Asthma
Conditions
Brief summary
This is a Phase IIa, randomized, placebo-controlled, double-blind, multicenter, two-arm study to evaluate the efficacy, safety, and pharmacokinetics of MTPS9579A as an add-on therapy in patients with uncontrolled moderate to severe asthma who are receiving daily ICS therapy and at least one of the following additional controller medications: long-acting beta-agonist (LABA), leukotriene modulator (leukotriene modifier \[LTM\] or leukotriene receptor antagonist \[LTRA\]), long-acting muscarinic antagonist (LAMA), or long-acting theophylline preparation.
Interventions
DRUGMTPS9579A
MTPS9579A IV infusion will be administered at the randomization visit (Week 2), Week 6, and every 4 weeks through Week 46.
DRUGPlacebo
Placebo matching MTPS9579A will be administered at the randomization visit (Week 2), Week 6, and every 4 weeks thereafter through Week 46.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Documented physician-diagnosed asthma for at least 12 months prior to screening * Treatment with asthma controller therapy (daily ICS \[fluticasone propionate or equivalent\] and at least one additional controller therapy \[LABA, LAMA, LTM/LTRA\]) for \>= 3 months prior to screening, with no changes within 4 weeks prior to screening or during the screening period and no anticipated changes in controller dosing regimens throughout the study * Documented history of \>= 2 asthma exacerbation within the 12 months prior to screening while on daily ICS maintenance therapy * For women of childbearing potential: agreement to remain abstinent or use contraception For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm
Exclusion criteria
* History or evidence of vocal cord dysfunction, reactive airways dysfunction syndrome, hyperventilation associated with panic attacks, or other mimics of asthma * History or evidence of significant respiratory disease other than asthma, including occupational asthma, aspirin-sensitive asthma, asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome, bronchiolitis, interstitial lung disease, or COPD * Current smoker, electronic cigarette (e-cigarette) user, former smoker with smoking history of \> 10 pack-years, former e-cigarette user with an e-cigarette history of at least daily use for \>=10 years, or unwilling to abstain from smoking and/or e-cigarette use from the time of consent through the completion of the study * History or evidence of any clinically significant medical condition/disease or abnormalities in laboratory tests that, in the investigator's judgment, precludes the patient's safe participation and completion of the study, or interferes with the conduct and interpretation of the study * Active malignancy or history of malignancy within 5 years of screening, except for appropriately treated non-melanoma skin carcinoma, cervical carcinoma in situ, breast ductal carcinoma in situ, or Stage I uterine cancer * Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of MTPS9579A * Positive for TB at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Composite Asthma Exacerbations (CompEX) Event | Randomization [Week 2] to end of treatment (EOT) [Week 50] | CompEX is defined as time from randomization to first asthma exacerbation or diary worsening during the treatment period. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Diary worsening is based on the occurrence of prespecified changes in the following six parameters: morning peak expiratory flow rate (PEFR), evening PEFR, morning symptom score, evening symptom score, morning short-acting rescue therapy use, and evening short-acting rescue therapy use. Hazard ratio was used for the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Asthma Exacerbations | Randomization [Week 2] to Week 50 | The number of asthma exacerbations per year was reported for this outcome measure. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Poisson regression was used for the analysis. |
| Time to First Asthma Exacerbation | Randomization [Week 2] to Week 50 | The time from randomization to first asthma exacerbation was measured. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Cox regression was used for the analysis. |
| Absolute Change From Randomization in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 50 | Randomization [Week 2] to Week 50 | FEV1 is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FEV1 as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FEV1 as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/microliter (uL)), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or \>=2 events), and geographic region. |
| Relative Percent Change From Randomization in Pre-Bronchodilator FEV1 at Week 50 | Randomization [Week 2] to Week 50 | FEV1 was the volume of air exhaled in the first second of a forced exhalation as measured by spirometer. Measurements were performed before use of bronchodilator. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the relative change pre-bronchodilator FEV1 as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FEV1 as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or \>=2 events), and geographic region. Relative change (%) in FEV1 = (absolute change in FEV1 / baseline FEV1) x 100. |
