Last updated: 08/30/2021 00:00:06

First Time in Human (FTIH) study to evaluate safety, tolerability, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK3511294 administered subcutaneously (SC) in subjects with mild to moderate asthma

GSK study ID
205722
See study documents
Clinicaltrials.gov ID
NCT03287310
See results summary
EudraCT ID
2016-004256-30
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A randomised double-blind (sponsor open), placebo controlled, single ascending dose, First Time in Human study in participants with mild to moderate asthma to assess safety, tolerability, immunogenicity, pharmacokinetics and pharmacodynamics of GSK3511294 administered subcutaneously
Trial description: GSK3511294 is a humanized monoclonal antibody antagonist of Interleukin (IL)-5 which is known to block binding of IL-5 to the IL-5 receptor complex, causing a reduction in the circulating population of eosinophils. This is a single ascending dose FTIH study to investigate safety, tolerability, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK3511294, administered SC in subjects with mild to moderate asthma maintained on a low–medium daily dose of inhaled corticosteroids (ICS) or ICS/long acting beta-agonist (LABA), and short acting beta-agonist (SABA). The subjects will attend a pre-screen visit of up to 12 weeks before dosing for assessment of blood eosinophils. Eligible subjects with blood eosinophils >=200 cells per microliter (cells/µL) will undergo a screening period of up to 4 weeks. The subjects will then be randomized into 5 cohorts. In each cohort, the subjects will be randomized to receive a single dose of GSK3511294 or placebo in a ratio of 3:1. The follow-up period will be up to 40 weeks post dose and will be dose-dependent. The scheduled maximum duration for each subject will be up to 44 weeks including up to 28 days of screening.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of subjects with adverse events (AEs) and serious adverse events (SAEs) in Cohort 1.

Timeframe: Up to Week 32

Number of subjects with AEs and SAEs in Cohort 2

Timeframe: Up to Week 32

Number of subjects with AEs and SAEs in Cohort 3.

Timeframe: Up to Week 36

Number of subjects with AEs and SAEs in Cohort 4.

Timeframe: Up to Week 36

Number of subjects with AEs and SAEs in Cohort 5.

Timeframe: Up to Week 40

Number of subjects with abnormal temperature in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal temperature in Cohort 2.

Timeframe: Up to Week 32

Number of subjects with abnormal temperature in Cohort 3.

Timeframe: Up to Week 36

Number of subjects with abnormal temperature in Cohort 4.

Timeframe: Up to Week 36

Number of subjects with abnormal temperature in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal blood pressure in Cohort 1.

Timeframe: Up to Week 32

Number of subjects with abnormal blood pressure in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal blood pressure in Cohort 3.

Timeframe: Up to Week 36

Number of subjects with abnormal blood pressure in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal blood pressure in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal heart rate in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal heart rate in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal heart rate in Cohort 3

Timeframe: Up to Week 36

Number of subjects with abnormal heart rate in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal heart rate in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal respiratory rate in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal respiratory rate in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal respiratory rate in Cohort 3

Timeframe: Up to Week 36

Number of subjects with abnormal respiratory rate in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal respiratory rate in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal electrocardiogram (ECG) findings in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal ECG findings in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal ECG findings in Cohort 3

Timeframe: Up to Week 36

Number of subjects with abnormal ECG findings in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal ECG findings in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal hematology parameters in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal hematology parameters in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal hematology parameters in Cohort 3

Timeframe: Up to Week 36

Number of subjects with abnormal hematology parameters in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal hematology parameters in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal clinical chemistry parameters in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal clinical chemistry parameters in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal clinical chemistry parameters in Cohort 3

Timeframe: Up to Week 36

Number of subjects with abnormal clinical chemistry parameters in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal clinical chemistry parameters in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal urine parameters in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal urine parameters in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal urine parameters in Cohort 3

Timeframe: Up to Week 36

Number of subjects with abnormal urine parameters in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal urine parameters in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal levels of high sensitivity C-reactive protein (hsCRP) in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal levels of hsCRP in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal levels of hsCRP in Cohort 3

Timeframe: Up to Week 36

Number of subjects with abnormal levels of hsCRP in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal levels of hsCRP in Cohort 5

Timeframe: Up to Week 40

Number of subjects with abnormal levels of complement component 3 (C3) and complement component 4 (C4) in Cohort 1

