A Study of GSK3511294 (Depemokimab) Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype (NIMBLE)

• ClinicalTrials.gov Identifier: NCT04718389
• Recruitment Status: Recruiting
• First Posted: January 22, 2021
• Last Update Posted: February 27, 2023
• Sponsor: GlaxoSmithKline
• Collaborator: Iqvia Pty Ltd
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: January 18, 2021
• First Posted Date: January 22, 2021
• Last Update Posted Date: February 27, 2023
• Actual Study Start Date: January 26, 2021
• Estimated Primary Completion Date: November 27, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2021)

Annualized rate of clinically significant exacerbations over 52 weeks [ Time Frame: Up to Week 52 ]

Clinically significant exacerbations of asthma are defined by worsening of asthma which requires use of systemic corticosteroids and/or hospitalization and/or Emergency Department (ED) visit. Annualized rate of exacerbations will be calculated as number of exacerbations experienced by the participant divided by the length of time the participant is measured on.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 18, 2021)

• Weighted mean change from Baseline in St. George's Respiratory Questionnaire (SGRQ) total score [ Time Frame: Baseline (Day 1) and up to Week 52 ]
  The SGRQ is a well-established instrument, comprising 51 questions designed to measure Quality of Life in participants with diseases of airway obstruction. Higher score indicates worse quality of life.
• Weighted mean change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score [ Time Frame: Baseline (Day 1) and up to Week 52 ]
  The ACQ-5 is a five-item questionnaire, which has been developed as a measure of participants' asthma control that can be quickly and easily completed. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze) over the previous week. The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/ limitation) scale. Higher score indicates more limitations.
• Weighted mean change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
  FEV1 is a measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 will be measured using spirometry.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of GSK3511294 (Depemokimab) Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype
• Official Title: A 52-week, Randomised, Double-blind, Double-dummy, Parallel Group, Multi-centre, Non-inferiority Study Assessing Exacerbation Rate, Additional Measures of Asthma Control and Safety in Adult and Adolescent Severe Asthmatic Participants With an Eosinophilic Phenotype Treated With GSK3511294 Compared With Mepolizumab or Benralizumab
• Brief Summary: This study will assess whether switching participants who have benefitted from mepolizumab or benralizumab to GSK3511294 (Depemokimab) is non-inferior to maintaining current treatment on the annualized rate of clinically significant exacerbations in participants with severe asthma with an eosinophilic phenotype. Throughout the study, all participants will continue their non-biologic Baseline standard of care (SoC) asthma treatment.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

This is randomized, double-blind, parallel group, multi-center and non-inferiority study.

Masking: Double (Participant, Investigator)
Masking Description:

This is a double-blind study.

Primary Purpose: Treatment

• Condition: Asthma

Intervention

• Biological: GSK3511294 (Depemokimab)
  GSK3511294 (Depemokimab) will be provided in a single-use prefilled syringe (PFS).
• Biological: Mepolizumab
  Mepolizumab will be provided in a single-use PFS.
• Biological: Benralizumab
  Benralizumab will be provided in a single-use PFS.
• Biological: Placebo
  Placebo will be a sterile liquid formulation.
• Drug: Standard of care (SoC)
  Non-biologic SoC will include inhaled corticosteroid (ICS) plus at least one other controller, long-acting beta-2-agonist (LABA), long-acting muscarinic antagonist (LAMA), with or without maintenance oral corticosteroids (OCS).
• Device: Pre-filled Syringes (PFS)
  PFS will include glass barrel with pre-staked needle and plunger.

