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Submitted by: Trishia Torero 2021-02-05 06:37:34 Last Updated by: Trishia Torero 2021-03-30 10:15:35


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 (KALOS)

PHRR210205-003330

D5982C00007

2020-CT0581

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

This is a Phase III randomized, double-blind, double dummy, parallel group, multicenter variable length efficacy and safety study comparing two doses of BGF MDI (320/28.8/9.6 µg and 320/14.4/9.6 µg) to BDD MDI 320/9.6 µg (an ICS/LABA currently under development) and Symbicort pMDI 320/9 µg in adult and adolescent participants who have asthma which remains inadequately controlled (ACQ-7 total score ≥1.5) despite treatment with a medium or high dose of ICS/LABA. Adult participants (but not adolescents) must also have a documented history of at least one severe asthma exacerbation in the 12 months prior to Visit 1. All doses represent the sum of two actuations. All study interventions will be administered twice daily (BID) for a minimum of 24 weeks and a maximum of 52 weeks.

Regime Classification Priority
2017 - 2022 Global competitiveness and innovation in health Drug Discovery and Development
Start Date Duration in Months Target Completion Date Actual Completion Date
2021-04-01 26 2023-06-01 0000-00-00

Pending

Awaiting approval of CSP version 2 and release of import license

Institution Classification Region LTO #
AstraZeneca Pharmaceuticals (Philippines) Inc. Private Business NCR LTO-3000002234602
Institution Region
AstraZeneca Pharmaceuticals (Philippines) Inc. NCR
Name E-Mail Institution and Institution Address
Ariane Marmeto ariane.marmeto@astrazeneca.com 16th Floor, Inoza Tower, 40th Street, Bonifacio Global City, Taguig, 1634, Philippines
Name E-Mail Institution and Institution Address
Ariane Marmeto ariane.marmeto@astrazeneca.com 16th Floor, Inoza Tower, 40th Street, Bonifacio Global City, Taguig, 1634, Philippines
Name Expertise Affiliation
Albert Albay, Jr. MD Pulmonology Manila Doctors Hospital
Dexter D. Feliciano, MD Pulmonology Baguio General Hospital and Medical Center
Eloisa S. De Guia, MD Pulmonology Veterans Memorial Medical Center
Iris Ruth Batalla, MD Pulmonology Davao Doctors Hospital
Jose Felipe Hernandez, MD Pulmonology Mary Mediatrix Medical Center
Lalaine Llamido Mortera, MD Pulmonology Manila Central University - Filemon D. Tanchoco Medical Foundation
Leonora Fernandez, MD Pulmonology University of the Philippines - Philippine General Hospital
Liza Llanes Garcia Pulmonology The Medical City
Manuel Peter Paul C. Jorge II, MD Pulmonary University of the Philippines - Philippine General Hospital
Marie Grace Dawn T. Isidro, MD Pulmonology West Visayas State University Medical Center
Mary Jane T. Sandagon, MD Pulmonary Las Piñas Doctor's Hospital, Inc.
Ronnie Z. Samoro, MD Pulmonology Healthlink Medical-Surgical-Dental Clinics & Diagnostics Center
Sullian S. Naval, MD Pulmonology Lung Center of the Philippines
Project Location Institutional Ethics Review Board
Manila Doctors Hospital Manila Doctors Hospital Institutional Review Board
Baguio General Hospital and Medical Center Baguio General Hospital and Medical Center Ethics Review Committee
Veterans Memorial Medical Center Veterans Memorial Medical Center Ethics Review Committee
Davao Doctors Hospital Davao Doctors Hospital Ethics Review Committee
Mary Mediatrix Medical Center Mary Mediatrix Medical Center Research Ethics Review Committee
Manila Central University - Filemon D. Tanchoco Medical Foundation Manila Central University - Filemon D. Tanchoco Medical Foundation Institutional Review Board
University of the Philippines - Philippine General Hospital N/A
The Medical City The Medical City - Institutional Review Board
University of the Philippines - Philippine General Hospital N/A
West Visayas State University Medical Center N/A
Las Piñas Doctor's Hospital, Inc. Las Piñas Doctor's Hospital, Inc.
Healthlink Medical-Surgical-Dental Clinics & Diagnostics Center N/A
Lung Center of the Philippines Lung Center of the Philippines Ethics Review Committee

Adult and Adolescent Participants with Inadequately Controlled Asthma

  • Change from Baseline in FEV1 AUC0-3 (US Primary Endpoint)
  • Change from Baseline in Morning Pre-dose Trough FEV(EU and Japan Primary Endpoint)

  • Percentage of responders in ACQ-7 (≥0.5 decrease equals response) and ACQ (≥0.5 decrease equals response)
  • Percentage of Responders in the Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12) (≥0.5 increase equals response)
  • Percentage of Responders in the St. George's Respiratory Questionnaire (SGRQ) (≥ 4.0 unit decrease equals response)
  • Onset of Action on Day 1
  • Rate of Severe Asthma Exacerbation

Pending

  • Argentina
  • Australia
  • Belgium
  • Bulgaria
  • Canada
  • Chile
  • Denmark
  • France
  • Hungary
  • India
  • Italy
  • Japan
  • Netherlands
  • Peru
  • Philippines
  • Poland
  • Romania
  • South Korea
  • Spain
  • Taiwan
  • Thailand
  • United States
  • Vietnam

Clinical Trial

D5982C00007

Unspecified

0000-00-00

0000-00-00

140

Unspecified

Unspecified

01 Apr 2021

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

Age

  • Participant must be at least 12 to 80 years of age inclusive, at the time of signing the ICF.
  • Note: For participants from 12 to

Type of Participant and Disease Characteristics

  • Participants who have a documented history of physician-diagnosed asthma ≥1 year prior to Visit 1, according to GINA guidelines [GINA 2020]. Healthcare records for 1 year prior to Visit 1 must be provided for adolescent participants (12 to
  • Participants who have been regularly using a stable daily ICS/LABA regimen (including a stable ICS dose), with the ICS doses allowed in Table 7, for at least 4 weeks prior to Visit 1.
  • Have a documented history of at least one asthma exacerbation requiring use of systemic corticosteroids (oral or IV) for at least 3 days AND an associated physician visit, hospitalization, or ER visit due to asthma (within 3 days of the corticosteroid use) in the 12 months prior to Visit 1.
    • Note: This criterion does not apply for participants 12 to
  • ACQ-7 total score ≥1.5 at Visits 1, 3, and 5 (pre-randomization).
  • A pre-bronchodilator FEV1 <80% predicted normal value at Visits 1, 2, 3, 4, and 5 (pre-randomization) for participants ≥18 years of age OR a pre-bronchodilator FEV1 <90% predicted normal value at Visits 1, 2, 3, 4, and 5 (pre-randomization) for participants 12 to
  • Note: Participants who have not withheld asthma medications prior to Visit 1 and failed spirometry testing at Visit 1 should return to the clinic to repeat spirometry testing within two days. If repeat spirometry failed, then participants must be screen-failed.
  • Documented reversibility to albuterol, which is defined as a post-albuterol increase in FEV1 of ≥12% and ≥200 mL for participants ≥18 years of age OR a post-albuterol increase of FEV1 of ≥12% for participants 12 to
  • Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
  • Demonstrate acceptable MDI/pMDI administration technique.
    • Note: Historical use of a spacer device within the 4 weeks prior to and/or during the Screening and Randomized Treatment Periods is not permitted.

Weight

  • Body mass index 2.

Sex

  • Male and/or female

Reproduction

  • Negative urine pregnancy test for female participants ≤60 years of age.
  • Women of childbearing potential must agree to acceptable contraceptive measures, as judged by the Investigator.

Informed Consent

  • Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Criteria to be Confirmed at Visit 5

  • Received no asthma medication other than run-in BFF MDI BID and albuterol as needed during screening, except for allowed medications defined in Table 8 and systemic corticosteroid or ICS for the treatment of an asthma exacerbation (see Section 5.2 regarding Screening extension).
  • 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).
  • 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.
  • Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.

Conditional Inclusion criterion

Note: Inclusion criterion #19 will replace Inclusion criterion #6 if the pre-bronchodilator FEV1 >55% of predicted normal stratum is closed during the study as described in Section 4.1.

  • A pre-bronchodilator FEV1 <55% predicted normal value at Visits 1, 2, 3, 4, and 5 (pre-randomization).