Timeframe: Up to Week 32

Number of subjects with abnormal levels of complement (C3 and C4) in Cohort 2

Timeframe: Up to Week 32

Number of subjects with abnormal levels of complement (C3 and C4) in Cohort 3

Timeframe: Up to Week 36

Number of subjects with abnormal levels of complement (C3 and C4) in Cohort 4

Timeframe: Up to Week 36

Number of subjects with abnormal levels of complement (C3 and C4) in Cohort 5

Timeframe: Up to Week 40

Secondary outcomes:

Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-inf)] of GSK3511294 after single SC dose in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC(0-inf) of GSK3511294 after single SC dose in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC(0-inf) of GSK3511294 after single SC dose in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC(0-inf) of GSK3511294 after single SC dose in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC(0-inf) of GSK3511294 after single SC dose in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration [AUC (0-t)] of GSK3511294 after single SC dose within a subject in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC (0-t) of GSK3511294 after single SC dose within a subject in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC (0-t) of GSK3511294 after single SC dose within a subject in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC (0-t) of GSK3511294 after single SC dose within a subject in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC (0-t) of GSK3511294 after single SC dose within a subject in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Area under the concentration-time curve from time zero to Week 4 [AUC(0-Week4)] in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC(0-Week4) in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC(0-Week4) in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC(0-Week4) in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC(0-Week4) in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Area under the concentration-time curve from time zero to Week 12 [AUC(0-Week12)] in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC(0-Week12) in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC(0-Week12) in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC(0-Week12) in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC(0-Week12) in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Area under the concentration-time curve from time zero to Week 26 [AUC(0-Week26)] in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC(0-Week26) in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

AUC(0-Week26) in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC(0-Week26) in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

AUC(0-Week26) in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Percentage of AUC(0-INF) obtained by extrapolation [%AUCex] in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

%AUCex in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

%AUCex in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

%AUCex in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

%AUCex in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Maximum observed concentration (Cmax) of GSK3511294 after single SC dose in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

Cmax of GSK3511294 after single SC dose in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

Cmax of GSK3511294 after single SC dose in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

Cmax of GSK3511294 after single SC dose in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

Cmax of GSK3511294 after single SC dose in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Time of occurrence of Cmax (tmax) of GSK3511294 after single SC dose in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

tmax of GSK3511294 after single SC dose in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

tmax of GSK3511294 after single SC dose in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

tmax of GSK3511294 after single SC dose in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

tmax of GSK3511294 after single SC dose in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Time of last quantifiable concentration (tlast) of GSK3511294 after single SC dose in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

tlast of GSK3511294 after single SC dose in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

tlast of GSK3511294 after single SC dose in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

tlast of GSK3511294 after single SC dose in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

tlast of GSK3511294 after single SC dose in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Apparent clearance following subcutaneous dosing (CL/F) of GSK3511294 in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

CL/F of GSK3511294 in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

CL/F of GSK3511294 in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

CL/F of GSK3511294 in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

CL/F of GSK3511294 in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Apparent volume of distribution after subcutaneous administration (Vd/F) of GSK3511294 in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

Vd/F of GSK3511294 in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

Vd/F of GSK3511294 in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

Vd/F of GSK3511294 in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

Vd/F of GSK3511294 in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Terminal elimination rate constant of GSK3511294 in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

Terminal elimination rate constant of GSK3511294 in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

Terminal elimination rate constant of GSK3511294 in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

Terminal elimination rate constant of GSK3511294 in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

Terminal elimination rate constant of GSK3511294 in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Terminal phase half-life (t1/2) of GSK3511294 in Cohort 1

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

t1/2 of GSK3511294 in Cohort 2

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183 post-dose

t1/2 of GSK3511294 in Cohort 3

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

t1/2 of GSK3511294 in Cohort 4

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 253 post-dose

t1/2 of GSK3511294 in Cohort 5

Timeframe: Pre-dose; 2, 8, 24, 48 hours and on Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, Day 183, Day 225, Day 281 post-dose

Ratio to Baseline in absolute blood eosinophil count after SC dose of GSK3511294 in Cohort 1

Timeframe: Up to Week 32

Ratio to Baseline in absolute blood eosinophil count after SC dose of GSK3511294 in Cohort 2

Timeframe: Up to Week 32

Ratio to Baseline in absolute blood eosinophil count after SC dose of GSK3511294 in Cohort 3

