Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 in Subjects With Moderate to Very Severe COPD (Ethos)

• ClinicalTrials.gov Identifier: NCT02465567
• Recruitment Status: Completed
• First Posted: June 8, 2015
• Results First Posted: February 2, 2021
• Last Update Posted: February 2, 2021
• Sponsor: Pearl Therapeutics, Inc.
• Information provided by (Responsible Party): Pearl Therapeutics, Inc.

Tracking Information

• First Submitted Date: May 29, 2015
• First Posted Date: June 8, 2015
• Results First Submitted Date: June 26, 2020
• Results First Posted Date: February 2, 2021
• Last Update Posted Date: February 2, 2021
• Actual Study Start Date: June 30, 2015
• Actual Primary Completion Date: July 26, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2021)

Adjusted Rate of Moderate or Severe Exacerbations [ Time Frame: 52-week treatment period ]

Adjusted Rate of Moderate or Severe Exacerbations

Original Primary Outcome Measures (submitted: June 5, 2015)

effects of BGF MDI relative to GFF MDI and BFF MDI on lung function assessed by pulmonary function tests [ Time Frame: (52-week treatment period) ]

(Pulomonary Function Tests will be conducted over 4 hours in a subset of approximately 3,060 subjects (765 subjects per treatment group) at selected visits)

Current Secondary Outcome Measures (submitted: February 1, 2021)

• Time to First Moderate or Severe COPD Exacerbation [ Time Frame: 52 Weeks ]
  Time to first moderate or severe COPD exacerbation (proportion with event reported as median time was not reached, statistical analyses are based upon time to event)
• Change From Baseline in Average Daily Rescue Ventolin HFA Use Over 24 Weeks [ Time Frame: 24 Weeks ]
  Change from baseline in average daily rescue Ventolin HFA use over 24 weeks
• Percentage of Subjects Achieving a MCID of 4 Units or More in SGRQ Total Score [ Time Frame: at Week 24 ]
  Percentage of subjects achieving a minimal clinically important difference (MCID) of 4 units or more in SGRQ (St. George's Respiratory Questionnaire) total score at Week 24
• Time to Death (All Cause) [ Time Frame: 52 Weeks ]
  Subject Deaths (all cause)
• Rate of Severe COPD Exacerbations [ Time Frame: 52 Weeks ]
  Rate of severe COPD exacerbations

Original Secondary Outcome Measures (submitted: June 5, 2015)

• effect of BGF MDI relative to GFF MDI and BFF MDI on symptoms of COPD assessed by EXACT [ Time Frame: (52-week treatment period) ]
  COPD Assessment - Exacerbations of Chronic Pulmonary Disease Tool (EXACT)
• effect of BGF MDI relative to GFF MDI and BFF MDI on quality of life [ Time Frame: (52-week treatment period) ]
  For Quality of Life, European Quality-of-Life-5 Dimension-5 Level Questionnaire
• effect of BGF MDI relative to GFF MDI and BFF MDI on all cause mortality [ Time Frame: (52-week treatment period) ]

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

Descriptive Information

• Brief Title: Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 in Subjects With Moderate to Very Severe COPD (Ethos)
• Official Title: A Randomized, Double-Blind, Multi-Center, Parallel-Group Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 on COPD Exacerbations Over a 52-Week Treatment Period in Subjects With Moderate to Very Severe COPD (Ethos)
• Brief Summary: This is a randomized, double-blind, multi-center, parallel-group study to assess the efficacy and safety of PT010 relative to PT003 and PT009 on COPD exacerbations subjects with moderate to very severe COPD.
• Detailed Description: A randomized, double-blind, multi-center, parallel-group study to assess the efficacy and safety of PT010 relative to PT003 and PT009 on COPD exacerbations over a 52-week treatment period in subjects with moderate to very severe COPD.
• 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: COPD

Intervention

• Drug: BGF MDI 320/14.4/9.6 μg
  Budensonide, Glycopyrronium, and Formoterol Fumarate
  Other Name: BGF
• Drug: GFF MDI 14.4/9.6 μg
  Glycopyrronium, and Formoterol Fumarate
  Other Name: GFF
• Drug: BGF MDI 160/14.4/9.6 μg
  Budensonide, Glycopyrronium, and Formoterol Fumarate
  Other Name: BGF
• Drug: BFF MDI 320/9.6 μg
  Budensonide, and Formoterol Fumarate
  Other Name: BFF

