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Study to Assess PT010 in Adult and Adolescent Participants With Inadequately Controlled Asthma (KALOS) (KALOS)

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ClinicalTrials.gov Identifier: NCT04609878
Recruitment Status : Recruiting
First Posted : October 30, 2020
Last Update Posted : July 16, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 26, 2020
First Posted Date  ICMJE October 30, 2020
Last Update Posted Date July 16, 2021
Actual Study Start Date  ICMJE December 15, 2020
Estimated Primary Completion Date July 25, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 26, 2020)
  • Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24 [ Time Frame: 24 Weeks ]
    Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24
  • Rate of severe asthma exacerbations [ Time Frame: Up to 52 weeks ]
    Primary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Rate of severe asthma exacerbations
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2020)
  • Change from baseline in morning pre-dose trough FEV1 at Week 24 [ Time Frame: 24 Weeks ]
    Change from baseline in morning pre-dose trough FEV1 at Week 24
  • Percentage of responders in Asthma Control Questionnaire (ACQ)-7 (≥0.5 decrease equals response) at Week 24 [ Time Frame: 24 weeks ]
    Percentage of responders in ACQ-7 (≥0.5 decrease equals response) at Week 24
  • Percentage of responders in ACQ-5 (≥0.5 decrease equals response) at Week 24 [ Time Frame: 24 Weeks ]
    Percentage of responders in ACQ-5 (≥0.5 decrease equals response) at Week 24
  • Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ +12) (≥0.5 increase equals response) at Week 24 [ Time Frame: 24 weeks ]
    Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ +12) (≥0.5 increase equals response) at Week 24
  • Percentage of responders in the St. George's Respiratory Questionnaire (SGRQ) (≥4.0 unit decrease equals response) at Week 24 [ Time Frame: 24 Weeks ]
    Percentage of responders in the St. George's Respiratory Questionnaire (SGRQ) (≥4.0 unit decrease equals response) at Week 24
  • Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1 [ Time Frame: Day 1 ]
    Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1
  • Time to first severe asthma exacerbation [ Time Frame: Up to 52 Weeks ]
    Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Time to first severe asthma exacerbation
  • Rate of moderate/severe asthma exacerbations [ Time Frame: Up to 52 Weeks ]
    Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Rate of moderate/severe asthma exacerbations
  • Time to first moderate/severe asthma exacerbation [ Time Frame: Up to 52 weeks ]
    Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Time to first moderate/severe asthma exacerbation
Original Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2020)
  • Change from baseline in morning pre-dose trough FEV1 at Week 24 [ Time Frame: 24 Weeks ]
    Change from baseline in morning pre-dose trough FEV1 at Week 24
  • Percentage of responders in ACQ-7 (≥0.5 decrease equals response) at Week 24 [ Time Frame: 24 weeks ]
    Percentage of responders in ACQ-7 (≥0.5 decrease equals response) at Week 24
  • Percentage of responders in ACQ-5 (≥0.5 decrease equals response) at Week 24 [ Time Frame: 24 Weeks ]
    Percentage of responders in ACQ-5 (≥0.5 decrease equals response) at Week 24
  • Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ +12) (≥0.5 increase equals response) at Week 24 [ Time Frame: 24 weeks ]
    Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ +12) (≥0.5 increase equals response) at Week 24
  • Percentage of responders in the St. George's Respiratory Questionnaire (SGRQ) (≥4.0 unit decrease equals response) at Week 24 [ Time Frame: 24 Weeks ]
    Percentage of responders in the St. George's Respiratory Questionnaire (SGRQ) (≥4.0 unit decrease equals response) at Week 24
  • Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1 [ Time Frame: Day 1 ]
    Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1
  • Time to first severe asthma exacerbation [ Time Frame: Up to 52 Weeks ]
    Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Time to first severe asthma exacerbation
  • Rate of moderate/severe asthma exacerbations [ Time Frame: Up to 52 Weeks ]
    Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Rate of moderate/severe asthma exacerbations
  • Time to first moderate/severe asthma exacerbation [ Time Frame: Up to 52 weeks ]
    Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Time to first moderate/severe asthma exacerbation
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Assess PT010 in Adult and Adolescent Participants With Inadequately Controlled Asthma (KALOS)
Official Title  ICMJE A Randomized, Double-Blind, Double Dummy, Parallel Group, Multicenter Variable Length Study to Assess the Efficacy and Safety of PT010 Relative to PT009 and Symbicort® in Adult and Adolescent Participants With Inadequately Controlled Asthma
Brief Summary This is a variable length study to evaluate the efficacy and safety of budesonide/glycopyrronium/formoterol inhaler in adults and adolescents with severe asthma inadequately controlled with standard of care.
Detailed Description This is 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. Approximately 2800 participants will be randomized globally.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: BGF MDI 320/28.8/9.6 μg
    Budesonide, glycopyrronium, and formoterol fumarate metered dose inhaler
    Other Name: BGF
  • Drug: BGF MDI 320/14.4/9.6 μg
    Budesonide, glycopyrronium, and formoterol fumarate metered dose inhaler
    Other Name: BGF
  • Drug: BFF MDI 320/9.6 μg
    Budesonide and formoterol fumarate metered dose inhaler
    Other Name: BFF
  • Drug: BFF pMDI 320/9 μg
    Budesonide/formoterol fumarate pressurized metered dose inhaler
    Other Name: Symbicort®
Study Arms  ICMJE
  • Experimental: Budesonide, glycopyrronium, and formoterol fumarate (BGF) MDI 320/28.8/9.6 μg
    BGF MDI 320/28.8/9.6 μg Budesonide, glycopyrronium, and formoterol fumarate (PT010) Metered Dose Inhaler (MDI)
    Intervention: Drug: BGF MDI 320/28.8/9.6 μg
  • Experimental: BGF MDI 320/14.4/9.6 μg
    BGF MDI 320/14.4/9.6 μg Budesonide, glycopyrronium, and formoterol fumarate (PT010) Metered Dose Inhaler (MDI)
    Intervention: Drug: BGF MDI 320/14.4/9.6 μg
  • Active Comparator: Budesonide and formoterol fumarate (BFF) MDI 320/9.6 μg
    BFF MDI 320/9.6 μg (Experimental/Comparator) Budesonide and formoterol fumarate (PT009) Metered Dose Inhaler (MDI)
    Intervention: Drug: BFF MDI 320/9.6 μg
  • Active Comparator: Symbicort®
    Budesonide/ formoterol fumarate pressurized metered dose inhaler (pMDI) 320/9 μg
    Intervention: Drug: BFF pMDI 320/9 μg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 26, 2020)
2800
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 25, 2023
Estimated Primary Completion Date July 25, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Documented history of physician-diagnosed asthma > and/or = 1 year prior to V1.
  2. Documented history of at least one asthma exacerbation requiring use of systemic corticosteroids (SCS) (oral or IV) for at least 3 days and an associated physician visit, hospitalization, or emergency room visit due to asthma (within 3 days of the corticosteroid use) in the 12 months prior to V1 (Not applicable to adolescents).
  3. 12 to 80 years of age, male and female, BMI <40 kg/m2.
  4. FEV1 post-albuterol at V2 or V3 (if repeat needed).