 

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

  • 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).
  • Completed treatment for respiratory infection or asthma exacerbation with systemic corticosteroids within 4 weeks of Visit 1.
  • Participants where, in the opinion of the Investigator, treatment with biological therapy for asthma would be appropriate.
  • Hospitalization for asthma within 2 months 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 (e.g., 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 if the disease/condition exacerbated during the study.
  • Known history of drug or alcohol abuse within 12 months of Visit 1.
  • 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.
    • Note: All medications approved for control of intraocular pressures are allowed, including topical ophthalmic non-selective beta-blockers.
  • Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant.
    • Note: Participants with trans-urethral resection of prostate or full resection of the prostate within 6 months prior to Visit 1 are excluded from the study.
  • Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1.
    • Note: Squamous cell and basal cell carcinomas of the skin are not exclusionary.

Prior/Concomitant Therapy

  • Oral and IV corticosteroid use (any dose) within 4 weeks of Visit 1. 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.
  • Depot corticosteroid use for any reason within 12 months of Visit 1.
  • Use of LAMA as maintenance treatment, either alone or as part of an inhaled combination therapy, within 12 months prior to Visit 1.
  • Use of oral beta2-agonist within 3 months of Visit 1.
  • Any marketed (e.g., omalizumab, mepolizumab, benralizumab, reslizumab) or investigational biologic within 3 months or 5 half-lives of Visit 1, whichever is longer and must not be used during study duration.
  • Regular use of a nebulizer or a home nebulizer for receiving asthma medications.
    • Note: Acute use of a nebulizer for an asthma exacerbation during acute healthcare attendance is allowed as long as there is no occurrence within 4 weeks of Visit 1.
  • Use of any immunomodulators or immunosuppressive medication within 3 months or 5 half-lives, whichever is longer, and must not be used during study duration.
    • Note: Topical administration of immunosuppressive medication may be allowed at the discretion of the Investigator.
  • Unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods.
  • Participants with personalized treatment action plans at home who are not willing to contact the site prior to the start of prednisolone (or equivalent) for the treatment of an asthma exacerbation.
  • Using any herbal products by inhalation or nebulizer within 4 weeks of Visit 1 and does not agree to stop during the study duration.

Prior/Concurrent Clinical Study Experience

  • Participation in another clinical study with an Investigational Product administered in the last 30 days or 5 half-lives, whichever is longer. Any other Investigational Product that is not identified in this protocol is prohibited for use during study duration.
  • Participants with a known hypersensitivity to beta2-agonists, corticosteroids, anticholinergics, or any component of the MDI or pMDI.

Diagnostic assessments

  • Calculated creatinine clearance ≤30 mL/minute using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for participants 18 to 80 years of age and on repeat prior to Visit 5 OR using the Schwartz formula for participants 12 to
  • Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, 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.
    • Note: Participants with ECG QTcF interval (corrected for heart rate using Fridericia’s formula [QTcF]) ≥500 msec will be excluded. Participants with high degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses whom are not treated with pacemaker will also be excluded.

Other Exclusions

  • Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking
  • Planned hospitalization during the study.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  • Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.
  • Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
  • Previous or current randomization in any budesonide and formoterol fumarate studies (PT009), budesonide, glycopyrronium, and formoterol fumarate studies (PT010), or glycopyrronium studies (PT001).
  • 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.

Interventional

Budesonide, Glycopyrronium, and Formoterol Fumarate Metered Dose Inhaler (MDI)

Study interventions are masked in a double dummy fashion, whereby participants randomized to BGF MDI or BFF MDI are given placebo pMDI to match Symbicort pMDI and participants randomized to Symbicort pMDI are given placebo MDI to match BGF/BFF MDI.

Placebo MDI and pMDI devices will be provided for training purposes. Run-in BFF MDI will be provided during the Screening Period.

Date Amendment Classification Reason
2021-03-26 Amendments related to the protocol Informed consent

Randomized

Double Blind

Unspecified

Parallel

The primary objective of this study is to assess the effect of BGF MDI relative to BFF MDI and Symbicort pMDI on lung function in participants with inadequately controlled asthma.

Phase III

Utilization Utilization Info
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