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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04609878
Recruitment Status : Recruiting
First Posted : October 30, 2020
Last Update Posted : July 1, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Asthma Drug: BGF MDI 320/28.8/9.6 μg Drug: BGF MDI 320/14.4/9.6 μg Drug: BFF MDI 320/9.6 μg Drug: BFF pMDI 320/9 μg Phase 3

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 2200 participants will be randomized globally.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 15, 2020
Estimated Primary Completion Date : January 16, 2024
Estimated Study Completion Date : January 16, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
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)
Drug: BGF MDI 320/28.8/9.6 μg
Budesonide, glycopyrronium, and formoterol fumarate metered dose inhaler
Other Name: BGF

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)
Drug: BGF MDI 320/14.4/9.6 μg
Budesonide, glycopyrronium, and formoterol fumarate metered dose inhaler
Other Name: BGF

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)
Drug: BFF MDI 320/9.6 μg
Budesonide and formoterol fumarate metered dose inhaler
Other Name: BFF

Active Comparator: Symbicort®
Budesonide/ formoterol fumarate pressurized metered dose inhaler (pMDI) 320/9 μg
Drug: BFF pMDI 320/9 μg
Budesonide/formoterol fumarate pressurized metered dose inhaler
Other Name: Symbicort®




Primary Outcome Measures :
  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 [ 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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. Additional analysis will be conducted using pooled data from studies D5982C00007 and D5982C00008

  3. 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. Additional analysis will be conducted using pooled data from studies D5982C00007 and D5982C00008

  4. 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. Additional analysis will be conducted using pooled data from studies D5982C00007 and D5982C00008

  5. 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

  6. 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

  7. 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


  8. 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


  9. 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




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Documented history of physician-diagnosed asthma > and/or = 1 year prior to V1.
  3. Regularly using a stable daily ICS/LABA regimen (including a stable ICS dose) with medium-to-high ICS doses for at least 4 weeks prior to V1.
  4. ACQ-7 total score ≥1.5 at Visits 1, 3, and 5 (pre-randomization).
  5. FEV1 % (assessed as an average of the 60 and 30 minute pre-dose assessments) 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. 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 =12% either in the 12 months prior to Visit 1 or at Visit 2, or at Visit 3.
    • Note: Reversibility testing is still required at Visit 2 and/or Visit 3, even if the patient has documented historical reversibility reported in the 12 months prior to Visit 1.
  7. Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
  8. Demonstrate acceptable MDI/pMDI administration technique.
  9. Received no asthma medication other than run-in BFF MDI BID and albuterol as needed during screening (except for allowed medications as defined in Table 9 and systemic corticosteroid or ICS for the treatment of an asthma exacerbation).
  10. eDiary 14-day compliance ≥70% during screening (defined as completing the daily eDiary for any 10 mornings and any 10 evenings and answering "Yes" to taking 2 puffs of run-in BFF MDI for any 10 mornings and 10 evenings in the last 14 days prior to randomization).
  11. No respiratory infection in the 4 weeks prior to randomization, or asthma exacerbation treated with systemic corticosteroid and/or additional ICS treatment in the 4 weeks prior to randomization.

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), either alone or as part of an inhaled combination therapy, in the 12 weeks 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 highly sensitive 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04609878


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Andrew Menzies-Gow, MD Royal Brompton Hospital, United Kingdom
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04609878    
Other Study ID Numbers: D5982C00007
2020-001520-34 ( EudraCT Number )
First Posted: October 30, 2020    Key Record Dates
Last Update Posted: July 1, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting Materials: Study Protocol
Statistical Analysis Plan (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
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Budesonide, Formoterol Fumarate Drug Combination
Anti-Asthmatic Agents
Respiratory System Agents