| Absolute Change From Randomization in Fractional Exhaled Nitric Oxide (FeNO) at Week 50 | Randomization [Week 2] to Week 50 | FeNO is a volatile marker of airway inflammation that decreases with inhaled corticosteroid treatment. The measurements recorded were according to standardized procedures by the American Thoracic Society. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FeNO as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FeNO as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or \>=2 events), and geographic region. |
| Relative Percent Change From Randomization in FeNO at Week 50 | Randomization [Week 2] to Week 50 | FeNO is a volatile marker of airway inflammation that decreases with inhaled corticosteroid treatment. The measurements recorded were according to standardized procedures by the American Thoracic Society. Relative change (%) in FeNO = (absolute change in FeNO / baseline FeNO) x 100. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FeNO as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FeNO as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or \>=2 events), and geographic region. |
| Percentage of Participants With Adverse Events | Up to approximately Week 58 | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. |
| Area Under Concentration-Time Curve for the First Dosing Interval (AUClast) of MTPS9579A | Randomization [Week 2] to Week 6 | — |
| Maximum Serum Concentration (Cmax) for the First Dosing Interval of MTPS9579A | 2-hour post-dose on Week 2 | — |
| Steady State Cmax of MTPS9579A | 2-hour post-dose on Week 14 | — |
| Maximum Time to Serum Concentration (Tmax) of MTPS9579A | Pre-dose and 2-hour post-dose on Week 2 | — |
| Trough Serum Concentration (Ctrough) Accumulation Ratio of MTPS9579A | Predose on Weeks 6 and 14 | The accumulation ratio is calculated by taking the individual ratio of the Ctrough at Week 14 to the Ctrough at Week 6. |
| Steady State Ctrough of MTPS9579A | Pre-dose on Week 14 | — |
| Percentage of Participants With Anti-Drug Antibodies (ADA) to MTPS9579A | Pre-dose Week 54 | Treatment Emergent ADA is (a) negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, OR (b) positive ADA result at baseline and one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. |
Countries
Argentina, Germany, Peru, Poland, United States
Participant flow
Recruitment details
Participants took part in the study at 26 investigative sites in 5 countries (Argentina, Germany, Peru, Poland, and the United States) from 31 October 2019 to 19 May 2022.
Pre-assignment details
This study included a 2-week single-blind placebo run-in period. A total of 135 participants were randomized in double-blind treatment period. Of the 135 participants randomized, 134 participants received at least one dose of study drug and their intended treatment.
Participants by arm
| Arm | Count |
|---|---|
| MTPS9579A, 1800 mg Participants with uncontrolled moderate to severe asthma received Placebo, given as IV infusion, for 14 days in the Placebo run-in period. Participants then received MTPS9579A,1800 mg, given as IV infusion at randomization (Week 2), Week 6, and every 4 weeks thereafter through Week 46. | 69 |
| Placebo Participants with uncontrolled moderate to severe asthma received Placebo, given as IV infusion, for 14 days in the Placebo run-in period. Participants received MTPS9579A matching placebo, given as IV infusion at randomization (Week 2), Week 6, and every 4 weeks thereafter through Week 46. | 65 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Enrolled but Failed to Meet Randomization Criteria; Excluded from Study Analysis | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | MTPS9579A, 1800 mg |
|---|---|---|---|
| Age, Continuous | 52.9 years STANDARD_DEVIATION 13.2 | 53.8 years STANDARD_DEVIATION 12.6 | 54.7 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 22 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 112 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) White | 59 Participants | 121 Participants | 62 Participants |
| Sex: Female, Male Female | 34 Participants | 73 Participants | 39 Participants |
| Sex: Female, Male Male | 31 Participants | 61 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 69 | 1 / 66 |
| other Total, other adverse events | 32 / 69 | 38 / 65 |
| serious Total, serious adverse events | 5 / 69 | 4 / 65 |
Outcome results
Primary
Time to First Composite Asthma Exacerbations (CompEX) Event
CompEX is defined as time from randomization to first asthma exacerbation or diary worsening during the treatment period. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Diary worsening is based on the occurrence of prespecified changes in the following six parameters: morning peak expiratory flow rate (PEFR), evening PEFR, morning symptom score, evening symptom score, morning short-acting rescue therapy use, and evening short-acting rescue therapy use. Hazard ratio was used for the analysis.
