a scale | Standard Deviation 1.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 112 | -0.9 units on a scale | Standard Deviation 1.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 112 | -0.7 units on a scale | Standard Deviation 0.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 56 | -0.6 units on a scale | Standard Deviation 0.8 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline | 2.6 units on a scale | Standard Deviation 0.8 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 28 | -0.5 units on a scale | Standard Deviation 0.7 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 8 | -0.2 units on a scale | Standard Deviation 0.7 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 84 | -0.8 units on a scale | Standard Deviation 0.9 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 8 | -0.6 units on a scale | Standard Deviation 0.7 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 28 | -0.8 units on a scale | Standard Deviation 0.9 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 56 | -1.1 units on a scale | Standard Deviation 1.1 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 112 | -1.2 units on a scale | Standard Deviation 1 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 84 | -1.1 units on a scale | Standard Deviation 1.1 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline | 2.8 units on a scale | Standard Deviation 0.6 |
| Placebo: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 84 | -0.8 units on a scale | Standard Deviation 0.8 |
| Placebo: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 112 | -0.8 units on a scale | Standard Deviation 0.8 |
| Placebo: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 8 | -0.3 units on a scale | Standard Deviation 0.6 |
| Placebo: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 56 | -0.7 units on a scale | Standard Deviation 0.7 |
| Placebo: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline | 2.7 units on a scale | Standard Deviation 0.7 |
| Placebo: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 28 | -0.7 units on a scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3
ACQ-5 was a 5-item participant-reported questionnaire assessing asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing). Participants were asked to recall how their asthma had been during the previous week. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of =\< 0.75 indicate well-controlled asthma, scores between 0.76 and \< 1.5 indicate partly controlled asthma, and a score \>= 1.5 indicates uncontrolled asthma. Individual changes of at least 0.5 are considered to be clinically meaningful.
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Baseline | 2.7 units on a scale | Standard Deviation 0.6 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 8 | -0.6 units on a scale | Standard Deviation 0.7 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 28 | -0.7 units on a scale | Standard Deviation 1 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 56 | -0.8 units on a scale | Standard Deviation 1.1 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 84 | -0.8 units on a scale | Standard Deviation 1.1 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 112 | -0.8 units on a scale | Standard Deviation 1.1 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 112 | -0.4 units on a scale | Standard Deviation 0.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Baseline | 2.3 units on a scale | Standard Deviation 0.6 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 56 | -0.4 units on a scale | Standard Deviation 0.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 84 | -0.4 units on a scale | Standard Deviation 0.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 8 | -0.4 units on a scale | Standard Deviation 0.8 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 28 | -0.4 units on a scale | Standard Deviation 0.9 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 8 | -0.5 units on a scale | Standard Deviation 0.7 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 28 | -0.7 units on a scale | Standard Deviation 0.8 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 112 | -1.0 units on a scale | Standard Deviation 0.9 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 56 | -0.8 units on a scale | Standard Deviation 0.9 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Baseline | 2.8 units on a scale | Standard Deviation 0.6 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 84 | -1.0 units on a scale | Standard Deviation 0.9 |
Comparison: Day 8: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.35495% CI: [-0.4, 0.1]ANCOVA
Comparison: Day 28: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.995% CI: [-0.4, 0.4]ANCOVA
Comparison: Day 56: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.92195% CI: [-0.4, 0.4]ANCOVA
Comparison: Day 84: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.38895% CI: [-0.2, 0.6]ANCOVA
Comparison: Day 112: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.24995% CI: [-0.2, 0.7]ANCOVA
Secondary
Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1
FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Participants performed the test in triplicate at each visit and the best of the 3 values was selected.
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline | 2.1 liter | Standard Deviation 0.4 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 8 | 0.1 liter | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 28 | 0.1 liter | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 56 | 0.0 liter | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 84 | 0.1 liter | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 112 | 0.2 liter | Standard Deviation 0.3 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 112 | 0.1 liter | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 56 | 0.1 liter | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline | 2.0 liter | Standard Deviation 0.4 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 28 | 0.1 liter | Standard Deviation 0.1 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 8 | 0.0 liter | Standard Deviation 0.1 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 84 | 0.0 liter | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 8 | 0.0 liter | Standard Deviation 0.3 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 28 | 0.0 liter | Standard Deviation 0.4 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 56 | 0.1 liter | Standard Deviation 0.3 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 112 | 0.1 liter | Standard Deviation 0.4 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 84 | 0.0 liter | Standard Deviation 0.4 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline | 2.3 liter | Standard Deviation 0.5 |
| Placebo: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 84 | 0.1 liter | Standard Deviation 0.2 |
| Placebo: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 112 | 0.1 liter | Standard Deviation 0.3 |
| Placebo: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 8 | -0.0 liter | Standard Deviation 0.2 |
| Placebo: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 56 | 0.1 liter | Standard Deviation 0.2 |
| Placebo: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Baseline | 2.0 liter | Standard Deviation 0.5 |
| Placebo: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 1 | Change at Day 28 | 0.0 liter | Standard Deviation 0.2 |
Secondary
Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3
FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Participants performed the test in triplicate at each visit and the best of the 3 values was selected.
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3. LOCF method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Baseline | 2.2 liter | Standard Deviation 0.6 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 8 | -0.0 liter | Standard Deviation 0.2 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 28 | 0.0 liter | Standard Deviation 0.3 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 56 | 0.0 liter | Standard Deviation 0.3 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 84 | 0.1 liter | Standard Deviation 0.3 |
| IMA-638 0.2 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 112 | 0.1 liter | Standard Deviation 0.3 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 112 | 0.2 liter | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Baseline | 2.3 liter | Standard Deviation 0.7 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 56 | 0.2 liter | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 84 | 0.2 liter | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 8 | 0.2 liter | Standard Deviation 0.2 |
| IMA-638 0.6 mg/kg: Stage 1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 28 | 0.2 liter | Standard Deviation 0.2 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 8 | 0.0 liter | Standard Deviation 0.3 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 28 | 0.1 liter | Standard Deviation 0.3 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 112 | 0.1 liter | Standard Deviation 0.3 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 56 | 0.1 liter | Standard Deviation 0.3 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Baseline | 2.1 liter | Standard Deviation 0.6 |
| IMA-638 2 mg/kg: Stage-1 | Change From Baseline in Pre-beta-agonist Forced Expiratory Volume in 1 Second (FEV1) at Day 8, 28, 56, 84 and 112 - Stage 2/3 | Change at Day 84 | 0.1 liter | Standard Deviation 0.3 |
Comparison: Day 8: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.48295% CI: [-0.2, 0.1]ANCOVA
Comparison: Day 28: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.49295% CI: [-0.2, 0.1]ANCOVA
Comparison: Day 56: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.32395% CI: [-0.2, 0.1]ANCOVA
Comparison: Day 84: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.22695% CI: [-0.2, 0.1]ANCOVA
Comparison: Day 112: ANCOVA model was used with baseline as a covariate, LABA use (ICS only or ICS plus LABA) and treatment as two factors.p-value: 0.25695% CI: [-0.2, 0.1]ANCOVA
Secondary
Forced Mid-Expiratory Flow Rate 25 Percent (%) to 75% (FEF25-75) - Stage 1
FEF25-75 is the average expiratory flow over the middle half of the FVC. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: Data for this outcome measure was not analyzed as the study was stopped early and sponsor's decision to analyze only safety and key efficacy outcomes.
Secondary
Forced Mid-Expiratory Flow Rate 25 Percent (%) to 75% (FEF25-75) - Stage 2/3
FEF25-75 is the average expiratory flow over the middle half of the FVC. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: Data for this outcome measure was not analyzed as the study was stopped early and sponsor's decision to analyze only safety and key efficacy outcomes.
Secondary
Forced Vital Capacity (FVC) - Stage 1
FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: Data for this outcome measure was not analyzed as the study was stopped early and sponsor's decision to analyze only safety and key efficacy outcomes.
Secondary
Forced Vital Capacity (FVC) - Stage 2/3
FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: Data for this outcome measure was not analyzed as the study was stopped early and sponsor's decision to analyze only safety and key efficacy outcomes.
Secondary
Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1
Log 10-transformed serum total IgE levels were expressed in Log-10 International units/milliliter (IU/mL).