Timeframe: Up to Week 36

Ratio to Baseline in absolute blood eosinophil count after SC dose of GSK3511294 in Cohort 4

Timeframe: Up to Week 36

Ratio to Baseline in absolute blood eosinophil count after SC dose of GSK3511294 in Cohort 5

Timeframe: Up to Week 40

Frequency of anti-drug antibody (ADA) binding to GSK3511294 in Cohort 1

Timeframe: Up to Week 32

Frequency of ADA binding to GSK3511294 in Cohort 2

Timeframe: Up to Week 32

Frequency of ADA binding to GSK3511294 in Cohort 3

Timeframe: Up to Week 36

Frequency of ADA binding to GSK3511294 in Cohort 4

Timeframe: Up to Week 36

Frequency of ADA binding to GSK3511294 in Cohort 5

Timeframe: Up to Week 40

Concentration of binding ADAs to GSK3511294 in Cohort 1

Timeframe: Up to Week 32

Concentration of binding ADAs to GSK3511294 in Cohort 2

Timeframe: Up to Week 32

Concentration of binding ADAs to GSK3511294 in Cohort 3

Timeframe: Up to Week 36

Concentration of binding ADAs to GSK3511294 in Cohort 4

Timeframe: Up to Week 36

Concentration of binding ADAs to GSK3511294 in Cohort 5

Timeframe: Up to Week 40

Interventions:
  • Drug: GSK3511294
  • Drug: Placebo
  • Drug: Salbutamol/albuterol
    • Enrollment:
    50
    Primary completion date:
    2019-31-07
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Singh D, Fuhr R, Bird N, Mole S, Hardes K, Man YL, Cahn T, Yancey S, Pouliquen I. A Phase 1 study of the long-acting anti-IL-5 monoclonal antibody GSK3511294 in patients with asthma. Br J Clin Pharmacol. 2021; DOI: 10.1111/bcp.15002 PMID: 34292606
    Medical condition
    Asthma
    Product
    GSK3511294
    Collaborators
    Not applicable
    Study date(s)
    October 2017 to July 2019
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 65 years
    Accepts healthy volunteers
    No
    • Subjects should be between 18 and 65 years of age inclusive, at the time of signing the informed consent.
    • Blood eosinophils of >= 200 cells/µL at screening.
    • Any asthma exacerbation requiring systemic corticosteroids within 12 weeks of screening, or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to screening.
    • A history of life-threatening asthma defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subjects should be between 18 and 65 years of age inclusive, at the time of signing the informed consent.
    • Blood eosinophils of >= 200 cells/µL at screening.
    • A physician diagnosis of asthma (mild or moderate, as defined by the Global Initiative for Asthma [GINA], 2017) at least 12 months prior to the start of the study. The reason for diagnosis of asthma should be documented in the subject’s source data, including relevant history and investigations – specifically evidence of airway hyper-responsiveness, airflow variation (peak flow rate or forced expiratory volume in one second [FEV1]) or reversible airflow obstruction should also be documented in the subject’s source data.
    • A screening pre-bronchodilator FEV1 >= 60% of predicted normal value.
    • Asthma Control Test score > 19.
    • hsCRP of < 10 milligrams per liter (mg/L) at screening.
    • Otherwise healthy (other than the acceptable conditions of asthma and other atopic diseases, including allergic rhinitis and atopic dermatitis) based on a screening medical history, physical examination, vital signs, ECG assessment, pulmonary function testing, and clinical laboratory results.
    • Maintained controlled on as needed SABA and one of the following: a) stable dose of ICS; b) stable dose of combination therapy: ICS/LABA.
    • Body weight >= 50 kilograms (kg), and body mass index (BMI) of 19-32 kilograms per square meter (kg/m^2) inclusive.
    • Male and female subjects. a) a female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential. b) as GSK3511294 is a monoclonal antibody that is not anticipated to interact directly with Deoxyribonucleic acid (DNA) or other chromosomal material with minimal exposure through semen expected, male subjects will not be required to use contraception during the study, nor are they prohibited from donating sperm.
    • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions of the study.
    Exclusion criteria:
    • Any asthma exacerbation requiring systemic corticosteroids within 12 weeks of screening, or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to screening.
    • A history of life-threatening asthma defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
    • Significant pulmonary diseases, other than asthma, including (but not limited to): pneumonia previously requiring hospital admission, pulmonary fibrosis, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other significant respiratory abnormalities.
    • Suspected or confirmed bacterial or viral infection (including tuberculosis) of the upper or lower respiratory tract, sinus or middle ear that occurred within and/or has not resolved within 4 weeks of screening that: led to a change in asthma management or in the opinion of the Investigator, is expected to affect the subject’s asthma status or the subject’s ability to participate in the study.
    • Positive for hepatitis B surface antigen (HBsAg) at screening.
