A PHASE IIB, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER, DOSE-RANGING STUDY TO ASSESS THE EFFICACY AND SAFETY OF MSTT1041A IN PATIENTS WITH UNCONTROLLED SEVERE ASTHMA
- Conditions
- -J45Nonallergic asthmaJ45J451
- Registration Number
- PER-048-16
- Lead Sponsor
- A
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 24
Inclusion Criteria
4.1.1.1 Inclusion Criteria for Enrollment in the Run-In Period
Patients must meet the following criteria to be eligible for enrollment in the run-in period:
• Signed Informed Consent Form
• Age 18−75 years at time of signing Informed Consent Form
• Able to comply with the study protocol, in the investigator’s judgment
• Body mass index (BMI) of 18−35 kg/m2 and weight ≥ 40 kg at screening
• Documented physician-diagnosed asthma for at least 12 months prior to screening
• On ICS therapy at a total daily dose ≥ 500 μg of fluticasone propionate or equivalent plus at least one additional allowed controller medication, 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
-Patients may receive one or more of the following additional controller medications: LABA, LTM, LAMA, or long-acting theophylline preparation.
• Morning pre-bronchodilator FEV1 of 40%−80% of predicted at the screening and run-in (Week 0) visits
• Post-bronchodilator reversibility of FEV1 (liters) of ≥ 12% and ≥ 200 mL at screening
-Patients are allowed up to three attempts to meet reversibility criteria, within the screening period (see Section 4.5.2 for details).
- Specific guidelines for performing and interpreting bronchodilator reversibility testing, including medication-withholding strategies and appropriate dosing of short-acting bronchodilators, will be provided to investigators.
• Uncontrolled asthma during the screening period, defined as an ACQ-5 score ≥ 1.5 and at least one of the following symptoms of asthma that is not controlled according to EPR3 (2007) and GINA (2015) guidelines:
Nighttime awakening ≥ 1 time/week
-Use of short-acting rescue therapy > 2 days/week
- Documented history of at least one asthma exacerbation within 12 months prior to screening while on daily ICS maintenance therapy (same dose as at screening), defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that result in one or both of the following:
-Hospitalization or emergency department or urgent care visit requiring administration of asthma treatment, such as bronchodilators and/or systemic corticosteroids, in addition to baseline controller medications
-Treatment with systemic corticosteroids for ≥ 3 days or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of ≥ 3 days
• Demonstrated compliance with required use of the eDiary, defined as documenting asthma controller medication use and answering questions related to asthma symptoms, nighttime awakenings due to asthma, and use of short-acting rescue therapy on 5 of 7 days during each of 2 consecutive weeks during the screening period (see Section 4.5.5.2 and Section 4.5.5.3 for details)
• Demonstrated compliance with required PEFR measurements, defined as measuring PEFR on 5 of 7 days during each of 2 consecutive weeks during the screening period (see Section 4.5.5.1 for details)
• Demonstrated adherence with usual asthma controller medication regimen, defined as patients responding affirmatively that they have taken their asthma controller medications on 5 of 7 days during each of 2 consecutive
+ Exclusion Criteria for Enrollment in the Run-In Period:
Patients who meet any of the following criteria will be excluded from enrollment in the
run-in period:
• Diagnosis of vocal cord dysfunction, reactive airways dysfunction syndrome, hyperventilation associated with panic attacks, or other mimics of asthma
• Diagnosis of occupational asthma, aspirin-sensitive asthma, asthma−chronic obstructive pulmonary disease (COPD) overlap syndrome, or bronchiolitis, as determined by the investigator
• Pregnant or lactating, or intending to become pregnant during the study or within 20 weeks after the last dose of MSTT1041A
-Women of childbearing potential must have a negative serum pregnancy test result during the screening period.
• History of smoking (tobacco or marijuana) or vaping within 6 months prior to screening, significant smoking history (defined as ≥ 10 pack-years), or unwilling to abstain from smoking from the time of consent through the completion of the study
-A pack-year is defined as the average number of packs of cigarettes per day times the number of years of smoking
• History or evidence of substance abuse that would pose a risk to patient safety, interfere with the conduct of the study, have an impact on the study results, or affect the patient´s ability to participate in the study, in the opinion of the investigator
• History or evidence of a medical condition or any clinically significant disorder, condition, or disease (e.g., psychiatric or other mental health disorder, renal failure, coronary artery disease, cardiomyopathy, heart failure, hypertension, liver disease, diabetes, anemia) that is uncontrolled despite treatment or that is likely, in the opinion of the investigator, to require a change in therapy, pose a risk to patient safety, interfere with the conduct of the study, have an impact on the study results, or affect the patient´s ability to participate in the study
-Patients with well-controlled comorbid disease on a stable treatment regimen for 4 weeks prior to screening are eligible for the study.
• Myocardial infarction, unstable angina pectoris, or stroke within 12 months prior to screening
• Any finding on the screening ECG that requires further cardiovascular evaluation (such as evidence of prior myocardial infarction, cardiomyopathy, or substantial left or right ventricular hypertrophy), in the opinion of the investigator
• QT interval corrected using Fridericia’s formula (QTcF) > 440 ms demonstrated by at least two ECGs > 30 minutes apart
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease, clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
• Current treatment with medications that are well known to prolong the QT interval • Evidence of active liver disease, including jaundice or AST, ALT, total bilirubin, or alkaline phosphatase > 2 × upper limit of normal (ULN)
• Acute infection requiring either surgical intervention (e.g., drainage) or medical therapy (e.g., antibiotics) within 4 weeks prior to screening
• Helminthic parasitic infection diagnosed within 6 months prior to screening that has not been treated or has not responded to standard-o
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method