Time frame: Baseline, Day 28, 56, 84, 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose of test article in Stage 1. LOCF method was used to impute missing values.'N' (Number of Participants Analyzed) signifies participants evaluable for this measure.n signifies participants evaluated for this measure at the specified time point for each arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 84 (n=16, 17, 16, 16) | 3.8 log-10 IU/mL | Standard Deviation 1.6 |
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 28 (n=16, 17, 16, 16) | 3.8 log-10 IU/mL | Standard Deviation 1.5 |
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 112 (n=16, 17, 16, 16) | 3.8 log-10 IU/mL | Standard Deviation 1.6 |
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 56 (n=16, 17, 16, 16) | 3.7 log-10 IU/mL | Standard Deviation 1.7 |
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Baseline (n=16, 16, 14, 14) | 3.8 log-10 IU/mL | Standard Deviation 1.6 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 56 (n=16, 17, 16, 16) | 4.2 log-10 IU/mL | Standard Deviation 1.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 84 (n=16, 17, 16, 16) | 4.2 log-10 IU/mL | Standard Deviation 1.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 112 (n=16, 17, 16, 16) | 4.1 log-10 IU/mL | Standard Deviation 1.7 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 28 (n=16, 17, 16, 16) | 4.3 log-10 IU/mL | Standard Deviation 1.9 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Baseline (n=16, 16, 14, 14) | 4.5 log-10 IU/mL | Standard Deviation 1.9 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 56 (n=16, 17, 16, 16) | 4.3 log-10 IU/mL | Standard Deviation 1.5 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Baseline (n=16, 16, 14, 14) | 4.4 log-10 IU/mL | Standard Deviation 1.4 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 28 (n=16, 17, 16, 16) | 4.5 log-10 IU/mL | Standard Deviation 1.4 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 84 (n=16, 17, 16, 16) | 4.4 log-10 IU/mL | Standard Deviation 1.5 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 112 (n=16, 17, 16, 16) | 4.3 log-10 IU/mL | Standard Deviation 1.5 |
| Placebo: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 84 (n=16, 17, 16, 16) | 4.6 log-10 IU/mL | Standard Deviation 1.7 |
| Placebo: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 28 (n=16, 17, 16, 16) | 4.5 log-10 IU/mL | Standard Deviation 1.7 |
| Placebo: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Baseline (n=16, 16, 14, 14) | 4.9 log-10 IU/mL | Standard Deviation 1.4 |
| Placebo: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 56 (n=16, 17, 16, 16) | 4.6 log-10 IU/mL | Standard Deviation 1.7 |
| Placebo: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 1 | Day 112 (n=16, 17, 16, 16) | 4.6 log-10 IU/mL | Standard Deviation 1.7 |
Secondary
Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3
Log 10-transformed serum total IgE levels were expressed in Log-10 International units/milliliter (IU/mL).
Time frame: Baseline, Day 28, 56, 84, 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3. LOCF method was used to impute missing values. n signifies participants evaluated for this measure at the specified time point for each arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 84 (n=45, 4, 45) | 4.6 log-10 IU/mL | Standard Deviation 1.5 |
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 56 (n=45, 4, 45) | 4.6 log-10 IU/mL | Standard Deviation 1.5 |
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Baseline (n=43, 4, 43) | 4.5 log-10 IU/mL | Standard Deviation 1.5 |
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 28 (n=44, 4, 45) | 4.6 log-10 IU/mL | Standard Deviation 1.5 |
| IMA-638 0.2 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 112 (n=45, 4, 45) | 4.6 log-10 IU/mL | Standard Deviation 1.5 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 56 (n=45, 4, 45) | 5.1 log-10 IU/mL | Standard Deviation 1.8 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Baseline (n=43, 4, 43) | 5.1 log-10 IU/mL | Standard Deviation 1.7 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 28 (n=44, 4, 45) | 5.1 log-10 IU/mL | Standard Deviation 1.8 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 84 (n=45, 4, 45) | 5.1 log-10 IU/mL | Standard Deviation 1.8 |
| IMA-638 0.6 mg/kg: Stage 1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 112 (n=45, 4, 45) | 5.1 log-10 IU/mL | Standard Deviation 1.8 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 112 (n=45, 4, 45) | 5.0 log-10 IU/mL | Standard Deviation 1.2 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 84 (n=45, 4, 45) | 4.9 log-10 IU/mL | Standard Deviation 1.2 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Baseline (n=43, 4, 43) | 4.9 log-10 IU/mL | Standard Deviation 1.2 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 56 (n=45, 4, 45) | 4.9 log-10 IU/mL | Standard Deviation 1.2 |
| IMA-638 2 mg/kg: Stage-1 | Log 10-transformed Serum Total Immunoglobulin E (IgE) Levels - Stage 2/3 | Day 28 (n=44, 4, 45) | 4.9 log-10 IU/mL | Standard Deviation 1.3 |
Secondary
Mean Number of Puffs of Rescue Medication Used - Stage 1
The rescue medication taken for needed symptoms was a short acting beta agonist (SABA) inhaler. Albuterol, 90 microgram (mcg)/puff, was recommended for use.