    • Participants > and/or = 18 years of age: Increase > and/or = 12% and > and/or = 200 mL.
    • Participants 12 to <18 years of age: Increase > and/or = 12%.
  5. FEV1 % predicted normal at V1, 2, 3, 4, and 5 (pre-randomization).

    • Participants > and/or = 18 years of age: < 80%
    • Participants 12 to <18 years of age: < 90%
  6. ACQ-7 total score > and/or = 1.5 at V1, 3, 5.
  7. Regularly using a stable daily Inhaled Corticosteroid/Long-Acting β2-Agonist (ICS/LABA) regimen (including a stable ICS dose), with medium to high ICS doses for at least 4 weeks prior to V1.
  8. Electronic Diary (eDiary) compliance > and/or = 70% during screening (defined as completed daily eDiary entry and answering "yes" for taking 2 puffs of run-in BFF MDI for any 10 mornings, and any 10 evenings in the last 14 days prior to randomization).
  9. No respiratory infection within 4 weeks of randomization, or asthma exacerbation treated with systemic corticosteroid and/or additional ICS treatment within 4 weeks of randomization.
  10. Demonstrate acceptable MDI/pMDI administration technique.

Exclusion Criteria:

1. Completed treatment for respiratory infection or asthma exacerbation with systemic corticosteroids within 4 weeks of V1.

2a. Participants where, in the opinion of the Investigator, treatment with biological therapy for asthma would be appropriate.

2b. Any marketed or investigational biologics within 3 months or 5 half-lives of V1, whichever is longer and must not be used during study duration.

3. Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months prior to V1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).

4. Current evidence of Chronic Obstructive Pulmonary Disease (COPD). 5a. Oral and IV corticosteroid use (any dose) within 4 weeks of V1. 5b. 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.

5c. Depot corticosteroid use for any reason within 12 months of V1. 6. Use of Long-Acting Muscarinic Antagonist (LAMA) as maintenance treatment, either alone or as part of an inhaled combination therapy, within 12 months prior to V1.

7. Use of oral b2-agonist within 3 months of V1. 8. Use of any immunomodulators or immunosuppressive medication within 3 months or 5 half-lives, whichever is longer, and must not be used during the study duration.

9. 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.

10. 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).

11. Hospitalization for asthma within 2 months of Visit 1. 12. Known history of drug or alcohol abuse within 12 months of Visit 1. 13. Regular use of a nebulizer or a home nebulizer for receiving asthma medications.

14. Using any herbal products by inhalation or nebulizer within 4 weeks of Visit 1 and does not agree to stop during the study duration.

15. Participation in another clinical study with an Investigational Product. 16. Participants with a known hypersensitivity to beta2-agonists, corticosteroids, anticholinergics, or any component of the MDI or pMDI.

17. Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.

18. For women only - currently pregnant (confirmed with positive pregnancy test), breast-feeding, or planned pregnancy during the study or not using acceptable contraception measures, as judged by the Investigator.

Please refer to the study protocol for the complete inclusion and exclusion criteria list.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Bulgaria,   Canada,   Chile,   Denmark,   Hungary,   India,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Peru,   Philippines,   Poland,   Puerto Rico,   Romania,   Spain,   Taiwan,   Thailand,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04609878
Other Study ID Numbers  ICMJE D5982C00007
2020-001520-34 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrew Menzies-Gow, MD Royal Brompton Hospital, United Kingdom
PRS Account AstraZeneca
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP