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Study to assess the safety and efficacy of BGF (Budesonide, Glycopyrronium and Formoterol Fumerate) relative to BFF (Budesonide Formoterol Fumerate) and Symbicort with inadequate controlled Asthma.

Phase 3
Conditions
Health Condition 1: J459- Other and unspecified asthma
Registration Number
CTRI/2021/05/033456
Lead Sponsor
AstraZeneca AB
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Open to Recruitment
Sex
Not specified
Target Recruitment
0
Inclusion Criteria

Age

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.

Type of Participant and Disease Characteristics

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.

Participants who have been regularly using a stable daily ICS/LABA regimen (including

a stable ICS dose), with the ICS doses allowed in Table 8, for at least 4 weeks prior to

Visit 1

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.

Documented reversibility to Albuterol, which is defined as a post-Albuterol increase in FEV1of >=12% and >=200 mL for participants >=18 years of age OR a post-Albuterol increase of FEV1of >=12% for participants 12 to <18 years of age at Visit 2, or at Visit 3 if repeat testing necessary.

Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.

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.

Weight

Body mass index <40 kg/m2.

Sex

Male and/or female; females must be not of childbearing potential or using a form of highly effective birth control as defined below

Female participants: Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply:

i). Women <50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range.

ii). Women >=50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.

Female participants of childbearing potential must use a highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistent

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

i. Life-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).

ii. Completed treatment for respiratory infection or asthma exacerbation with systemic corticosteroids in the 4 weeks prior to Visit 1.

iii. Participants where, in the opinion of the Investigator, treatment with biological therapy for asthma would be appropriate.

iv. Hospitalization for asthma within 2 months of Visit1.

v. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, haematological, 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.

vi. Known history of drug or alcohol abuse within 12 months of Visit 1.

vii. Narrow 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.

viii. Symptomatic 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.

ix. Unresectable 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.

Prior/Concomitant Therapy

x. Oral 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.

xi. Depot corticosteroid use for any reason within 12 months of Visit 1.

xii. Use of LAMA as maintenance treatment, either alone or as part of an inhaled combination therapy, within 12 months prior to Visit 1.

xiii. Use of oral beta2-agonist within 3 months of Visit 1.

xiv. Any 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.

xv. Regular 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.

xvi. Use of any immunomodulators or immunosuppressive medication within 3 months or 5half-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.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To assess the effect of BGF MDI relative to BFF MDI or Symbicort pMDI on lung function in participants with inadequately controlled asthmaTimepoint: Change from baseline in morning pre-dose trough FEV1over 24 Weeks
Secondary Outcome Measures
NameTimeMethod
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