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A 52-week, Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Study of the Efficacy and Safety of GSK3511294 Adjunctive Therapy in Adult and Adolescent Participants With Severe Uncontrolled Asthma With an Eosinophilic Phenotype

A Study of GSK3511294 in Participants With Severe Asthma With an Eosinophilic Phenotype

397

The baseline characteristics of participants in this study were as follows. - A total of 380 subjects were enrolled, with 252 in the GSK3511294 group and 128 in the placebo group. The mean age of participants was 53.6 years [Standard Deviation (SD): 16.00] in the GSK3511294 group and 51.2 years (SD: 16.58) in the placebo group, resulting in an overall mean age of 52.8 years (SD: 16.22). - The proportion of female participants was 63.5% (n=160) in the GSK3511294 group and 63.3% (n=81) in the placebo group, making up 63.4% (n=241) of the total population, while male participants accounted for 36.5% (n=92) and 36.7% (n=47) in each group, respectively, with a total of 36.6% (n=139). - Regarding racial distribution, 20.6% (n=52) of participants in the GSK3511294 group and 18% (n=23) in the placebo group were Asian, totaling 19.7% (n=75) in overall population. 71.8% (n=181) of the GSK3511294 group and 71.1% (n=91) of the placebo group are White, totaling 71.6% (n=272) in overall population. Participants categorized as "Others" is 7.5% (n=19) in the GSK3511294 group and 10.9% (n=14) in the placebo group, totaling 8.7% (n=33) in overall population.

In this study, 263 participants were randomized to receive GSK3511294 and 134 participants were randomized to receive placebo. The full analysis population included 252 patients in the GSK3511294 group and 128 participants in the placebo group. 233 participants in the GSK3511294 group and 117 participants in the placebo group completed the study. 30 participants in the GSK3511294 group and 17 participants in the placebo group discontinued the study. Reasons why some participants in both the GSK3511294 and placebo groups discontinued the study are follows: the number of participants who discontinued due to adverse events was one in each group. Discontinuation due to lack of efficacy occurred in four participants in the GSK3511294 group and one in the placebo group. Two participants in each group were lost to follow-up. Discontinuation based on physician decision was reported in two participants in the GSK3511294 group and none in the placebo group. One participant in the placebo group discontinued due to pregnancy, while none did in the GSK3511294 group. Withdrawal by the participants was reported in ten participants in the GSK3511294 group and six in the placebo group. Participants who were randomized but not treated included four in the GSK3511294 group and one in the placebo group. Discontinuation due to GCP violations occurred in seven participants in the GSK3511294 group and five in the placebo group.

In this study, no deaths were reported in either the GSK3511294 group (0.00%) or the placebo group (0.00%). Serious adverse events (SAEs) were observed in 7.57% (19/251) of subjects in the GSK3511294 group and 10.08% (13/129) of subjects in the placebo group. Details are provided in the other attachment file 1.

The annualized rate of clinically significant exacerbation over 52 weeks [95% confidence interval (95%CI)] in each treatment group is 0.56 (0.44, 0.70) in GSK3511294 group and 1.08 (0.83, 1.41) in placebo group, respectively. Rate ratio (95%CI) is 0.52(95% CI: 0.36, 0.73; P-value<0.001). - Improvements in St. George's Respiratory Questionnaire (SGRQ) total scores were observed in both GSK3511294 and placebo groups with a numerically greater improvement in the GSK3511294 group at Week 52 [-14.80 (1.041) vs. -12.49 (1.455)]. The treatment difference between GSK3511294 and placebo groups was -2.31 (95% CI: -5.84, 1.23; P-value= 0.200). - At Week 52, the LS mean (SE) change from baseline in Asthma Control Questionnaire-5 (ACQ-5) score was -0.81 (0.065) in the GSK3511294 group and -0.70 (0.091) in the placebo group. The treatment difference between GSK3511294 and placebo groups was -0.11 (95% CI: -0.33, 0.11; P value= 0.333). - At Week 52, the LS mean (SE) change from baseline in improvement in pre-bronchodilator FEV1 was 0.240 (0.0286) L in the GSK3511294 group and 0.184 (0.0407) L in the placebo group. The treatment difference between GSK3511294 and placebo groups was 0.056 L (95% CI: -0.043, 0.154; P-value= 0.267). - At Week 52, the LS mean (SE) change from baseline in ANSD weekly score was -1.18 (0.091) in the GSK3511294 group and -0.97 (0.127) in the placebo group. The treatment difference between GSK3511294 and placebo groups was -0.21 (95% CI: -0.52, 0.09; P value=0.173). - At Week 52, the LS mean (SE) change from baseline in ADSD weekly score was -1.13 (0.080) in the GSK3511294 group and -0.93 (0.112) in the placebo group. The treatment difference between GSK3511294 and placebo groups was -0.21 (95% CI: 0.48, 0.07; P value=0.138). - The proportion of participants experiencing exacerbations requiring hospitalization and/or an Emergency Department (ED) visit was lower among participants receiving GSK3511294 resulting in a 58% reduction (rate ratio: 0.42; 95% CI: 0.16, 1.13; P value=0.087).

