Non-inferiority study of GSK3511294 compared with mepolizumab or benralizumab in participants with severe asthma with an eosinophilic phenotype

JRCT ID: jRCT2031200414

Registered date:11/03/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: asthma
• Date of first enrollment: 20/03/2021
• Target sample size: 1700
• Study type: Interventional

Intervention(s)

Biological: GSK3511294
GSK3511294 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 0.9% sodium chloride solution contained in a PFS.

Outcome(s)

Primary Outcome

Annualized rate of clinically significant exacerbations over 52 weeks
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.

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- 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].

Exclude criteria

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.

<For randomisation>
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.

Related Information

• Primary Sponsor: Hirashima Aki
• Secondary ID(s): NCT04718389