A RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, PARALLEL GROUP, MULTICENTER 24 TO 52 WEEK VARIABLE LENGTH STUDY TO ASSESS THE EFFICACY AND SAFETY OF BUDESONIDE, GLYCOPYRRONIUM, AND FORMOTEROL FUMARATE METERED DOSE INHALER (MDI) RELATIVE TO BUDESONIDE AND FORMOTEROL FUMARATE MDI AND SYMBICORT®PRESSURIZED MDI IN ADULT AND ADOLESCENT PARTICIPANTS WITH INADEQUATELY CONTROLLED ASTHMA (KALOS)
- Conditions
- -J459 Asthma, unspecifiedAsthma, unspecifiedJ459
- Registration Number
- PER-096-20
- Lead Sponsor
- AstraZeneca AB,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
5.1Inclusion Criteria
1-Participant must be at least 12 to 80 years of age inclusive, at the time of signing the ICF.
Note: For participants from 12 to <18 years of age, their parents or legal guardians must give their signed written informed consent, as appropriate, and participants will sign an assent form.
2-Participants who have a documented history of physician-diagnosed asthma ≥1 year prior to Visit 1, according to GINA guidelines [GINA 2020]. Healthcare records for 1 year prior to Visit 1 must be provided for adolescent participants (12 to <18 years of age) to ensure consistent evaluation and follow-up of treatment in those participants.
3-Participants who have been regularly using a stable daily ICS/LABA regimen (including a stable ICS dose), with the ICS doses allowed in Table 7, for at least 4 weeks prior to Visit 1.Have a documented history of at least one asthma exacerbation requiring use of systemic corticosteroids (oral or IV) for at least 3 days AND an associated physician visit, hospitalization, or ER visit due to asthma (within 3 days of the corticosteroid use) in the 12 months prior to Visit 1.
Note: This criterion does not apply for participants 12 to <18 years of age.
5-ACQ-7 total score ≥1.5 at Visits 1, 3, and 5 (pre-randomization).
6-A pre-bronchodilator FEV1 <80% predicted normal value at Visits 1, 2, 3, 4, and 5 (pre-randomization) for participants ≥18 years of age OR a pre-bronchodilator FEV1 <90% predicted normal value at Visits 1, 2, 3, 4, and 5 (pre-randomization) for participants 12 to <18 years of age.
Note: Participants who have not withheld asthma medications prior to Visit 1 and failed spirometry testing at Visit 1 should return to the clinic to repeat spirometry testing within two days. If repeat spirometry failed, then participants must be screen-failed.
7Documented reversibility to albuterol, which is defined as a post-albuterol increase in FEV1 of ≥12% and ≥200 mL for participants ≥18 years of age OR a post-albuterol increase of FEV1 of ≥12% for participants 12 to <18 years of age at Visit 2, or at Visit 3 if repeat testing necessary.
8-Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
9-Demonstrate acceptable MDI/pMDI administration technique.
Note: Historical use of a spacer device within the 4 weeks prior to and/or during the Screening and Randomized Treatment Periods is not permitted.
10-Body mass index <40 kg/m2.
11-Male and/or female
12-Negative urine pregnancy test for female participants ≤60 years of age.
13-Women of childbearing potential must agree to acceptable contraceptive measures, as judged by the Investigator.
14-Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
15-Received no asthma medication other than run-in BFF MDI BID and albuterol as needed during screening, except for allowed medications defined in Table 8 and systemic corticosteroid or ICS for the treatment of an asthma exacerbation (see Section 5.5.2 regarding Screening extension).
16-eDiary 14-day compliance ≥70% during screening (defined as completing the daily eDiary for any 10 mornings, and any 10 evenings, and answering Yes” to taking 2 puffs of run-in BFF MDI for any 10 mornings and 10 evenings i
5.2Exclusion Criteria
1Life-threatening asthma defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s).
2Completed treatment for respiratory infection or asthma exacerbation with systemic corticosteroids within 4 weeks of Visit 1.
3Participants where, in the opinion of the Investigator, treatment with biological therapy for asthma would be appropriate.
4Hospitalization for asthma within 2 months of Visit 1.
5Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary (e.g., active tuberculosis, bronchiectasis, pulmonary eosinophilic syndromes, and COPD). Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or that could affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
6Known history of drug or alcohol abuse within 12 months of Visit 1.
7Narrow angle glaucoma not adequately treated and/or change in vision that may be relevant, in the opinion of the Investigator, within 3 months of Visit 1.
Note: All medications approved for control of intraocular pressures are allowed, including topical ophthalmic non-selective beta-blockers.
8Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant.
Note: Participants with trans-urethral resection of prostate or full resection of the prostate within 6 months prior to Visit 1 are excluded from the study.
9Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1.
Note: Squamous cell and basal cell carcinomas of the skin are not exclusionary.
10Oral and IV corticosteroid use (any dose) within 4 weeks of Visit 1. Use of systemic corticosteroids for any other reason except for the acute treatment of severe asthma exacerbation is prohibited for the duration of the study.
11Depot corticosteroid use for any reason within 12 months of Visit 1.
12Use of LAMA as maintenance treatment, either alone or as part of an inhaled combination therapy, within 12 months prior to Visit 1.
13Use of oral beta2-agonist within 3 months of Visit 1.
14Any marketed (e.g., omalizumab, mepolizumab, benralizumab, reslizumab) or investigational biologic within 3 months or 5 half-lives of Visit 1, whichever is longer and must not be used during study duration.
15Regular use of a nebulizer or a home nebulizer for receiving asthma medications.
Note: Acute use of a nebulizer for an asthma exacerbation during acute healthcare attendance is allowed as long as there is no occurrence within 4 weeks of Visit 1.
16Use of any immunomodulators or immunosuppressive medication within 3 months or 5 half-lives, whichever is longer, and must not be used during study duration.
Note: Topical administration of immunosuppressive medication may be allowed at the discretion of the Investigator.
17Unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods.
18Participants with personalized treatment action plans at home who are not willing to contact the site prior to the sta
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Difference in mean change from baseline<br>Measure:To assess the effect of BGF MDI relative to BFF MDI or Symbicort pMDI on lung function in participants with inadequately controlled asthma.<br>Timepoints:US: Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24<br>Europe (EU): Change from baseline in morning pre-dose trough FEV1 over 24 Weeks<br>Japan: Change from baseline in morning pre-dose trough FEV1 over 12 to 24 Weeks<br>
- Secondary Outcome Measures
Name Time Method