Time frame: Day 8, 28, 56, 84, 89, 91, 94, 98, 112
Population: Data for this outcome measure was not analyzed as the study was stopped early and sponsor's decision to analyze only safety and key efficacy outcomes.
Secondary
Mean Number of Puffs of Rescue Medication Used - Stage 2/3
The rescue medication taken for needed symptoms was a SABA inhaler. Albuterol, 90 mcg/puff, was recommended for use.
Time frame: Day 8, 28, 56, 84, 89, 91, 94, 98, 112
Population: Data for this outcome measure was not analyzed as the study was stopped early and sponsor's decision to analyze only safety and key efficacy outcomes.
Secondary
Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 1
Time frame: Baseline up to Day 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1. LOCF method was used to impute missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 1 | 0.00 percentage of participants |
| IMA-638 0.6 mg/kg: Stage 1 | Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 1 | 0.00 percentage of participants |
| IMA-638 2 mg/kg: Stage-1 | Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 1 | 6.25 percentage of participants |
| Placebo: Stage 1 | Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 1 | 12.50 percentage of participants |
p-value: 0.267Chi-squared
Secondary
Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 2/3
Time frame: Baseline up to Day 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3. LOCF method was used to impute missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 2/3 | 11.11 percentage of participant |
| IMA-638 0.6 mg/kg: Stage 1 | Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 2/3 | 25.00 percentage of participant |
| IMA-638 2 mg/kg: Stage-1 | Percentage of Participants Who Required Treatment With Systemic Steroids for Clinical Exacerbation of Asthma - Stage 2/3 | 0.00 percentage of participant |
p-value: 0.029Chi-squared
Secondary
Serum Interleukin-13 (IL-13) Level - Stage 1
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: Data for this outcome measure was not analyzed as the study was stopped early and sponsor's decision to analyze only safety and key efficacy outcomes.
Secondary
Serum Interleukin-13 (IL-13) Level - Stage 2/3
Time frame: Baseline, Day 8, 28, 56, 84, 112
Population: Data for this outcome measure was not analyzed as the study was stopped early and sponsor's decision to analyze only safety and key efficacy outcomes.
Other Pre-specified
Number of Participants With Clinically Important Changes in Physical Findings - Stage 1
Physical examination included examination of general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts, abdomen, external genitalia, extremities, neurological exam, back/spine and lymph nodes.
Time frame: Baseline up to Day 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Clinically Important Changes in Physical Findings - Stage 1 | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Clinically Important Changes in Physical Findings - Stage 1 | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Clinically Important Changes in Physical Findings - Stage 1 | 0 participants |
| Placebo: Stage 1 | Number of Participants With Clinically Important Changes in Physical Findings - Stage 1 | 0 participants |
Other Pre-specified
Number of Participants With Clinically Important Changes in Physical Findings - Stage 2/3
Physical examination included examination of general appearance, skin, head, ears, eyes, nose, throat, heart, lungs, breasts, abdomen, external genitalia, extremities, neurological exam, back/spine and lymph nodes.
Time frame: Baseline up to Day 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Clinically Important Changes in Physical Findings - Stage 2/3 | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Clinically Important Changes in Physical Findings - Stage 2/3 | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Clinically Important Changes in Physical Findings - Stage 2/3 | 0 participants |
Other Pre-specified
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 1
Clinically significant ECG findings included - heart rate: \>15 bpm increase from baseline and \>=120 bpm, PR interval: \>=20 millisecond (msec) change from baseline and \>=220 msec: QRS interval: \>=120 msec: corrected QT (QTc) interval: \>450 msec for males and \>470 msec for females.
Time frame: Baseline up to Day 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 1 | 1 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 1 | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 1 | 1 participants |
| Placebo: Stage 1 | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 1 | 1 participants |
Other Pre-specified
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 2/3
Clinically significant ECG findings included - heart rate: \>15 bpm increase from baseline and \>=120 bpm, PR interval: \>=20 msec change from baseline and \>=220 msec: QRS interval: \>=120 msec: QTc interval: \>450 msec for males and \>470 msec for females.
