INTREPID: Investigation of TRELEGY Effectiveness: Usual Practice Design

• ClinicalTrials.gov Identifier: NCT03467425
• Recruitment Status: Completed
• First Posted: March 16, 2018
• Results First Posted: September 7, 2020
• Last Update Posted: September 7, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: February 2, 2018
• First Posted Date: March 16, 2018
• Results First Submitted Date: August 19, 2020
• Results First Posted Date: September 7, 2020
• Last Update Posted Date: September 7, 2020
• Actual Study Start Date: April 11, 2018
• Actual Primary Completion Date: October 10, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 19, 2020)

Number of Responders and Non-responders Based on the Chronic Obstructive Pulmonary Disease Assessment Test (CAT) at Week 24 and Number of Participants With Imputed CAT Score at Week 24 [ Time Frame: At Week 24 ]

The CAT is a 8-item questionnaire, used to measure the health status of par. with COPD. Par. rated their experience on a 6-point scale: 0 (no impact) to 5 (maximum impact). CAT score was calculated by summing the non-missing scores of the 8 items with a range of 0-40. Higher scores indicate greater disease impact. Responders were par. who had a change from Baseline score >=2 at Week 24. Non-responders were the par. who had change from Baseline score <2 at Week 24. Change from Baseline was calculated as Week 24 value minus the Baseline value (Day 1). A composite strategy was applied when intercurrent events of randomized treatment modification, change in pulmonary rehabilitation or start of oxygen therapy occurred, otherwise a treatment policy strategy was applied. Missing Week 24 CAT data were imputed assuming missing at random and are presented in a separate category. Number of responders, non-responders based on CAT and par. with imputed CAT score at Week 24 are presented.

Original Primary Outcome Measures (submitted: March 9, 2018)

Number of responders based on CAT at Week 24 [ Time Frame: Week 24 ]

The CAT is a subject-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual subject. The CAT consists of eight items, each formatted on a semantic differential scale. Subjects rated their experience on a 6-point scale for each question, ranging from 0 to 5 with a maximum total score of 40. Higher scores indicate greater disease impact. CAT of each subject was assessed at Baseline (Week 1) and Week 24 or Early withdrawal. Responders are the subjects who will have the change from Baseline of CAT score >=2 at Week 24. Number of responders based on CAT at Week 24 will be presented.

Current Secondary Outcome Measures (submitted: August 19, 2020)

• Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 24 [ Time Frame: Baseline (Day 1) and at Week 24 ]
  FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 measurements were collected using a spirometer. Baseline was defined as the value recorded at Day 1. Change from Baseline was calculated as FEV1 value at Week 24 minus the Baseline value. A treatment policy strategy was used for the intercurrent events of randomized treatment discontinuation, randomized treatment modification, change of pulmonary rehabilitation status and start of oxygen therapy. Only those participants with non-missing covariates were included in the analysis.
• Percentage of Participants Making at Least 1 Critical Error in Inhalation Technique at Week 24 [ Time Frame: At Week 24 ]
  Participants were trained on the correct use of their inhaler devices. All participants who had spirometry measured were to have an assessment of inhaler errors. During the assessment, participants were asked to demonstrate inhaler use when taking their regular dose of medication. A critical error is defined as an error that is most likely to result in no or significantly reduced medication being inhaled. These errors were recorded in an error checklist, during the assessment. A hypothetical strategy was used for the intercurrent event of randomized treatment modification. Percentage of participants making at least 1 critical error in inhalation technique at the Week 24 is presented.

Original Secondary Outcome Measures (submitted: March 9, 2018)

• Change from Baseline in forced expiratory volume in 1 second (FEV1) at Week 24 [ Time Frame: Baseline and Week 24 ]
  FEV1 is the volume of air that can be forced out in one second after taking a deep breath, an important measure of pulmonary function. FEV1 measurements will be obtained using spirometer. For FEV1 determination, at least 3 acceptable spirometry efforts (with no more than 8) should be obtained. The largest FEV1 from the 3 acceptable efforts should be recorded, even if they do not come from the same effort. Baseline was Week 1. Change from Baseline is the difference between Baseline value and post-Baseline value.
• Number of subjects making at least 1 critical error in inhalation technique at Week 24 [ Time Frame: Week 24 ]
  At the start of the study, and whenever subjects are issued with a prescription for a new COPD maintenance therapy, the physician (or delegate) will train the subject on the correct use of their inhaler device(s). A critical error is defined as an error that is most likely to result in no or significantly reduced medication being inhaled. If subjects are unable to perform spirometry they may still participate in the critical error assessment. All subjects who have spirometry measured will also have an assessment of critical errors if an appropriate error checklist is available for the study medication they are using for COPD maintenance therapy at Week 24/Early withdrawal visit. Percentage of subjects making at least 1 critical error in inhalation technique at the Week 24 will be presented.

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

Descriptive Information

• Brief Title: INTREPID: Investigation of TRELEGY Effectiveness: Usual Practice Design
• Official Title: The Clinical Effectiveness of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in a Single Inhaler (TRELEGY™ ELLIPTA™) When Compared With Non-ELLIPTA Multiple Inhaler Triple Therapies in COPD Patients Within a Usual Care Setting
• Brief Summary: The primary purpose of this study is to assess the effectiveness of TRELEGY ELLIPTA relative to non-ELLIPTA Multiple Inhaler Triple Therapies (MITT) for Chronic Obstructive Pulmonary Disease (COPD) control within the usual clinical practice setting. The study will be conducted once TRELEGY ELLIPTA has been approved in the countries in which the study will be conducted and is available commercially. This is a randomized, open-label, effectiveness, phase 4 study of 24 weeks' duration in COPD subjects to evaluate TRELEGY ELLIPTA (fluticasone furoate [FF]/vilanterol [VI]/umeclidinium bromide [UMEC]: 100 microgram [mcg]/62.5 mcg/25 mcg) inhalation powder taken once daily using a single ELLIPTA inhaler compared with any non-ELLIPTA MITT in the usual care setting. Effectiveness of TRELEGY ELLIPTA will be assessed by comparing proportion of COPD Assessment Test (CAT) responders at Week 24 between two treatment groups. TRELEGY and ELLIPTA are trademarks of GlaxoSmithKline (GSK) group of companies. The study will enroll approximately 3000 subjects.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Subjects will be randomized in a ratio of 1:1 to receive one of the following study treatment regimens: TRELEGY ELLIPTA once daily in the morning or Non-ELLIPTA MITT twice-daily treatment.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Pulmonary Disease, Chronic Obstructive