Study 213744 was a 52-week, Phase 3 clinical trial designed to evaluate the efficacy and safety of GSK3511294 as an adjunctive therapy for adults and adolescents with severe uncontrolled asthma exhibiting an eosinophilic phenotype to assess the effectiveness of GSK3511294 100 mg administered subcutaneously every 26 weeks compared to placebo. The primary endpoint demonstrated a statistically significant reduction in exacerbation rates for GSK3511294 compared to placebo.

April. 11, 2025

Dec. 19, 2024

https://pubmed.ncbi.nlm.nih.gov/39248309/

Yes

[Plan Description] IPD for this study will be made available via the Clinical Study Data Request site. [URL] http://clinicalstudydatarequest.com

https://jrct.mhlw.go.jp/latest-detail/jRCT2031200411

Miyazato Atsuko

IQVIA Services Japan G.K.

4-10-18 Takanawa, Minato-ku, Tokyo

213744_JAPAN_jRCT@iqvia.com

Ayabe Takaaki

IQVIA Services Japan G.K.

4-10-18 Takanawa, Minato-ku, Tokyo

+81-120-229-053

213744_JAPAN_jRCT@iqvia.com

Complete

Mar. 20, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Adults and adolescents >=12 years of age, at the time of signing the informed consent/assent.
- Participants must have a documented physician diagnosis of asthma for >=2 years that meets the National Heart, Lung, and Blood Institute guidelines (NHLBI, 2007) or Global Initiative for Asthma (GINA) guidelines (GINA, 2020) and (a) Eosinophilic phenotype: participants who have, or with high likelihood of having, asthma with an eosinophilic phenotype as per randomization criteria, and (b) Exacerbation history: participants who have previously confirmed history of >=2 exacerbations requiring treatment with systemic corticosteroid (CS) (Intramuscular [IM], Intravenous [IV], or oral), in the 12 months prior to Visit 1, despite the use of medium to high-dose ICS. For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.
- Persistent airflow obstruction as indicated by (i) For participants >=18 years of age at Visit 1, a pre-bronchodilator FEV1 <80 percent predicted National Health and Nutrition Examination Survey (NHANES III) recorded at Visit 1 (ii)For participants 12-17 years of age at Visit 1: A pre-bronchodilator FEV1 <90 percent predicted (NHANES III) recorded at Visit 1 or FEV1: Forced Vital Capacity (FVC) ratio <0.8 recorded at Visit 1.
- 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 fluticasone propionate (FP) hydrofluoroalkane product (HFA) daily, or clinically comparable (GINA, 2020). Participants who are treated with medium dose ICS will also need to be treated with LABA to qualify for inclusion.
- Current treatment with at least one additional controller medication, besides ICS, for at least 3 months (e.g., LABA, LAMA, leukotriene receptor antagonist [LTRA], or theophylline).

<For randomization>
- An elevated peripheral blood eosinophil count of >=300 cells per microliter demonstrated in the past 12 months prior to Visit 1 that is related to asthma or an elevated peripheral blood eosinophil count of >=150 cells per microliter at Screening Visit 1 that is related to asthma.
- Evidence of airway reversibility or responsiveness as documented by either: (i) Airway reversibility (FEV1>=12 percent and 200 milliliter [mL]) demonstrated at Visit 1 or Visit 2 using the Maximum Post Bronchodilator Procedure or (ii)Airway reversibility (FEV1>=12 percent and 200 mL) documented in the 12 months prior to Visit 2 (randomization visit) or (iii) Airway hyperresponsiveness (methacholine: Provocative concentration causing a 20 percent fall in FEV1 [PC20] of <8 milligrams per milliliter (mg/mL), histamine: Provocative dose that decreases FEV1 by 20 percent [PD20] of <7.8 micromoles, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 12 months prior to Visit 2 (randomization visit).

- 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 who have known, pre-existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment.
- Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment.
- Participants who have received mepolizumab, reslizumab, or benralizumab within 12 months prior to Visit 1 or who have a previous documented failure with Anti-Interleukin-5/ Anti-Interleukin-5 receptor (anti-IL-5/5R) therapy.
- Participants who have received omalizumab or dupilumab within 130 days prior to Visit 1.
- Participants who have received any monoclonal antibody (mAb) within 5 half-lives of Visit 1.
- Previously participated in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 12 months prior to 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 = [number of cigarettes per day/ 20] multiplied by 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 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.
- 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.

Both

asthma

Biological: GSK3511294
GSK3511294 will be provided in a single-use prefilled syringe.

Biological: Placebo
Placebo will be available as normal saline in a single-use prefilled syringe.

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.

+81-45-701-9581

Mar. 23, 2021

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