Clinical trial NCT05202262: A 24-Week Efficacy and Safety Study to Assess Budesonide and Formoterol Fumarate Metered Dose Inhaler in Adult and Adolescent Participants With Inadequately Controlled Asthma (VATHOS)
Official title: A Randomized, Double-Blind, Parallel Group, Multicenter 24 Week Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler Relative to Budesonide Metered Dose Inhaler and Open-Label Symbicort® Turbuhaler® in Participants With Inadequately Controlled Asthma (VATHOS).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-01-21
Enrollment: 644
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 24 week study to evaluate the efficacy and safety of budesonide and formoterol fumarate metered dose inhaler in adults and adolescents with inadequately controlled asthma.

Detailed description: This is a Phase III randomized, double-blind, active comparison, parallel group, multicenter study comparing BFF MDI 320/9.6 μg to BD MDI 320 µg and open-label Symbicort TBH 320/9 μg in adult and adolescent participants who have asthma which remains inadequately controlled (ACQ-7 total score ≥ 1.5) despite treatment with medium dose ICS or ICS/LABA. Budesonide and Formoterol Fumarate MDI 160/9.6 μg is included in this study to evaluate dose response by comparing to BFF MDI 320/9.6 μg. All doses represent the sum of 2 actuations. All study interventions will be administered BID for 24 weeks.

This study will be conducted at approximately 125 sites worldwide and will randomize approximately 630 adult and adolescent participants.

Eligibility criteria: Inclusion Criteria:

1. 12 to 80 years of age, male and female, BMI \<40 kg/m2; females must be not of childbearing potential or using a form of highly effective birth control.
2. Participants who have a documented history of physician-diagnosed asthma ≥ 6 months prior to Visit 1, according to GINA guidelines \[GINA 2020\]. Healthcare records for one 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 or an ICS/LABA regimen (including a stable ICS dose), with the ICS doses, for at least 8 weeks prior to Visit 1.
4. ACQ-7 total score ≥ 1.5 at Visits 1 and 4.
5. Pre-bronchodilator/pre-dose FEV1 \<90% predicted normal value at Visits 1, 2 and 3, and a pre-dose FEV1 of 50% to 90% at Visit 4 (pre-randomization).
6. Reversibility to albuterol, defined as a post-albuterol increase in FEV1 of ≥ 12% and ≥ 200 mL for participants ≥ 18 years of age OR a post-albuterol increase in FEV1 of ≥ 12% for participants 12 to \< 18 years of age, either in the 12 months prior to Visit 1 or at Visit 2 or Visit 3.
7. A pre-bronchodilator/pre-dose FEV1 at Visits 2, 3, and 4 that have not changed 20% or more (increase or decrease) from the pre-bronchodilator/pre-dose FEV1 recorded at the previous visit.
8. Asthma stability during run-in based on Investigator discretion using the symptom worsening assessment.
9. Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
10. Demonstrate acceptable MDI administration technique.
11. eDiary compliance ≥ 70% during screening, defined as completing the daily eDiary and answering "Yes" to taking 2 puffs of run-in BD MDI for any 10 mornings and 10 evenings in the last 14 days prior to randomization.

Exclusion Criteria:

1. Life-threatening asthma as defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s).
2. Any respiratory infection or asthma exacerbation treated with systemic corticosteroids and/or additional ICS treatment in the 8 weeks prior to Visit 1 and throughout the Screening Period.
3. Hospitalization for asthma within 8 weeks of Visit 1.
4. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary (eg, 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.
5. Known history of drug or alcohol abuse within 12 months of Visit 1.
6. Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1.
7. Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer. Any other study intervention that is not identified in this protocol is prohibited for use during study duration.
8. Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001).
9. Use of a nebulizer or a home nebulizer for receiving asthma medications.
10. Do not meet the stable dosing period prior to Visit 1 or unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods.
11. Receipt of COVID-19 vaccine (regardless of vaccine delivery platform, eg, vector, lipid nanoparticle) \< 7 days prior to Visit 1 (from last vaccination or booster dose).
12. Participants with known hypersensitivity to beta2-agonists, corticosteroids, or any component of the MDI.
13. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or ECG, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study.
14. Current smokers, former smokers with \> 10 pack-years history, or former smokers who stopped smoking \< 6 months prior to Visit 1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).
15. Planned hospitalization during the study.
16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
17. Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.
18. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.
19. For women only - currently pregnant (confirmed with positive highly sensitive urine pregnancy test), breast-feeding, or planned pregnancy during the study or not using acceptable contraception measures, as judged by the Investigator.

Primary outcomes:
measure: United States (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
timeFrame: at week 24
Secondary outcomes:
measure: US (Key secondary): Change from baseline in morning pre-dose trough FEV1 at Week 24
timeFrame: at week 24
measure: Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 24 Weeks
timeFrame: over 24 weeks
measure: Percentage of responders in ACQ-7 (≥ 0.5 decrease equals response) at Week 24
timeFrame: at week 24
measure: Percentage of responders in ACQ-5 (≥ 0.5 decrease equals response) at Week 24
timeFrame: at Week 24
measure: Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) (≥ 0.5 increase equals response) at Week 24
timeFrame: at Week 24
measure: Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1
timeFrame: Day 1
Other outcomes:
Locations:
city: Chandler
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state: Arizona
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Badalona
country: Spain
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country: Spain
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country: Spain
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city: Granada
country: Spain
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city: Granada
country: Spain
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city: Madrid
country: Spain
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city: Santiago de Compostela
country: Spain
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city: Vigo
country: Spain
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city: Hanoi
country: Vietnam
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city: Ho Chi Minh
country: Vietnam
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Study officials:
References: