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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: GSK3511294; Drug: Salbutamol/albuterol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • GSK Investigational Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, NW10 7EW
    • GSK Investigational Site
  • Manchester, United Kingdom, M23 9QZ
    • GSK Investigational Site
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects receiving GSK3511294 in Cohort 1; Six subjects in Cohort 1 will receive a single SC dose of 2 mg GSK3511294.	Drug: GSK3511294; GSK3511294 will be available as a clear or opalescent, colorless or yellow to brown solution for injection at unit dose strength of 150 milligrams per milliliter (mg/mL). GSK3511294 will be diluted in 0.9% weight by volume (w/v) sodium chloride to achieve the desired concentration for administration. GSK3511294 will be administered by SC injection.; Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.
Placebo Comparator: Subjects receiving placebo in Cohort 1; Two subjects in Cohort 1 will receive a single SC dose of placebo.	Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.; Drug: Placebo; Matching Placebo will consist of 0.9% w/v sodium chloride which will be administered by the SC route.
Experimental: Subjects receiving GSK3511294 in Cohort 2; Six subjects in Cohort 2 will receive a single SC dose of 10 mg GSK3511294.	Drug: GSK3511294; GSK3511294 will be available as a clear or opalescent, colorless or yellow to brown solution for injection at unit dose strength of 150 milligrams per milliliter (mg/mL). GSK3511294 will be diluted in 0.9% weight by volume (w/v) sodium chloride to achieve the desired concentration for administration. GSK3511294 will be administered by SC injection.; Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.
Placebo Comparator: Subjects receiving placebo in Cohort 2; Two subjects in Cohort 2 will receive a single SC dose of placebo.	Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.; Drug: Placebo; Matching Placebo will consist of 0.9% w/v sodium chloride which will be administered by the SC route.
Experimental: Subjects receiving GSK3511294 in Cohort 3; Nine subjects in Cohort 3 will receive a single SC dose of 30 mg GSK3511294.	Drug: GSK3511294; GSK3511294 will be available as a clear or opalescent, colorless or yellow to brown solution for injection at unit dose strength of 150 milligrams per milliliter (mg/mL). GSK3511294 will be diluted in 0.9% weight by volume (w/v) sodium chloride to achieve the desired concentration for administration. GSK3511294 will be administered by SC injection.; Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.
Placebo Comparator: Subjects receiving placebo in Cohort 3; Three subjects in Cohort 3 will receive a single SC dose of placebo.	Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.; Drug: Placebo; Matching Placebo will consist of 0.9% w/v sodium chloride which will be administered by the SC route.
Experimental: Subjects receiving GSK3511294 in Cohort 4; Nine subjects in Cohort 4 will receive a single SC dose of 100 mg GSK3511294.	Drug: GSK3511294; GSK3511294 will be available as a clear or opalescent, colorless or yellow to brown solution for injection at unit dose strength of 150 milligrams per milliliter (mg/mL). GSK3511294 will be diluted in 0.9% weight by volume (w/v) sodium chloride to achieve the desired concentration for administration. GSK3511294 will be administered by SC injection.; Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.
Placebo Comparator: Subjects receiving placebo in Cohort 4; Three subjects in Cohort 4 will receive a single SC dose of placebo.	Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.; Drug: Placebo; Matching Placebo will consist of 0.9% w/v sodium chloride which will be administered by the SC route.
Experimental: Subjects receiving GSK3511294 in Cohort 5; Six subjects in Cohort 5 will receive a single SC dose of 300 mg GSK3511294.	Drug: GSK3511294; GSK3511294 will be available as a clear or opalescent, colorless or yellow to brown solution for injection at unit dose strength of 150 milligrams per milliliter (mg/mL). GSK3511294 will be diluted in 0.9% weight by volume (w/v) sodium chloride to achieve the desired concentration for administration. GSK3511294 will be administered by SC injection.; Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.
