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)

NCT05202262 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: D5982C000062024-513568-24-002021-002026-24
• Study Type: interventional
• Target: 645
• Locations: 7 countries
• Sites: 142

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0 to 3 Hours (AUC0-3) at Week 24

  Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24. FEV1 AUC0-3 is calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time to report the result in liters. Treatment policy is implemented to handle all intercurrent events with the exception of initiation of new asthma therapy or administration of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of randomised study intervention, for which the composite strategy is implemented.

  At Week 24

Secondary Outcomes (8)

• Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24

  At 24 Weeks

• Onset of Action on Day 1: Absolute Change in FEV1 at 5 Minutes on Day 1

  On Day 1

• Change From Baseline in the Mean Number of Puffs of Rescue Medication Use (Puffs/Day) Over 24 Weeks

  Over 24 Weeks

• Percentage of Responders in ACQ-7 (≥ 0.5 Decrease Equals Response) at Week 24

  At Week 24

• Percentage of Responders in ACQ-5 (≥ 0.5 Decrease Equals Response) at Week 24

  At Week 24

Study Arms (4)

BFF MDI 320/9.6 μg

EXPERIMENTAL

Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 320/9.6 μg

Drug: BFF MDI 320/9.6 μg

BFF MDI 160/9.6 μg

EXPERIMENTAL

Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg

Drug: BFF MDI 160/9.6 μg

BD MDI 320 μg

EXPERIMENTAL

Budesonide MDI (BD MDI), 320 μg

Drug: BD MDI 320 μg

Open-label Symbicort TBH 320/9 μg

ACTIVE COMPARATOR

Open-Label Comparator Symbicort Turbuhaler 320/9 μg

Drug: Open-label Symbicort TBH 320/9 μg

Interventions

BFF MDI 320/9.6 μg DRUG

Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 320/9.6 μg

Also known as: BFF

BFF MDI 320/9.6 μg

BFF MDI 160/9.6 μg DRUG

Budesonide/ Formoterol Fumarate (BFF) metered-dose inhaler (MDI), 160/9.6 μg

Also known as: BFF

BFF MDI 160/9.6 μg

BD MDI 320 μg DRUG

Budesonide MDI (BD MDI), 320 μg

Also known as: BD

BD MDI 320 μg

Open-label Symbicort TBH 320/9 μg DRUG

Open-label Symbicort Turbuhaler 320/9 μg

Also known as: Symbicort TBH

Open-label Symbicort TBH 320/9 μg

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• ACQ-7 total score ≥ 1.5 at Visits 1 and 4.
• 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).
• 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.
• 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.
• Asthma stability during run-in based on Investigator discretion using the symptom worsening assessment.
• Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
• Demonstrate acceptable MDI administration technique.
• 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.

You may not qualify if:

• 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).
• 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.
• Hospitalization for asthma within 8 weeks of Visit 1.
• 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.
• Known history of drug or alcohol abuse within 12 months of Visit 1.
• Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1.
• 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.
• Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001).
• Use of a nebulizer or a home nebulizer for receiving asthma medications.
• 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.
• 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).
• Participants with known hypersensitivity to beta2-agonists, corticosteroids, or any component of the MDI.
• 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.
• 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).
• Planned hospitalization during the study.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (142)

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Chandler, Arizona, 85224, United States

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Tucson, Arizona, 85745, United States

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Bakersfield, California, 93301, United States

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Fresno, California, 93720, United States

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Huntington Beach, California, 92647, United States

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La Palma, California, 90623, United States

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Lincoln, California, 95648, United States

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Los Angeles, California, 90017, United States

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Los Angeles, California, 90025, United States

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Los Angeles, California, 90048, United States

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Newport Beach, California, 92663, United States

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Northridge, California, 91324, United States

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Sacramento, California, 95823, United States

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San Diego, California, 92120, United States

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San Diego, California, 92123, United States

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San Jose, California, 95117, United States

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Denver, Colorado, 80230, United States

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Wheat Ridge, Colorado, 80033, United States

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Cutler Bay, Florida, 33189, United States

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DeLand, Florida, 32720, United States

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Miami, Florida, 33155, United States

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Miami, Florida, 33173, United States

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Miami, Florida, 33175, United States

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Miami, Florida, 33180, United States

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Tampa, Florida, 33607, United States

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Atlanta, Georgia, 30361, United States

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Peoria, Illinois, 61636, United States

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Lexington, Kentucky, 40509, United States

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White Marsh, Maryland, 21162, United States

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North Dartmouth, Massachusetts, 02747, United States

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Farmington Hills, Michigan, 48336, United States

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Columbia, Missouri, 65203, United States

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Saint Charles, Missouri, 63301, United States

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St Louis, Missouri, 63141, United States

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Kalispell, Montana, 59901, United States

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Missoula, Montana, 59808, United States

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Bellevue, Nebraska, 68123, United States

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Omaha, Nebraska, 68114, United States

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Henderson, Nevada, 89052, United States