Study Arms

• Experimental: BGF (PT010) MDI 320/14.4/9.6 μg
  BGF MDI 320/14.4/9.6 μg, Budesonide, Glycopyrronium, Formoterol Fumarate Aerosol (PT010, BGF metered dose inhaler [MDI])
  Intervention: Drug: BGF MDI 320/14.4/9.6 μg
• Experimental: BGF (PT010) MDI 160/14.4/9.6 μg
  BGF MDI 160/14.4/9.6 μg, Budesonide, Glycopyrronium, Formoterol Fumarate Aerosol (PT010, BGF metered dose inhaler [MDI])
  Intervention: Drug: BGF MDI 160/14.4/9.6 μg
• Experimental: BFF (PT009) MDI 320/9.6 μg
  BFF MDI 320/9.6 μg Budesonide, Formoterol Fumarate Aerosol Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT009)
  Intervention: Drug: BFF MDI 320/9.6 μg
• Experimental: GFF (PT003) MDI 14.4/9.6 μg
  GFF MDI 14.4/9.6 μg Glycopyrronium, Formoterol Fumarate Aerosol Budesonide and Formoterol Fumarate Inhalation Aerosol (PT003)
  Intervention: Drug: GFF MDI 14.4/9.6 μg

Publications *

• Singh D, Hurst JR, Martinez FJ, Rabe KF, Bafadhel M, Jenkins M, Salazar D, Dorinsky P, Darken P. Predictive modeling of COPD exacerbation rates using baseline risk factors. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221107314. doi: 10.1177/17534666221107314.
• Rhodes K, Jenkins M, de Nigris E, Aurivillius M, Ouwens M. Relationship between risk, cumulative burden of exacerbations and mortality in patients with COPD: modelling analysis using data from the ETHOS study. BMC Med Res Methodol. 2022 May 25;22(1):150. doi: 10.1186/s12874-022-01616-7.
• Rabe KF, Martinez FJ, Ferguson GT, Wang C, Singh D, Wedzicha JA, Trivedi R, St Rose E, Ballal S, McLaren J, Darken P, Aurivillius M, Reisner C, Dorinsky P; ETHOS Investigators. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med. 2020 Jul 2;383(1):35-48. doi: 10.1056/NEJMoa1916046. Epub 2020 Jun 24.
• Rabe KF, Martinez FJ, Ferguson GT, Wang C, Singh D, Wedzicha JA, Trivedi R, St Rose E, Ballal S, McLaren J, Darken P, Reisner C, Dorinsky P. A phase III study of triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler 320/18/9.6 mug and 160/18/9.6 mug using co-suspension delivery technology in moderate-to-very severe COPD: The ETHOS study protocol. Respir Med. 2019 Oct-Nov;158:59-66. doi: 10.1016/j.rmed.2019.08.010. Epub 2019 Aug 22.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 7, 2020): 8588
• Original Estimated Enrollment (submitted: June 5, 2015): 8000
• Actual Study Completion Date: July 26, 2019
• Actual Primary Completion Date: July 26, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

• Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study.
• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS),
• Current or former smokers with a history of at least 10 pack-years of cigarette smoking.
• Forced expiratory volume in 1 second (FEV1)/Forced vital capacity (FVC) ratio must be <0.70 and FEV1 must be <65% predicted normal value calculated using NHANES III reference equations (or reference norms applicable to other regions).
• Subjects with history of exacerbations.

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

Exclusion Criteria

• Significant diseases or conditions other than COPD, which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study.
• Women who are pregnant or lactating, or are planning to become pregnant during the course of the study, or women of childbearing potential who are not using an acceptable method of contraception.
• Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma.
• Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Visit 1 (Screening)
• Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Visit 1 (Screening)
• Immune suppression or severe neurological disorders affecting control of the upper airway or other risk factors that in the opinion of the Investigator would put the subject at substantial risk of pneumonia.
• Subjects with a diagnosis of narrow angle glaucoma, who, in the opinion of the Investigator, have not been adequately treated.
• Subjects who have a history of hypersensitivity to β2-agonists, budesonide or any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics, or any other component of the IMPs.

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Chile, China, Czechia, France, Germany, Hungary, Italy, Japan, Mexico, Netherlands, New Zealand, Peru, Poland, Russian Federation, Serbia, South Africa, Spain, Sweden, Taiwan, United Kingdom, United States
• Removed Location Countries: Brazil, Korea, Republic of

Administrative Information

• NCT Number: NCT02465567
• Other Study ID Numbers: PT010005
• 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: Not Provided
• Current Responsible Party: Pearl Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Pearl Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Paul M Dorinsky, MD; Pearl Therapeutics

• PRS Account: Pearl Therapeutics, Inc.
• Verification Date: January 2021