    • Positive hepatitis C antibody test result at screening, or within 3 months prior to first dose of study treatment.
    • Known immunodeficiency (other than that explained by the use of corticosteroids), including a positive test for human immunodeficiency virus (HIV) antibody at screening.
    • Latent or chronic infections (example, genital herpes, urinary tract infections) or at risk of infection (example, significant trauma or infection within the 90 days before screening).
    • Opportunistic infection within 6 months prior to screening (example, a non-tuberculous mycobacterial infection or cytomegalovirus, pneumocystosis, aspergillosis).
    • Parasitic infestation within 6 months prior to screening, or have travelled to a country with a high prevalence of such infections in the 6 months before screening, or intend to do so in the year after dosing.
    • Live vaccine within 4 weeks prior to screening, or intention to receive live vaccine during the study.
    • Corrected QT by Fridericia’s formula (QTcF) interval > 450 milliseconds (msec)
    • A personal history of severe hypertension, arrhythmia, Right Bundle Branch Block, or Left Bundle Branch Block, or a family history of sudden unexplained death, long QT, familial cardiac syndrome, or cardiomyopathy.
    • ALT >1.5 times upper limit of normal (ULN).
    • Bilirubin >1.5 times ULN. Isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
    • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
    • Any history or presence of clinically relevant cardiac or cardiovascular, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease or immunodeficiency, or signs of acute illness, or any other illness or condition that, in the opinion of the investigator (in consultation with the medical monitor), would adversely affect the subject’s participation in this study.
    • A previous history of cancer in remission for less than 5 years prior to screening (except for localized carcinoma of the skin that had been resected for cure) or current malignancy.
    • A positive drug/alcohol test before dosing, OR any history of drug abuse OR regular alcohol consumption within 6 months of the study defined as: An average weekly intake of > 14 units alcohol. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (equivalent to 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
    • Current smokers or ex-smokers who have given up smoking for < 12 months and/or have a smoking pack history of > 5 pack years (1 pack year = 20 cigarettes per day for 1 year or 5 cigarettes per day for 4 years).
    • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
    • Anticipated non-availability and/or risk of non-compliance with study visits and procedures, or unwillingness or inability to follow the study specific procedures.
    • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
    • Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
    • History of sensitivity to any of the study medications, or its components, or a history of drug reaction or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
    • Major surgery within 90 days prior to screening, or planned in-patient surgery or hospitalization during the study period
    • Donation or loss of blood or blood products in excess of 500 mL within the 3 months before dosing.
    • History of renal disease, abnormal kidney function or evidence of persisting or clinically relevant protein or blood on urinalysis.
    • History or signs of immunologically active disease (including the presence of low C3 or low C4) or thrombocytopenia.
    • History of vasculitis.
    • Subjects are excluded if they are undergoing desensitization therapy, or have received any of the following medications as indicated prior to screening: anti- Immunoglobulin E (IgE) therapy (within 6 months); anti-IL5 (within 6 months); oral or injectable corticosteroids (within 8 weeks); long acting muscarinic antagonist (LAMA) or leukotriene receptor antagonist (LTRA) therapy (within 8 weeks); drugs that can prolong the QT interval.
    • Subjects who are employees of the sponsor or clinical unit are excluded.
    • Vulnerable subjects, e.g., participants kept in detention, protected adults under guardianship, trusteeship and soldiers, or participants committed to an institution by governmental or juridical order.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Berlin, Berlin, Germany, 14050
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Hannover, Niedersachsen, Germany, 30625
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Harrow, Middlesex, United Kingdom, HA1 3UJ
    Status
    Study Complete
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    Location
    GSK Investigational Site
    London, United Kingdom, NW10 7EW
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Manchester, United Kingdom, M23 9QZ
    Status
    Study Complete
    Contact us

    Study documents

    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2019-31-07
    Actual study completion date
    2019-31-07

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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