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North Las Vegas, Nevada, 89030, United States

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Portsmouth, New Hampshire, 03801, United States

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Skillman, New Jersey, 08558, United States

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Gastonia, North Carolina, 28054, United States

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Monroe, North Carolina, 28112, United States

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Raleigh, North Carolina, 27607, United States

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Cincinnati, Ohio, 45236, United States

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Columbus, Ohio, 43215, United States

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Edmond, Oklahoma, 73034, United States

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Oklahoma City, Oklahoma, 73120, United States

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Portland, Oregon, 97202, United States

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Pittsburgh, Pennsylvania, 15236, United States

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Knoxville, Tennessee, 37909, United States

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Austin, Texas, 78759, United States

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Beaumont, Texas, 77701, United States

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Boerne, Texas, 78006, United States

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Dallas, Texas, 75231, United States

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El Paso, Texas, 79912, United States

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Forney, Texas, 75126, United States

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Houston, Texas, 77093, United States

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Red Oak, Texas, 75154, United States

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San Antonio, Texas, 78229, United States

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San Antonio, Texas, 78258, United States

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Victoria, Texas, 77901, United States

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Waco, Texas, 76712, United States

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Williamsburg, Virginia, 23188, United States

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Milwaukee, Wisconsin, 53228, United States

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Calgary, Alberta, T3B 0M3, Canada

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Calgary, Alberta, T3E 7M8, Canada

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Edmonton, Alberta, T5A 4L8, Canada

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Kamloops, British Columbia, V2C 5T1, Canada

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Winnipeg, Manitoba, R3L 1Z5, Canada

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Moncton, New Brunswick, E1G 1A7, Canada

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Ajax, Ontario, L1S 2J5, Canada

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Burlington, Ontario, L7N 3V2, Canada

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Stouffville, Ontario, L4A 1H2, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Windsor, Ontario, N8X 2G1, Canada

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Windsor, Ontario, N8X-5A6, Canada

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Montreal, Quebec, H2V 2K1, Canada

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Québec, Quebec, G1G 3Y8, Canada

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Québec, Quebec, G1V 4W2, Canada

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Québec, Quebec, G2J 0C4, Canada

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Berlin, 10119, Germany

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Berlin, 10787, Germany

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Berlin, 10961, Germany

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Berlin, 12157, Germany

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Berlin, 13156, Germany

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Frankfurt am Main, 60596, Germany

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Landsberg, 86899, Germany

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Leipzig, 04157, Germany

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Leipzig, 04207, Germany

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Leipzig, 04299, Germany

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Magdeburg, 39120, Germany

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München-Pasing, 81241, Germany

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Schleswig, 24837, Germany

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Wiesbaden, 65189, Germany

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Witten, 58452, Germany

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Brescia, 25123, Italy

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Mantova, 46100, Italy

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Naples, 80131, Italy

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Roma, 00133, Italy

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Roma, 00168, Italy

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Rome, 00165, Italy

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Tradate, 21049, Italy

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Chūōku, 103-0022, Japan

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Chūōku, 103-0027, Japan

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Chūōku, 103-0028, Japan

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Chūōku, 104-0031, Japan

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Fukui-shi, 910-8526, Japan

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Fukuoka, 819-8555, Japan

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Himeji-shi, 672-8064, Japan

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Kagoshima, 890-0053, Japan

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Kishiwada-shi, 596-8501, Japan

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Kodaira-shi, 187-0024, Japan

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Kokubunji-shi, 185-0014, Japan

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Kusatsu-shi, 525-8585, Japan

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Kyoto, 601-8213, Japan

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Kyoto, 612-8555, Japan

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Mizunami-shi, 509-6134, Japan

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Obihiro-shi, 080-0013, Japan

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Osaka, 531-0073, Japan

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Sapporo, 062-0931, Japan

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Setagaya-ku, 158-0097, Japan

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Shibuya-ku, 150-0013, Japan

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Toon-shi, 791-0281, Japan

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Toshima-ku, 170-0002, Japan

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Toshima-ku, 170-0003, Japan

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Toshima-ku, 171-0014, Japan

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Utsunomiya, 329-1193, Japan

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Yokohama, 223-0059, Japan

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Yokohama, 232-0024, Japan

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Yokohama, 232-0064, Japan

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Badalona, 08916, Spain

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Barcelona, 08017, Spain

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Bilbao, 48002, Spain

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Granada, 18004, Spain

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Granada, 18014, Spain

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Madrid, 28041, Spain

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Santiago de Compostela, 15702, Spain

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Vigo, 36201, Spain

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Related Links

• CSR Synopsis

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Open Label for Symbicort TBH
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: January 21, 2022
• Study Start: January 12, 2022
• Primary Completion: February 26, 2025
• Study Completion: February 26, 2025
• Last Updated: January 28, 2026
• Results First Posted: January 28, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

ES (8); VN (2); JP (28); US (66); DE (15); CA (16); IT (7)