A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MTPS9579A in Patients With Asthma Requiring Inhaled Corticosteroids and a Second Controller
- Conditions
- Asthma
- Interventions
- Drug: MTPS9579ADrug: Placebo
- Registration Number
- NCT04092582
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 135
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MTPS9579A MTPS9579A - Placebo Placebo -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
Steady State Ctrough of MTPS9579A Pre-dose on Week 14 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 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.
Trial Locations
- Locations (27)
Florida Ctr-Allergy & Asthma
🇺🇸Miami, Florida, United States
ALL-MED Specjalistyczna Opieka Medyczna
🇵🇱Wroclaw, Poland
Kern Research
🇺🇸Bakersfield, California, United States
Centrum Medyczne ALL-MED
🇵🇱Krakow, Poland
Fundacion Cidea
🇦🇷Buenos Aires, Argentina
Florida Pulmonary Research Institute, LLC
🇺🇸Winter Park, Florida, United States
Allergy & Asthma Medical Group of the Bay Area
🇺🇸Walnut Creek, California, United States
CARE - Centro de Alergia y Enfermedades Respiratorias
🇦🇷Caba, Argentina
Pneumologicum
🇩🇪Hannover, Germany
Centro Respiratorio Quilmes
🇦🇷Quilmes, Argentina
Clinica Ricardo Palma; THORAX
🇵🇪Lima, Peru
IKF Pneumologie
🇩🇪Frankfurt am Main, Germany
Toledo Inst of Clin Research
🇺🇸Toledo, Ohio, United States
OK Clinical Research
🇺🇸Edmond, Oklahoma, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Spartanburg Medical Research
🇺🇸Spartanburg, South Carolina, United States
Centro Médico Dra. Cristina de Salvo
🇦🇷Buenos Aires, Argentina
Research Center for Medical Studies RCMS
🇩🇪Berlin, Germany
BAG Prof Dr G Hoheisel Dr A Bonitz
🇩🇪Leipzig, Germany
SMO.MD GmbH, Zentrum für klinische Studien
🇩🇪Magdeburg, Germany
Clinica Providencia (Inverconsult Sociedad Anonima)
🇵🇪Lima, Peru
Malopolskie Centrum Alergologii
🇵🇱Krakow, Poland
SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
🇵🇱Lodz, Poland
Ostrowieckie Centrum Medyczne Spolka Cywilna Anna Olec-Cudzik; Krzysztof Cudzik
🇵🇱Ostrowiec Swietokrzysk, Poland
Centrum Alergologii Teresa Hofman
🇵🇱Poznan, Poland
PULMAG Grzegorz Gasior Marzena Kociolek Spolka Cywilna
🇵🇱Sosnowiec, Poland
Centrum Medycyny Oddechowej Robert M. Mróz
🇵🇱Bialystok, Poland