Placebo Comparator: Subjects receiving placebo in Cohort 5; Two subjects in Cohort 5 will receive a single SC dose of placebo.	Drug: Salbutamol/albuterol; Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.; Drug: Placebo; Matching Placebo will consist of 0.9% w/v sodium chloride which will be administered by the SC route.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious AEs (SAE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before; is associated with liver injury and impaired liver function.	Up to Week 40
Number of Participants With Adverse Events of Special Interest (AESI)	AESIs were defined as Hypersensitivity (narrow) and Injection site reactions like hematoma and swelling.	Up to Week 40
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count	Blood samples were collected at indicated time-points for analysis of hematology parameters like platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Red Blood Cell Count (RBC)	Blood samples were collected at indicated time-points for analysis of hematology parameters like RBC count. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Mean Corpuscle Volume (MCV)	Blood samples were collected at indicated time-points for analysis of hematology parameters like MCV. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Mean Corpuscle Hemoglobin (MCH)	Blood samples were collected at indicated time-points for analysis of hematology parameters like MCH. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Hemoglobin	Blood samples were collected at indicated time-points for analysis of hematology parameters like hemoglobin. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Hematocrit	Blood samples were collected at indicated time-points for analysis of hematology parameters like hematocrit. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Clinical Chemistry Parameter: High Sensitivity C-reactive Protein (hsCRP)	Blood samples were collected at indicated time-points for analysis of clinical parameters like hsCRP. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Clinical Chemistry Parameter of Total Protein and Albumin	Blood samples were collected at indicated time-points for analysis of clinical parameters like total protein and albumin. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Clinical Chemistry Parameters Like Total Bilirubin, Direct Bilirubin and Creatinine	Blood samples were collected at indicated time-points for analysis of clinical parameters like total bilirubin, direct bilirubin and creatinine. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Urine Specific Gravity Analysis by Dipstick Method	Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	SBP and DBP were assessed in a supine position after 5 minutes of rest. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at 2 and 8 hours at Day 1; Days 2, 3, 4 and 5; Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Temperature	Temperature was assessed in a supine position after 5 minutes of rest. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at 2 and 8 hours at Day 1; Days 2, 3, 4 and 5; Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Heart Rate	Heart rate was assessed in a supine position after 5 minutes of rest. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at 2 and 8 hours at Day 1; Days 2, 3, 4 and 5; Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Respiration Rate	Respiration rate was assessed in a supine position after 5 minutes of rest. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at 2 and 8 hours at Day 1; Days 2, 3, 4 and 5; Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Heart Rate: Electrocardiogram (ECG)	12-lead ECG were performed in a supine position using an automated ECG machine that calculated the heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. ECG measurements were performed in triplicate. When multiple ECGs were performed at the same planned timepoint, the average value of each parameter was used. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at 2 and 8 hours on Day 1; Days 2, 3, 4 and 5; Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in PR Interval, QRS Interval, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF) Interval	12-lead ECG were performed in a supine position using an automated ECG machine that calculated PR interval, QRS interval, QT interval and QTcF interval. ECG measurements were performed in triplicate. When multiple ECGs were performed at the same planned timepoint, the average value of each parameter was used. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at 2 and 8 hours on Day 1; Days 2, 3, 4 and 5; Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Clinical Chemistry Parameters Like Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)	Blood samples were collected at indicated time-points for analysis of clinical parameters like ALP, AST and ALT. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Change From Baseline in Clinical Chemistry Parameter Like Glucose, Calcium, Potassium, Sodium, Blood Urea Nitrogen (BUN), and Magnesium	Blood samples were collected at indicated time-points for analysis of clinical parameters like glucose, calcium, potassium, sodium, BUN, and magnesium. Baseline was defined as latest pre-dose assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Number of Participants With Presence of Ketones, Glucose, Occult Blood, and Protein	Urine samples were collected to analyze presence of ketones, occult blood, glucose, and protein in urine. In this dipstick test, the level of occult blood, glucose, ketones and urine protein in urine samples were recorded as negative, trace, 1+ and 2+ indicating proportional concentrations in urine. Only categories with abnormal significant values have been presented.	Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Urine Potential of Hydrogen (pH) Analysis by Dipstick Method	Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).	Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Absolute Values of Complement (C)3 and C4	Blood samples were collected at indicated timepoints for analysis for complement (C3 and C4). Baseline was defined as latest pre-dose assessment with a non-missing value.	Baseline and at Days 2, 3, 4 and 5; Weeks 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf). Pharmacokinetic parameters were calculated by standard non compartmental analysis. Pharmacokinetic Population included participants in the Safety population for whom a pharmcokinetic sample was obtained and analyzed.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
AUC(0-inf) of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf). Pharmacokinetic parameters were calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
AUC(0-inf) of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf). Pharmacokinetic parameters were calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). Pharmacokinetic parameters were calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
AUC(0-t) of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). Pharmacokinetic parameters were calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
AUC(0-t) of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Area Under the Concentration-time Curve From Time Zero to Week 4 (AUC[0-Week 4]) of GSK3511294	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-Week 4). Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, and 4 post-dose
