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)

Asthma Clinical Trial

— 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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05202262
• Other study ID #: D5982C00006
• Secondary ID: 2021-002026-24
• Status: Recruiting
• Phase: Phase 3
• Start date: January 12, 2022
• Est. completion date: December 2, 2024

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 630
• Est. completion date: December 2, 2024
• Est. primary completion date: December 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• BFF MDI 320/9.6 µg
Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 320/9.6 µg
• BFF MDI 160/9.6 µg
Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 µg
• BD MDI 320 µg
Budesonide MDI (BD MDI), 320 µg
• Open-label Symbicort TBH 320/9 µg
Open-label Symbicort Turbuhaler 320/9 µg

Locations

Country	Name	City	State
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Barrie	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Kamloops	British Columbia
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Stouffville	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois-Rivières	Quebec
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Winnipeg	Manitoba
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Landsberg
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Magdeburg
Germany	Research Site	München-Pasing
Germany	Research Site	Rüdersdorf
Germany	Research Site	Schleswig
Germany	Research Site	Wiesbaden
Germany	Research Site	Witten
Italy	Research Site	Brescia
Italy	Research Site	Mantova
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Rome
Italy	Research Site	Tradate
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fuchu-shi
Japan	Research Site	Fukui-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Habikino-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Kagoshima City
Japan	Research Site	Katsushika-ku
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kodaira-shi
Japan	Research Site	Kokubunji-shi
Japan	Research Site	Kusatsu-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Maebashi-shi
Japan	Research Site	Mizunami-shi
Japan	Research Site	Obihiro-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Setagaya-ku
Japan	Research Site	Shibuya-ku
Japan	Research Site	Tanabe-shi
Japan	Research Site	Toon-shi
Japan	Research Site	Toshima-ku
Japan	Research Site	Toshima-ku
Japan	Research Site	Toshima-ku
Japan	Research Site	Toshima-ku
Japan	Research Site	Utsunomiya-shi
Japan	Research Site	Yokohama
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Malaysia	Research Site	Alor Setar
Malaysia	Research Site	George Town
Malaysia	Research Site	Kajang
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Sarawak Miri
Malaysia	Research Site	Seremban
Spain	Research Site	A Coruña
Spain	Research Site	Alcorcón
Spain	Research Site	Alzira
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Bilbao
Spain	Research Site	Burgos
Spain	Research Site	Granada
Spain	Research Site	Granada
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Oviedo
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Vigo
United States	Research Site	Amarillo	Texas
United States	Research Site	Andrews	Texas
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Bakersfield	California
United States	Research Site	Bakersfield	California
United States	Research Site	Beaumont	Texas
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Boerne	Texas
United States	Research Site	Chandler	Arizona
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cheney	Washington
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbia	Missouri
United States	Research Site	Columbus	Ohio
United States	Research Site	Cutler Bay	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	DeLand	Florida
United States	Research Site	Denver	Colorado
United States	Research Site	Edmond	Oklahoma
United States	Research Site	El Paso	Texas
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Forney	Texas
United States	Research Site	Fresno	California
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Henderson	Nevada
United States	Research Site	Hialeah	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntington Beach	California
United States	Research Site	Kalispell	Montana
United States	Research Site	Knoxville	Tennessee
United States	Research Site	La Palma	California
United States	Research Site	Lexington	Kentucky
United States	Research Site	Lincoln	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Marrero	Louisiana
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Missoula	Montana
United States	Research Site	Monroe	North Carolina
United States	Research Site	New Windsor	New York
United States	Research Site	Newport Beach	California
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	North Las Vegas	Nevada
United States	Research Site	Northridge	California
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Palm Springs	California
United States	Research Site	Peoria	Illinois
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Portsmouth	New Hampshire
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Red Oak	Texas
United States	Research Site	Sacramento	California
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Diego	California
United States	Research Site	San Jose	California
United States	Research Site	Saraland	Alabama
United States	Research Site	Skillman	New Jersey
United States	Research Site	Tampa	Florida
United States	Research Site	Tucson	Arizona
United States	Research Site	Victoria	Texas
United States	Research Site	Waco	Texas
United States	Research Site	Wheat Ridge	Colorado
United States	Research Site	White Marsh	Maryland
United States	Research Site	Williamsburg	Virginia
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Canada,  Germany,  Italy,  Japan,  Malaysia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	at week 24
Secondary	US (Key secondary): Change from baseline in morning pre-dose trough FEV1 at Week 24	US (Key secondary): Change from baseline in morning pre-dose trough FEV1 at Week 24	at week 24
Secondary	Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 24 Weeks	Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 24 Weeks	over 24 weeks
Secondary	Percentage of responders in ACQ-7 (= 0.5 decrease equals response) at Week 24	Percentage of responders in ACQ-7 (= 0.5 decrease equals response) at Week 24	at week 24
Secondary	Percentage of responders in ACQ-5 (= 0.5 decrease equals response) at Week 24	Percentage of responders in ACQ-5 (= 0.5 decrease equals response) at Week 24	at Week 24
Secondary	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	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	at Week 24
Secondary	Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1	Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1	Day 1