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

• ClinicalTrials.gov Identifier: NCT04609904
• Recruitment Status: Recruiting
• First Posted: October 30, 2020
• Last Update Posted: May 8, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: October 26, 2020
• First Posted Date: October 30, 2020
• Last Update Posted Date: May 8, 2024
• Actual Study Start Date: March 1, 2021
• Estimated Primary Completion Date: March 21, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (submitted: July 11, 2023)

• 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. Additional analysis will be conducted using pooled data from studies D5982C00007 and D5982C00008
• 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
• 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(s) +12) (≥0.5 increase equals response) at Week 24. Additional analysis will be conducted using pooled data from studies D5982C00007 and D5982C00008
• 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
• Rate of severe asthma exacerbations for participants with percent predicted FEV1 ≤ 55% at baseline. [ Time Frame: Up to 52 Weeks ]
  Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Rate of severe asthma exacerbations for participants with percent predicted FEV1 ≤ 55% at baseline.
• Rate of severe asthma exacerbations for participants with ≥ 1 severe exacerbation in the 12 months prior to Visit 1. [ Time Frame: Up to 52 Weeks ]
  Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Rate of severe asthma exacerbations for participants with ≥ 1 severe exacerbation in the 12 months prior to Visit 1.

Original Secondary Outcome Measures (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
• Rate of severe asthma exacerbations over the Treatment Period [ Time Frame: Up to 52 Weeks ]
  Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Rate of severe asthma exacerbations over the Treatment Period
• Time to first severe asthma exacerbation (assessed over the Treatment Period only) [ Time Frame: Up to 52 Weeks ]
  Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Time to first severe asthma exacerbation (assessed over the Treatment Period only)
• Rate of moderate/severe asthma exacerbations over the Treatment Period [ Time Frame: Up to 52 Weeks ]
  Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Rate of moderate/severe asthma exacerbations over the Treatment Period
• Time to first moderate/severe asthma exacerbation (assessed over the Treatment Period only) [ Time Frame: Up to 52 Weeks ]
  Secondary end point(s) of Pooled Studies D5982C00007 and D5982C00008: Time to first moderate/severe asthma exacerbation (assessed over the Treatment Period only)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess PT010 in Adult and Adolescent Participants With Inadequately Controlled Asthma (LOGOS)
• 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
• 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 2200 participants will be randomized globally.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Asthma

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 12, 2022): 2200
• Original Estimated Enrollment (submitted: October 26, 2020): 2800
• Estimated Study Completion Date: March 21, 2025
• Estimated Primary Completion Date: March 21, 2025 (Final data collection date for primary outcome measure)

Eligibility 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: 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Austria, Brazil, China, Colombia, Costa Rica, Czechia, Germany, Greece, Israel, Mexico, Portugal, Puerto Rico, Russian Federation, Saudi Arabia, Slovakia, South Africa, Sweden, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT04609904
• Other Study ID Numbers: D5982C00008; 2023-505786-88 ( Registry Identifier: CTIS ); 2020-001521-31 ( 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

• 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
• Supporting Materials: 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

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Robert Wise, MD; Johns Hopkins University

• PRS Account: AstraZeneca
• Verification Date: April 2024