Area Under the Concentration-time Curve From Time Zero to Week 12 (AUC[0-Week 12]) of GSK3511294	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-Week 12). Pharmacokinetic parameters were calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8 and 12 post-dose
Area Under the Concentration-time Curve From Time Zero to Week 26 (AUC [0-Week 26]) of GSK3511294	Blood samples were collected from participants at indicated time points and analyzed for AUC (0-Week 26). Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24 and 26 post-dose
Percentage of AUC (0-inf) Obtained by Extrapolation (%AUCex) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for %AUCex. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
%AUCex of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for %AUCex. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
%AUCex of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for %AUCex. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Maximum Observed Concentration (Cmax) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for Cmax. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
Cmax of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for Cmax. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
Cmax of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for Cmax. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Time of Occurrence of Cmax (Tmax) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for Tmax. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
Tmax of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for Tmax. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
Tmax of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for Tmax. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Time of Last Quantifiable Concentration (Tlast) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for Tlast. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
Tlast of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for Tlast. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
Tlast of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for Tlast. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Apparent Clearance Following Subcutaneous Dosing (CL/F) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for CL/F. CL/F was calculated as dose divided by AUC(0-inf). Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
CL/F of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for CL/F. CL/F was calculated as dose divided by AUC(0-inf). Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
CL/F of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for CL/F. CL/F was calculated as dose divided by AUC(0-inf). Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Apparent Volume of Distribution After Subcutaneous Administration (Vd/F) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for Vd/F. Vd/F was calculated as dose divided by terminal elimination rate constant (lambda_z) *AUC(0-inf). Pharmacokinetic parameters were calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
Vd/F of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for Vd/F. Vd/F was calculated as dose divided by [lambda_z *AUC(0-inf)]. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
Vd/F of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for Vd/F. Vd/F was calculated as dose divided by [lambda_z *AUC(0-inf)]. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Terminal Phase Elimination Rate Constant (Lambda_z) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for lambda_z. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
Lambda_z of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for lambda_z. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
Lambda_z of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for lambda_z. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Terminal Phase Half-life (t1/2) of GSK3511294 2 mg and 10 mg	Blood samples were collected from participants at indicated time points and analyzed for t1/2. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, and 26 post-dose
T1/2 of GSK3511294 30 mg and 100 mg	Blood samples were collected from participants at indicated time points and analyzed for t1/2. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26 and 36 post-dose
T1/2 of GSK3511294 300 mg	Blood samples were collected from participants at indicated time points and analyzed for t1/2. Pharmacokinetic parameters was calculated by standard non compartmental analysis.	Pre-dose, 2 and 8 hours on Day 1; Days 2,3,5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32 and 40 post-dose
Ratio to Baseline in Absolute Blood Eosinophil Count	Blood samples were collected at indicated time-points. Analysis was performed using a mixed model repeated measures analysis (MMRM) model on log-transformed data with fixed categorical effects of treatment, planned timepoint and treatment-by-planned timepoint interaction and fixed continuous covariates of log Baseline blood eosinophil count and log Baseline blood eosinophil count-by-planned timepoint interaction. Baseline is defined as the latest predose non-missing blood eosinophil count. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Pharmacodynamic Population included participants in the 'Safety' population for whom a post-dose pharmacodynamic (ie blood eosinophil) sample was obtained and analyzed.	Baseline, Days 2, 3, 4, 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36, and 40
Number of Participants With Anti-drug Antibody (ADA) Binding to GSK3511294	Serum samples were collected to determine the presence of anti-GSK3511294 binding antibodies using a validated bioanalytical method. Data for any time post-Baseline is reported. The results were categorized as negative, transient positive (defined as a single confirmatory positive immunogenic response that does not occur at the final study assessment) and persistent positive (defined as a confirmatory positive immunogenic response for at least 2 consecutive assessments or a single result at the final study assessment).	Up to Week 40
Titers of Binding ADA to GSK3511294	Serum samples were collected to determine the presence of anti-GSK3511294 binding antibodies using a validated bioanalytical method. Data for any time post-Baseline is reported. Titer was only measured when a positive result was found.	Up to Week 40

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Singh D, Fuhr R, Bird NP, Mole S, Hardes K, Man YL, Cahn A, Yancey SW, Pouliquen IJ. A Phase 1 study of the long-acting anti-IL-5 monoclonal antibody GSK3511294 in patients with asthma. Br J Clin Pharmacol. 2022 Feb;88(2):702-712. doi: 10.1111/bcp.15002. Epub 2021 Aug 24.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2017
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: September 15, 2017
• First Posted (Actual): September 19, 2017

Study Record Updates

• Last Update Posted (Actual): March 1, 2021
• Last Update Submitted That Met QC Criteria: February 5, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: asthma; pharmacokinetics; pharmacodynamics; First time in Human; eosinophils; GSK3511294
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: 205722; 2016-004256-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request Site
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No