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.
Brief Title
A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller
Categories
Completion Date
Completion Date Type
Actual
Conditions
Asthma
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT04092582
Org Class
Industry
Org Full Name
Genentech, Inc.
Org Study Id
GB41149
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase IIa, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller
Primary Outcomes
Outcome Description
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.
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.
Outcome Measure
Time to First Composite Asthma Exacerbations (CompEX) Event
Outcome Time Frame
Randomization [Week 2] to end of treatment (EOT) [Week 50]
Secondary Ids
Secondary Id
2019-000795-41
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Randomization [Week 2] to Week 50
Outcome Measure
Rate of Asthma Exacerbations
Outcome Description
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.
Outcome Time Frame
Randomization [Week 2] to Week 50
Outcome Measure
Time to First Asthma Exacerbation
Outcome Description
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.
Outcome Time Frame
Randomization [Week 2] to Week 50
Outcome Measure
Absolute Change From Randomization in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 50
Outcome Description
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.
Outcome Time Frame
Randomization [Week 2] to Week 50
Outcome Measure
Relative Percent Change From Randomization in Pre-Bronchodilator FEV1 at Week 50
Outcome Description
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.
Outcome Time Frame
Randomization [Week 2] to Week 50
Outcome Measure
Absolute Change From Randomization in Fractional Exhaled Nitric Oxide (FeNO) at Week 50
Outcome Description
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.
Outcome Time Frame
Randomization [Week 2] to Week 50
Outcome Measure
Relative Percent Change From Randomization in FeNO at Week 50
Outcome Description
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.
Outcome Time Frame
Up to approximately Week 58
Outcome Measure
Percentage of Participants With Adverse Events
Outcome Time Frame
Randomization [Week 2] to Week 6
Outcome Measure
Area Under Concentration-Time Curve for the First Dosing Interval (AUClast) of MTPS9579A
Outcome Time Frame
2-hour post-dose on Week 2
Outcome Measure
Maximum Serum Concentration (Cmax) for the First Dosing Interval of MTPS9579A
Outcome Time Frame
2-hour post-dose on Week 14
Outcome Measure
Steady State Cmax of MTPS9579A
Outcome Time Frame
Pre-dose and 2-hour post-dose on Week 2
Outcome Measure
Maximum Time to Serum Concentration (Tmax) of MTPS9579A
Outcome Description
The accumulation ratio is calculated by taking the individual ratio of the Ctrough at Week 14 to the Ctrough at Week 6.
Outcome Time Frame
Predose on Weeks 6 and 14
Outcome Measure
Trough Serum Concentration (Ctrough) Accumulation Ratio of MTPS9579A
Outcome Time Frame
Pre-dose on Week 14
Outcome Measure
Steady State Ctrough of MTPS9579A
Outcome Description
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.
Outcome Time Frame
Pre-dose Week 54
Outcome Measure
Percentage of Participants With Anti-Drug Antibodies (ADA) to MTPS9579A
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Golda Hudes
Investigator Email
ghudes@montefiore.org
Investigator Phone
646-229-9509