Time frame: Randomization [Week 2] to end of treatment (EOT) [Week 50]
Population: Modified Intent-to-Treat population (mITT) population included all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MTPS9579A, 1800 mg | Time to First Composite Asthma Exacerbations (CompEX) Event | NA weeks |
| Placebo | Time to First Composite Asthma Exacerbations (CompEX) Event | 45.4 weeks |
p-value: 0.683595% CI: [0.55, 1.47]Regression, Cox
Secondary
Absolute Change From Randomization in Fractional Exhaled Nitric Oxide (FeNO) at Week 50
FeNO is a volatile marker of airway inflammation that decreases with inhaled corticosteroid treatment. The measurements recorded were according to standardized procedures by the American Thoracic Society. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FeNO as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FeNO as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or \>=2 events), and geographic region.
Time frame: Randomization [Week 2] to Week 50
Population: mITT population included all randomized participants who received at least one dose of study treatment. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Absolute Change From Randomization in Fractional Exhaled Nitric Oxide (FeNO) at Week 50 | -1.67 parts per billion (ppb) | Standard Error 2.722 |
| Placebo | Absolute Change From Randomization in Fractional Exhaled Nitric Oxide (FeNO) at Week 50 | -1.52 parts per billion (ppb) | Standard Error 2.791 |
p-value: 0.9693Mixed model for repeated measures (MMRM)
Secondary
Absolute Change From Randomization in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 50
FEV1 is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FEV1 as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FEV1 as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/microliter (uL)), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or \>=2 events), and geographic region.
Time frame: Randomization [Week 2] to Week 50
Population: mITT population included all randomized participants who received at least one dose of study treatment. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Absolute Change From Randomization in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 50 | 0.11 liters | Standard Error 0.034 |
| Placebo | Absolute Change From Randomization in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 50 | 0.03 liters | Standard Error 0.034 |
p-value: 0.125Mixed model for repeated measures (MMRM)
Secondary
Area Under Concentration-Time Curve for the First Dosing Interval (AUClast) of MTPS9579A
Time frame: Randomization [Week 2] to Week 6
Population: PK-evaluable population includes all participants who had at least one evaluable PK sample
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Area Under Concentration-Time Curve for the First Dosing Interval (AUClast) of MTPS9579A | 5263.14 day*ug/mL | Geometric Coefficient of Variation 83.6 |
Secondary
Maximum Serum Concentration (Cmax) for the First Dosing Interval of MTPS9579A
Time frame: 2-hour post-dose on Week 2
Population: PK-evaluable population includes all participants who had at least one evaluable PK sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Maximum Serum Concentration (Cmax) for the First Dosing Interval of MTPS9579A | 419 ug/mL | Geometric Coefficient of Variation 51.4 |
Secondary
Maximum Time to Serum Concentration (Tmax) of MTPS9579A
Time frame: Pre-dose and 2-hour post-dose on Week 2
Population: PK-evaluable population includes all participants who had at least one evaluable PK sample.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Maximum Time to Serum Concentration (Tmax) of MTPS9579A | 0.12 day | Standard Deviation 3.41 |
Secondary
Percentage of Participants With Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.
Time frame: Up to approximately Week 58
Population: The safety analysis population included all randomized participants who received at least one dose of study drug during the 48-week double-blind treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MTPS9579A, 1800 mg | Percentage of Participants With Adverse Events | 79.7 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events | 86.2 percentage of participants |
Secondary
Percentage of Participants With Anti-Drug Antibodies (ADA) to MTPS9579A
Treatment Emergent ADA is (a) negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, OR (b) positive ADA result at baseline and one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result.
Time frame: Pre-dose Week 54
Population: The immunogenicity analysis population included all participants with at least one ADA assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MTPS9579A, 1800 mg | Percentage of Participants With Anti-Drug Antibodies (ADA) to MTPS9579A | 5.9 percentage of participants |
| Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) to MTPS9579A | 0 percentage of participants |
Secondary
Rate of Asthma Exacerbations
The number of asthma exacerbations per year was reported for this outcome measure. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Poisson regression was used for the analysis.
