AsthmaPhase 1NCT03287310
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 Phase 1 study testing GSK3511294 and Salbutamol/albuterol in people with Asthma, run by GlaxoSmithKline at 5 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- What is being tested?
- GSK3511294 and Salbutamol/albuterol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 17 Oct 2017to 31 Jul 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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 locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United Kingdom3 sites
GSK Investigational Site
Harrow, Middlesex, HA1 3UJ
GSK Investigational Site
London, NW10 7EW
GSK Investigational Site
Manchester, M23 9QZ
Germany2 sites
GSK Investigational Site
Berlin, 14050
GSK Investigational Site
Hanover, Lower Saxony, 30625
About this study
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
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.
- Conditions
- Asthma
- Being tested
- GSK3511294, Placebo, Salbutamol/albuterol
- Keywords
- eosinophils, pharmacokinetics, First time in Human, GSK3511294, pharmacodynamics, asthma
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3511294Drug
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.
PlaceboDrug
Matching Placebo will consist of 0.9% w/v sodium chloride which will be administered by the SC route.
Salbutamol/albuterolDrug
Salbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study.
| Study group | Role | What they receive |
|---|---|---|
| Subjects receiving GSK3511294 in Cohort 1 | Experimental | Six subjects in Cohort 1 will receive a single SC dose of 2 mg GSK3511294. Receives: Drug: GSK3511294; Drug: Salbutamol/albuterol |
| Subjects receiving placebo in Cohort 1 | Placebo comparator | Two subjects in Cohort 1 will receive a single SC dose of placebo. Receives: Drug: Placebo; Drug: Salbutamol/albuterol |
| Subjects receiving GSK3511294 in Cohort 2 | Experimental | Six subjects in Cohort 2 will receive a single SC dose of 10 mg GSK3511294. Receives: Drug: GSK3511294; Drug: Salbutamol/albuterol |
| Subjects receiving placebo in Cohort 2 | Placebo comparator | Two subjects in Cohort 2 will receive a single SC dose of placebo. Receives: Drug: Placebo; Drug: Salbutamol/albuterol |
| Subjects receiving GSK3511294 in Cohort 3 | Experimental | Nine subjects in Cohort 3 will receive a single SC dose of 30 mg GSK3511294. Receives: Drug: GSK3511294; Drug: Salbutamol/albuterol |
| Subjects receiving placebo in Cohort 3 | Placebo comparator | Three subjects in Cohort 3 will receive a single SC dose of placebo. Receives: Drug: Placebo; Drug: Salbutamol/albuterol |
| Subjects receiving GSK3511294 in Cohort 4 | Experimental | Nine subjects in Cohort 4 will receive a single SC dose of 100 mg GSK3511294. Receives: Drug: GSK3511294; Drug: Salbutamol/albuterol |
| Subjects receiving placebo in Cohort 4 | Placebo comparator | Three subjects in Cohort 4 will receive a single SC dose of placebo. Receives: Drug: Placebo; Drug: Salbutamol/albuterol |
| Subjects receiving GSK3511294 in Cohort 5 | Experimental | Six subjects in Cohort 5 will receive a single SC dose of 300 mg GSK3511294. Receives: Drug: GSK3511294; Drug: Salbutamol/albuterol |
| Subjects receiving placebo in Cohort 5 | Placebo comparator | Two subjects in Cohort 5 will receive a single SC dose of placebo. Receives: Drug: Placebo; Drug: Salbutamol/albuterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Baseline and at Days 2, 3, 4 and 5; Weeks 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
Secondary outcomes (36)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Up to Week 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2017
- Study start17 Oct 2017
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a multi-center, double-blind study in which subjects will be allocated to five cohorts. The subjects in each cohort will be randomized to receive GSK3511294 and placebo in a ratio of 3:1. In each cohort, dosing will be staggered: one subject will receive GSK3511294 and one subject will receive placebo at least 72 hours before the remaining subjects in that cohort are dosed. The remaining subjects will be dosed if the review of all safety data up to 72 hours after dosing of the first two subjects in each cohort is satisfactory.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03287310
- Sponsor's protocol ID
- 205722
- Other IDs
- 2016-004256-30, 2016
- Status last verified
- Feb 2021
- First submitted
- 15 Sep 2017
- Last updated
- 1 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request Site
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.
PubMed 34292606
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03287310
- Acronym / sponsor ID
- 205722
- Conditions
- Asthma
- Keywords
- eosinophils, pharmacokinetics, First time in Human, GSK3511294, pharmacodynamics, asthma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 17 Oct 2017 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 19 Sep 2017 (actual)
- Results
- Posted 1 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 10
- Model description
- This is a multi-center, double-blind study in which subjects will be allocated to five cohorts. The subjects in each cohort will be randomized to receive GSK3511294 and placebo in a ratio of 3:1. In each cohort, dosing will be staggered: one subject will receive GSK3511294 and one subject will receive placebo at least 72 hours before the remaining subjects in that cohort are dosed. The remaining subjects will be dosed if the review of all safety data up to 72 hours after dosing of the first two subjects in each cohort is satisfactory.