Time frame: Baseline up to Day 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 2/3 | 3 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 2/3 | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern - Stage 2/3 | 1 participants |
Other Pre-specified
Number of Participants With Injection Site Reaction - Stage 1
Time frame: Baseline up to Day 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site bruising | 1 participants |
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site erythema | 0 participants |
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site swelling | 0 participants |
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site urticaria | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site erythema | 1 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site urticaria | 1 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site bruising | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site swelling | 1 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site swelling | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site urticaria | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site bruising | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site erythema | 0 participants |
| Placebo: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site urticaria | 0 participants |
| Placebo: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site bruising | 0 participants |
| Placebo: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site erythema | 0 participants |
| Placebo: Stage 1 | Number of Participants With Injection Site Reaction - Stage 1 | Injection site swelling | 0 participants |
Other Pre-specified
Number of Participants With Injection Site Reaction - Stage 2/3
Time frame: Baseline up to Day 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site swelling | 0 participants |
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site induration | 0 participants |
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site bruising | 1 participants |
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site erythema | 2 participants |
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site urticaria | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site induration | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site bruising | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site erythema | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site swelling | 0 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site urticaria | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site urticaria | 1 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site swelling | 1 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site bruising | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site induration | 1 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Injection Site Reaction - Stage 2/3 | Injection site erythema | 1 participants |
Other Pre-specified
Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 1
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils); hepatobiliary biochemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, gamma glutamyl transferase (GGT), total lactate dehydrogenase (LDH); renal function tests: blood urea nitrogen (BUN), creatinine, creatinine kinase, uric acid, albumin; electrolytes: sodium, potassium, calcium, magnesium, phosphorus; coagulation: prothrombin time and partial thromboplastin time; glucose: fasting, non-fasting; lipid profile: total cholesterol, triglycerides.
Time frame: Baseline up to Day 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 1 | 5 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 1 | 11 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 1 | 12 participants |
| Placebo: Stage 1 | Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 1 | 9 participants |
Other Pre-specified
Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 2/3
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils); hepatobiliary biochemistry: ALT, AST, alkaline phosphatase, total bilirubin, GGT, total LDH; renal function tests: BUN, creatinine, creatinine kinase, uric acid, albumin; electrolytes: sodium, potassium, calcium, magnesium, phosphorus; coagulation: prothrombin time and partial thromboplastin time; glucose: fasting, non-fasting; lipid profile: total cholesterol, triglycerides.
Time frame: Baseline up to Day 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3. LOCF method was used to impute missing values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 2/3 | 30 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 2/3 | 1 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Laboratory Test Abnormalities of Potential Clinical Importance - Stage 2/3 | 21 participants |
Other Pre-specified
Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance Stage 1
Criteria for potentially clinically important (PCI) vital sign abnormalities- heart rate: greater than (\>) 15 beats per minute (bpm) increase from baseline and greater than or equal to (\>=) 120 bpm, \>15 bpm decrease from baseline and less than or equal to (\<=) 45 bpm: systolic blood pressure (SBP): \>=20 millimeter of mercury (mmHg) increase from baseline and \>=160 mmHg, \>=20 mmHg decrease from baseline and \<=90 mmHg: diastolic blood pressure (DBP): of \>=15 mmHg increase from baseline and \>=100 mmHg, \>=15 mmHg decrease from baseline and \<=50 mmHg, oral temperature \<35 or \>38.3 degrees centigrade: respiratory rate: \<10 or \>25 breaths/minute: body weight: \>=7% increase or decrease from baseline.
Time frame: Baseline up to Day 112
Population: mITT population (Stage 1) included all randomized participants who received at least 1 dose administration of the test article in Stage 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance Stage 1 | 1 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance Stage 1 | 2 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance Stage 1 | 1 participants |
| Placebo: Stage 1 | Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance Stage 1 | 1 participants |
Other Pre-specified
Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance - Stage 2/3
Criteria for PCI vital sign abnormalities- heart rate: \>15 bpm increase from baseline and \>=120 bpm, \>15 bpm decrease from baseline and \<=45 bpm: SBP: \>=20 mmHg increase from baseline and \>=160 mmHg, \>=20 mmHg decrease from baseline and \<=90 mmHg: DBP: of \>=15 mmHg increase from baseline and \>=100 mmHg, \>=15 mmHg decrease from baseline and \<=50 mmHg, oral temperature \<35 or \>38.3 degrees centigrade: respiratory rate: \<10 or \>25 breaths/minute: body weight: \>=7% increase or decrease from baseline.
Time frame: Baseline up to Day 112
Population: mITT population (Stage 2 and 3) included all randomized participants who received at least 1 dose administration of the test article in Stage 2 and 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMA-638 0.2 mg/kg: Stage 1 | Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance - Stage 2/3 | 3 participants |
| IMA-638 0.6 mg/kg: Stage 1 | Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance - Stage 2/3 | 0 participants |
| IMA-638 2 mg/kg: Stage-1 | Number of Participants With Vital Sign Abnormalities of Potential Clinical Importance - Stage 2/3 | 1 participants |