Study Arms

• Experimental: Participants receiving GSK3511294 (Depemokimab) plus placebo matching prior anti-IL-5/5R treatment
  Participants will receive GSK3511294 (Depemokimab) plus placebo treatment matching the active comparator (participant's anti-Interleukin-5/ 5 receptor [anti-IL-5/5R] treatment prior to randomization): either placebo matching mepolizumab or placebo matching benralizumab. All participants will continue their non-biologic Baseline SoC asthma treatment throughout the study.
  Interventions:

  • Biological: GSK3511294 (Depemokimab)
  • Biological: Placebo
  • Drug: Standard of care (SoC)
  • Device: Pre-filled Syringes (PFS)
• Active Comparator: Participants receiving prior anti-IL-5/5R treatment plus placebo matching GSK3511294 (Depemokimab)
  Participants will receive active comparator (participant's anti-IL-5/5R treatment prior to randomization): either mepolizumab or benralizumab, plus placebo matching GSK3511294 (Depemokimab). All participants will continue their non-biologic Baseline SoC asthma treatment throughout the study.
  Interventions:

  • Biological: Mepolizumab
  • Biological: Benralizumab
  • Biological: Placebo
  • Drug: Standard of care (SoC)
  • Device: Pre-filled Syringes (PFS)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 18, 2021): 1700
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 27, 2024
• Estimated Primary Completion Date: November 27, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key inclusion criteria for study:

• Adult and adolescent participants more than or equal to (>=)12 years of age, at the time of signing the informed consent/assent.
• Participants who have a documented physician diagnosis of asthma for >=2 years that meets the National Heart, Lung, and Blood Institute guidelines (NHLBI) or Global Initiative for Asthma (GINA) guidelines.

• Participants receiving either mepolizumab 100 milligrams (mg) or benralizumab 30 mg for >=12 months prior to screening and have a documented benefit to therapy assessed by either:

  (i) >=50% reduction in exacerbation frequency since initiating treatment, or (ii) >=50% reduction in maintenance OCS use since initiating treatment, or (iii) No exacerbations in the past 6 months whilst receiving anti-IL-5/5R therapy and an Asthma Control Questionnaire (ACQ)-5 score of less than or equal to (<=)1.5 at screening.

• A well-documented requirement for regular treatment with medium to high dose ICS in the 12 months prior to Visit 1 with or without maintenance OCS. The maintenance ICS dose must be >=440 micrograms (mcg) fluticasone propionate (FP) hydrofluoroalkane (HFA) product daily, or clinically comparable. Participants who are treated with medium dose ICS will also need to be treated with a LABA to qualify for inclusion.
• Current treatment with at least one additional controller medication, besides ICS [for example (e.g.), LABA, LAMA, leukotriene receptor antagonist (LTRA), or theophylline].

Key exclusion criteria for study:

• Participants with presence of a known pre-existing, clinically important lung condition other than asthma. This includes (but is not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
• Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis.
• A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded).
• Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
• Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis excluded prior to enrolment.
• Participants who have received Omalizumab (Xolair), dupilumab (Dupixent) or reslizumab (Cinqair/Cinqaero) within 130 days prior to Visit 1.
• Participants who have received any Monoclonal antibody (mAb) within 5 half-lives of Visit 1.
• Corrected QT interval using Fridericia's formula (QTcF) >=450 milliseconds (msec) or QTcF >=480 msec for participants with Bundle Branch Block at screening Visit 1.
• Current smokers or former smokers with a smoking history of >=10 pack years (number of pack years equal to [number of cigarettes per day/20] times number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1.
• Participants with allergy/intolerance to a mAb or biologic.

Key exclusion criteria for randomization:

• Evidence of a clinically significant abnormality in the 12-lead electrocardiogram (ECG) over-read conducted at Screening Visit 1, based on the evaluation of the investigator, or QTcF >=450 msec or QTcF >=480 msec for participants with Bundle Branch Block, at randomization Visit 2.
• Participants with a clinically significant asthma exacerbation in the 7 days prior to randomization should have their randomization visit delayed until the investigator considers the participant's asthma to be stable. If the 8-week screening period has elapsed, then the participant should be considered a run-in failure.
• Any changes in the dose or regimen of Baseline ICS and/or additional controller medication (except for treatment of an exacerbation) during the run-in period.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

• Listed Location Countries: Australia, Austria, Canada, Finland, France, Germany, Ireland, Italy, Japan, Netherlands, Norway, Poland, Puerto Rico, Slovenia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04718389
• Other Study ID Numbers: 206785
• 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: Yes

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, key secondary endpoints and safety data 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: Iqvia Pty Ltd

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: February 2023