Intervention

• Drug: FF/UMEC/VI
  FF is a dry white powder containing 100 mcg GW685698 blended with lactose in one blister in the first strip of the DPI. UMEC/VI is a dry white powder containing 62.5 mcg of UMEC and 25 mcg of VI per blister, both blended together with lactose and magnesium stearate in the second strip of the DPI.
• Drug: Inhaled Corticosteroid
  Inhaled Corticosteroid (ICS) as prescribed by the physician.
• Drug: LAMA
  LAMA as prescribed by the physician.
• Drug: LABA
  LABA as prescribed by the physician.
• Drug: COPD rescue medications
  Rescue medications for COPD will be prescribed and obtained according to usual practice.

Study Arms

• Experimental: TRELEGY ELLIPTA (FF/UMEC/VI: 100 mcg/62.5 mcg/25 mcg)
  Eligible subjects will receive a blended combination of FF in the first strip (100 mcg per blister) and UMEC/VI in second strip (62.5 mcg UMEC per blister and 25 mcg VI per blister), a single inhalation once daily in the morning in the same TRELEGY ELLIPTA Dry Powder Inhaler (DPI) via inhalation route for a period of 24 weeks. Study treatment may be augmented with other prescribed COPD medications such as including rescue medications, which will be prescribed and obtained according to usual practice.
  Interventions:

  • Drug: FF/UMEC/VI
  • Drug: COPD rescue medications
• Active Comparator: Non-ELLIPTA MITT
  Eligible subjects will receive the ICS/LAMA/LABA products twice daily and dosing regimens as prescribed by their physician for a period of 24 weeks. Study treatment may be augmented with other prescribed COPD medications such as including rescue medications, which will be prescribed and obtained according to usual practice.
  Interventions:

  • Drug: Inhaled Corticosteroid
  • Drug: LAMA
  • Drug: LABA
  • Drug: COPD rescue medications

• Publications *: Worsley S, Snowise N, Halpin DMG, Midwinter D, Ismaila AS, Irving E, Sansbury L, Tabberer M, Leather D, Compton C. Clinical effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol in usual practice: the COPD INTREPID study design. ERJ Open Res. 2019 Nov 4;5(4). pii: 00061-2019. doi: 10.1183/23120541.00061-2019. eCollection 2019 Oct.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 19, 2020): 3109
• Original Estimated Enrollment (submitted: March 9, 2018): 3000
• Actual Study Completion Date: October 10, 2019
• Actual Primary Completion Date: October 10, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Capable of giving signed informed consent.
• Subjects with a documented physician diagnosis of COPD.
• A score of >=10 on the CAT at screening.
• Subjects who have a history of treatment with systemic/oral corticosteroids, antibiotics and/or hospitalization for at least one COPD exacerbation in the 3 years prior to randomization. This will be captured through subject recall and/or medical records and must be documented in subject's notes. Prior use of systemic/oral corticosteroids and/or antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD.
• Subjects currently receiving one of the non-ELLIPTA maintenance therapies listed below who have been prescribed it continually for at least 16 weeks prior to randomization. Continuous prescription is defined as a minimum of 60 days' prescription cover during the prior 16 weeks. The non-ELLIPTA maintenance therapy must be one of the following: Inhaled Corticosteroid (ICS) in combination with Long-acting Muscarinic Receptor Antagonist (LAMA) and Long Acting Beta-Agonist (LABA) (MITT) or LAMA and LABA used in combination as a dual therapy or LABA and ICS used in combination as a dual therapy. Subjects who are currently on a dual maintenance therapy for COPD must be considered by their physician to require a step-up to triple therapy. The reason for the physician decision to step- up must be documented. Subjects who are receiving only COPD medication on an 'as required' basis are not eligible.
• Subjects must be aged >=40 years of age at the time of signing the informed consent.

Exclusion Criteria:

• Women of child bearing potential: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Subjects with any life-threatening condition i.e. low probability, in the opinion of the investigator, of 6-month survival due to severity of COPD or comorbid condition.
• Subjects with resolution of an exacerbation less than 2 weeks prior to visit 1, must not be randomized. Subjects may be rescreened 2 weeks after resolution of exacerbation (exacerbation is defined by treatment with systemic corticosteroids and/or antibiotic).
• Subjects with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the effectiveness or safety analysis if the disease/condition exacerbated during the study.
• A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator contraindicates study participation.
• Subjects who, in the opinion of the treating investigator, are chronic users of oral corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening). Chronic use is defined as more than 14 days continuous use during the 12 weeks prior to visit 1.
• Subjects taking any investigational drug treatment within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study (whichever is the longer of the two).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Netherlands, Spain, Sweden, United Kingdom

Administrative Information

• NCT Number: NCT03467425
• Other Study ID Numbers: 206854; 2017-004369-29 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• URL: http://clinicalstudydatarequest.com

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

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: July 2020