| Arm | Type | Receives |
|---|---|---|
| Subjects receiving GSK3511294 in Cohort 1 | Experimental | Drug: GSK3511294, Drug: Salbutamol/albuterolSix subjects in Cohort 1 will receive a single SC dose of 2 mg GSK3511294. |
| Subjects receiving placebo in Cohort 1 | Placebo comparator | Drug: Placebo, Drug: Salbutamol/albuterolTwo subjects in Cohort 1 will receive a single SC dose of placebo. |
| Subjects receiving GSK3511294 in Cohort 2 | Experimental | Drug: GSK3511294, Drug: Salbutamol/albuterolSix subjects in Cohort 2 will receive a single SC dose of 10 mg GSK3511294. |
| Subjects receiving placebo in Cohort 2 | Placebo comparator | Drug: Placebo, Drug: Salbutamol/albuterolTwo subjects in Cohort 2 will receive a single SC dose of placebo. |
| Subjects receiving GSK3511294 in Cohort 3 | Experimental | Drug: GSK3511294, Drug: Salbutamol/albuterolNine subjects in Cohort 3 will receive a single SC dose of 30 mg GSK3511294. |
| Subjects receiving placebo in Cohort 3 | Placebo comparator | Drug: Placebo, Drug: Salbutamol/albuterolThree subjects in Cohort 3 will receive a single SC dose of placebo. |
| Subjects receiving GSK3511294 in Cohort 4 | Experimental | Drug: GSK3511294, Drug: Salbutamol/albuterolNine subjects in Cohort 4 will receive a single SC dose of 100 mg GSK3511294. |
| Subjects receiving placebo in Cohort 4 | Placebo comparator | Drug: Placebo, Drug: Salbutamol/albuterolThree subjects in Cohort 4 will receive a single SC dose of placebo. |
| Subjects receiving GSK3511294 in Cohort 5 | Experimental | Drug: GSK3511294, Drug: Salbutamol/albuterolSix subjects in Cohort 5 will receive a single SC dose of 300 mg GSK3511294. |
| Subjects receiving placebo in Cohort 5 | Placebo comparator | Drug: Placebo, Drug: Salbutamol/albuterolTwo subjects in Cohort 5 will receive a single SC dose of placebo. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (33 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK3511294GSK3511294 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 | Subjects receiving GSK3511294 in Cohort 1, Subjects receiving GSK3511294 in Cohort 2, Subjects receiving GSK3511294 in Cohort 3, Subjects receiving GSK3511294 in Cohort 4, Subjects receiving GSK3511294 in Cohort 5 |
| PlaceboMatching Placebo will consist of 0.9% w/v sodium chloride which will be administered by the SC route. | Drug | Subjects receiving placebo in Cohort 1, Subjects receiving placebo in Cohort 2, Subjects receiving placebo in Cohort 3, Subjects receiving placebo in Cohort 4, Subjects receiving placebo in Cohort 5 |
| Salbutamol/albuterolSalbutamol/albuterol will be supplied to all subjects for use as rescue medication during the study. | Drug | Subjects receiving GSK3511294 in Cohort 1, Subjects receiving GSK3511294 in Cohort 2, Subjects receiving GSK3511294 in Cohort 3, Subjects receiving GSK3511294 in Cohort 4, Subjects receiving GSK3511294 in Cohort 5, Subjects receiving placebo in Cohort 1, Subjects receiving placebo in Cohort 2, Subjects receiving placebo in Cohort 3, Subjects receiving placebo in Cohort 4, Subjects receiving placebo in Cohort 5 |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious AEs (SAE)
Time frame: Up to Week 40
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.
Number of Participants With Adverse Events of Special Interest (AESI)
Time frame: Up to Week 40
AESIs were defined as Hypersensitivity (narrow) and Injection site reactions like hematoma and swelling.
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Red Blood Cell Count (RBC)
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Mean Corpuscle Volume (MCV)
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Mean Corpuscle Hemoglobin (MCH)
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Hemoglobin
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Hematocrit
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Clinical Chemistry Parameter: High Sensitivity C-reactive Protein (hsCRP)
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Clinical Chemistry Parameter of Total Protein and Albumin
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Clinical Chemistry Parameters Like Total Bilirubin, Direct Bilirubin and Creatinine
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Urine Specific Gravity Analysis by Dipstick Method
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: 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
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.
Change From Baseline in Temperature
Time frame: 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
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.
Change From Baseline in Heart Rate
Time frame: 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
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.
Change From Baseline in Respiration Rate
Time frame: 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
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.
Change From Baseline in Heart Rate: Electrocardiogram (ECG)
Time frame: 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
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.
Change From Baseline in PR Interval, QRS Interval, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF) Interval
Time frame: 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
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.
Change From Baseline in Clinical Chemistry Parameters Like Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Change From Baseline in Clinical Chemistry Parameter Like Glucose, Calcium, Potassium, Sodium, Blood Urea Nitrogen (BUN), and Magnesium
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Number of Participants With Presence of Ketones, Glucose, Occult Blood, and Protein
Time frame: Baseline and at Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
Urine Potential of Hydrogen (pH) Analysis by Dipstick Method
Time frame: Days 2, 3, 4 and 5, Weeks 1, 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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).
Absolute Values of Complement (C)3 and C4
Time frame: Baseline and at Days 2, 3, 4 and 5; Weeks 2, 4, 8, 12, 18, 24, 26, 32, 36 and 40
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.
36 secondary outcomes
Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK3511294 2 mg and 10 mg
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to Week 40
Titers of Binding ADA to GSK3511294
Time frame: Up to Week 40
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34292606Singh 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.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request Site
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK3511294 and Salbutamol/albuterol in people with Asthma, run by GlaxoSmithKline at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) and Serious AEs (SAE) (time frame: Up to Week 40). The study lists 23 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03287310, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2021.