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

AstraZeneca2,187 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

2,187

Conditions

Asthma

Interventions

BGF MDI 320/28.8/9.6 μgDRUG

Budesonide, glycopyrronium, and formoterol fumarate metered dose inhaler

BGF MDI 320/14.4/9.6 μgDRUG

Budesonide, glycopyrronium, and formoterol fumarate metered dose inhaler

BFF MDI 320/9.6 μgDRUG

Budesonide and formoterol fumarate metered dose inhaler

Eligibility

Sex: ALLMin age: 12 YearsMax age: 80 Years

Medical Language ↔ Plain English

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: Even if there is documented history of reversibility, all participants must be assessed for reversibility at Visit 2 (and Visit 3, if reversibility is not demonstrated at Visit 2) to provide reversibility baseline data for characterization. 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 halflives 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 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 3 months of V1. 6\. Use of LAMA, either alone or as part of an inhaled combination therapy, in the 12 weeks prior to Visit 1. 7\. Use of oral beta2-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 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 the protocol is prohibited for use during study duration. 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

Locations (317)

Outcomes

Primary Outcomes

Change From Baseline in FEV1 AUC0-3 (L) 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. Treatment policy was implemented to handle all intercurrent events (ICEs) with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24

Pooled (LOGOS/KALOS): Rate of Severe Asthma Exacerbations

Rate of severe asthma exacerbations was assessed in a pre-specified pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). An asthma exacerbation was severe if it resulted in at least 1 of the following: systemic corticosteroids for 3 days, an ER/urgent care visit requiring systemic corticosteroids, a hospitalization, or death related to asthma. Consecutive exacerbations with start/stop days ≤7 days apart were considered the same event. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Up to 52 Weeks

Secondary Outcomes

Change From Baseline in Morning Pre-dose Trough FEV1 (L) at Week 24

Change from baseline in morning pre-dose trough FEV1 at Week 24. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24

Onset of Action on Day 1: Absolute Change in FEV1 (L) at 5 Minutes on Day 1

Onset of action on Day 1: Absolute change in FEV1 (L) at 5 minutes on Day 1. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Data from ClinicalTrials.gov

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Budesonide/formoterol fumarate pressurized metered dose inhaler

Research Site

Chandler, Arizona, United States

Research Site

Tempe, Arizona, United States

Research Site

Tucson, Arizona, United States

Research Site

Hot Springs, Arkansas, United States

Research Site

Bakersfield, California, United States

Research Site

Carlsbad, California, United States

Research Site

Huntington Beach, California, United States

Research Site

Lancaster, California, United States

Research Site

Long Beach, California, United States

Research Site

Mission Viejo, California, United States

...and 307 more locations

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

Percentage of responders in Asthma Control Questionnaire (ACQ)-7 (≥0.5 decrease equals response) at Week 24. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24

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. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24

Percentage of Responders in 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. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24

Percentage of Responders in SGRQ (≥4.0 Decrease Equals Response) at Week 24

Percentage of responders in the St. George's Respiratory Questionnaire (SGRQ) (≥4.0 decrease equals response) at Week 24. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24

Pooled (LOGOS/KALOS): Rate of Severe Asthma Exacerbations for Participants With Percent Predicted FEV1 ≤55% at Baseline

Rate of severe asthma exacerbations for participants with percent predicted FEV1 ≤55% at baseline was assessed in a pre-speciﬁed pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). An asthma exacerbation was severe if it resulted in at least 1 of the following: systemic corticosteroids for 3 days, an ER/urgent care visit requiring systemic corticosteroids, a hospitalization, or death related to asthma. Consecutive exacerbations with start/stop days ≤7 days apart were considered the same event. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Up to 52 Weeks

Pooled (LOGOS/KALOS): Rate of Severe Asthma Exacerbations for Participants With ≥1 Severe Exacerbation in the 12 Months Prior to Visit 1

Rate of severe asthma exacerbations for participants with ≥1 severe exacerbation in the 12 months prior to Visit 1 was assessed in a pre-speciﬁed pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). An asthma exacerbation was severe if it resulted in at least 1 of the following: systemic corticosteroids for 3 days, an ER/urgent care visit requiring systemic corticosteroids, a hospitalization, or death related to asthma. Consecutive exacerbations with start/stop days ≤7 days apart were considered the same event. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Up to 52 Weeks

Pooled (LOGOS/KALOS): Time to First Severe Asthma Exacerbation

Time to first severe asthma exacerbation was assessed in a pre-specified pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). Time to first severe asthma exacerbation was the time from the first dose of study medication to the time of onset of the first severe asthma exacerbation. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Up to 52 weeks

Pooled (LOGOS/KALOS): Rate of Moderate or Severe Asthma Exacerbations

Rate of moderate/severe exacerbations was assessed in a pre-speciﬁed pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). An exacerbation was severe if it resulted in at least 1 of the following: systemic corticosteroids for 3 days, an ER/urgent care visit requiring systemic corticosteroids, an inpatient hospitalization, or death related to asthma. A moderate exacerbation was a worsening of symptoms that resulted in additional ICS for 3 days. Consecutive exacerbations with start/stop days ≤7 days apart were considered the same event. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Up to 52 Weeks

Pooled (LOGOS/KALOS): Time to First Moderate or Severe Asthma Exacerbation

Time to first moderate/severe asthma exacerbation was assessed in a pre-specified pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). Time to first moderate or severe asthma exacerbation was the time from the first dose of study medication to the time of onset of the first moderate/severe asthma exacerbation. Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Up to 52 weeks

Pooled (LOGOS/KALOS): 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 was assessed in a pre-speciﬁed pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24

Pooled (LOGOS/KALOS): 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 was assessed in a pre-speciﬁed pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24

Pooled (LOGOS/KALOS): Percentage of Responders in AQLQ(s) +12 (≥0.5 Increase Equals Response) at Week 24

Percentage of responders in AQLQ(s) +12 (≥0.5 increase equals response) at Week 24 was assessed in a pre- speciﬁed pooled analysis across replicate studies D5982C00008 and D5982C00007 (NCT04609878). Treatment policy was implemented to handle all ICEs with the exception of initiation of new asthma therapy or use of prohibited medications thought to impact efficacy in conjunction with premature discontinuation of study intervention, for which the composite strategy was implemented.

Time frame: Week 24