Time frame: Randomization [Week 2] to Week 50
Population: mITT population included all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MTPS9579A, 1800 mg | Rate of Asthma Exacerbations | 0.4689 Asthma exacerbations per patient-year |
| Placebo | Rate of Asthma Exacerbations | 0.4267 Asthma exacerbations per patient-year |
p-value: 0.764895% CI: [0.5925, 2.0381]Poisson regression
Secondary
Relative Percent Change From Randomization in FeNO at Week 50
FeNO is a volatile marker of airway inflammation that decreases with inhaled corticosteroid treatment. The measurements recorded were according to standardized procedures by the American Thoracic Society. Relative change (%) in FeNO = (absolute change in FeNO / baseline FeNO) x 100. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the absolute change pre-bronchodilator FeNO as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FeNO as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or \>=2 events), and geographic region.
Time frame: Randomization [Week 2] to Week 50
Population: mITT population included all randomized participants who received at least one dose of study treatment. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Relative Percent Change From Randomization in FeNO at Week 50 | 26.02 percent change | Standard Error 10.223 |
| Placebo | Relative Percent Change From Randomization in FeNO at Week 50 | 26.29 percent change | Standard Error 10.482 |
p-value: 0.9855Mixed model for repeated measures (MMRM)
Secondary
Relative Percent Change From Randomization in Pre-Bronchodilator FEV1 at Week 50
FEV1 was the volume of air exhaled in the first second of a forced exhalation as measured by spirometer. Measurements were performed before use of bronchodilator. Estimates are based on a mixed model for repeated measures (MMRM) analysis with an unstructured covariance matrix. The model used the relative change pre-bronchodilator FEV1 as the response variable and included terms for treatment arm, study visit, treatment arm by study visit interaction, baseline FEV1 as well as its interaction with study visit, in addition to the stratification factors: blood eosinophil level at visit 1 (\<150, \>=150 to \<=300, \>300 cells/uL), number of asthma exacerbations requiring the use of systemic corticosteroids within the 12 months prior to the study entry (1 or \>=2 events), and geographic region. Relative change (%) in FEV1 = (absolute change in FEV1 / baseline FEV1) x 100.
Time frame: Randomization [Week 2] to Week 50
Population: mITT population included all randomized participants who received at least one dose of study treatment. Overall number of participants analyzed are the number of participants available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Relative Percent Change From Randomization in Pre-Bronchodilator FEV1 at Week 50 | 6.44 percent change | Standard Error 1.894 |
| Placebo | Relative Percent Change From Randomization in Pre-Bronchodilator FEV1 at Week 50 | 3.15 percent change | Standard Error 1.921 |
p-value: 0.2249Mixed model for repeated measures (MMRM)
Secondary
Steady State Cmax of MTPS9579A
Time frame: 2-hour post-dose on Week 14
Population: PK-evaluable population includes all participants who had at least one evaluable PK sample
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Steady State Cmax of MTPS9579A | 735 ug/mL | Geometric Coefficient of Variation 31 |
Secondary
Steady State Ctrough of MTPS9579A
Time frame: Pre-dose on Week 14
Population: PK-evaluable population includes all participants who had at least one evaluable PK sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Steady State Ctrough of MTPS9579A | 226 ug/mL | Geometric Coefficient of Variation 45.4 |
Secondary
Time to First Asthma Exacerbation
The time from randomization to first asthma exacerbation was measured. Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that resulted in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Cox regression was used for the analysis.
Time frame: Randomization [Week 2] to Week 50
Population: mITT population included all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MTPS9579A, 1800 mg | Time to First Asthma Exacerbation | NA weeks |
| Placebo | Time to First Asthma Exacerbation | NA weeks |
p-value: 0.524895% CI: [0.43, 1.54]Regression, Cox
Secondary
Trough Serum Concentration (Ctrough) Accumulation Ratio of MTPS9579A
The accumulation ratio is calculated by taking the individual ratio of the Ctrough at Week 14 to the Ctrough at Week 6.
Time frame: Predose on Weeks 6 and 14
Population: PK-evaluable population includes all participants who had at least one evaluable PK sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MTPS9579A, 1800 mg | Trough Serum Concentration (Ctrough) Accumulation Ratio of MTPS9579A | 1.93 ratio | Geometric Coefficient of Variation 28.3 |