Asthma
Conditions
Keywords
Single dose study, Immunogenicity, GSK3511294, Chinese healthy participants
Brief summary
This single dose pharmacokinetic (PK) study aims to investigate the PK, safety, tolerability and immunogenicity of two dose levels of GSK3511294 administered subcutaneously in Chinese healthy participants
Interventions
BIOLOGICALDepemokimab
Depemokimab was administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant between 18 to 45 years of age. * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, electrocardiograms and vital signs. * Body weight greater than or equal to (\>=)50.0 kilograms (kg) for males, \>=45.0 kg for females, and body mass index (BMI) within the range (19.0-26.0) kg/meter square (m\^2) (inclusive). * Contraceptive use by men and/or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Capable of giving signed informed consent.
Exclusion criteria
* Participant is pregnant, breastfeeding, or a woman of childbearing potential * History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs * Participants with allergy/intolerance to a monoclonal antibody or biologic or participants with a previous history of clinically significant multiple or severe allergic reactions/intolerance * Current evidence or recent history of an infective illness * A positive pre-study drug/alcohol screen or a history (or suspected history) of alcohol misuse or substance abuse * Clinically significant abnormalities * Participants with Coronavirus Disease-2019 (COVID-19) * With prior/concurrent clinical study experience.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero (Pre-Dose) Extrapolated to Infinite Time (AUC[0-Infinity]) of Depemokimab | Day 1 (Pre-dose, 2h, and 8h Post-dose), Day 2, Day 3, Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, and Day 183 | Blood samples were collected from participants at indicated time points and analyzed for AUC(0-Infinity). Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| AUC From Time 0 (Pre-Dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments (AUC[0-T]) of Depemokimab | Day 1 (Pre-dose, 2h, and 8h Post-dose), Day 2, Day 3, Day 5, Day 8, Day 15, Day 29, Day 57, Day 85, Day 127, Day 169, and Day 183 | 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. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| AUC From Time 0 (Pre-dose) to Week 4 (AUC[0-Week 4]) of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, and 29 | Blood samples were collected from participants at indicated time points and analyzed for AUC(0-Week 4). Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 4 post-dose correlates to Day 1 plus 28 days, that is, Day 29. |
| AUC From Time 0 (Pre-dose) To Week 12 (AUC[0-Week 12]) Of Depemokimab | Pre-dose (Day 1); 2 h, 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, and 85 | 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. As the first dose of depemokimab was administered on Day 1, Week 12 post-dose correlates to Day 1 plus 84 days, that is, Day 85. |
| AUC From Time 0 (Pre-dose) To Week 26 [AUC(0-Week 26)] of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for AUC(0-Week 26). Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| Percentage Of AUC(0-Infinity) Obtained by Extrapolation (%AUCex) of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for percentage of AUC(0-Infinity) obtained by extrapolation. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| Maximum Observed Plasma Concentration (Cmax) of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for Cmax. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| Time of Occurrence of Cmax (Tmax) Of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for Tmax. Pharmacokinetic parameters were calculated by standard non compartmental analysis. Tmax was determined directly from the plasma concentration-time data. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| Time To Last Quantifiable Concentration (Tlast) of Depemokimab | Pre-dose (day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for Tlast. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| Apparent Clearance (CL/F) of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for Apparent Clearance. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| Apparent Volume of Distribution (Vz/F) of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for apparent volume of distribution. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| Terminal Elimination Rate Constant (Lambda Z) of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for Terminal elimination rate constant. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
| Terminal Phase Half-Life (T1/2) of Depemokimab | Pre-dose (Day 1); 2 hours (h), 8 h, 24 h, and 48 h post-dose; Days 5, 8, 15, 29, 57, 85, 127, 169, and 183 | Blood samples were collected from participants at indicated time points and analyzed for Terminal phase half-life. Pharmacokinetic parameters were calculated by standard non compartmental analysis. As the first dose of depemokimab was administered on Day 1, Week 26 post-dose correlates to Day 1 plus 182 days, that is, Day 183. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AE) And Serious Adverse Events (SAEs) | From the start of the study intervention (Day 1) up to Day 211 (End of follow-up) | 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 any untoward medical occurrence that 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 in the offspring of a study participant, or is considered or defined as an important medical event. |
| Change From Baseline in Hematology Parameter: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes | Baseline (Day -1), Days 2, 3, 5, Weeks 1, 2, 4, 8, 12, 18, 24 and Week 26 | Blood samples were collected for the assessment of hematology parameters including (WBC) count with differential that is, Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. 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 Hematology Parameter: Hemoglobin | Baseline (Day -1), Days 2, 3, 5, Weeks 1, 2, 4, 8, 12, 18, 24 and 26 | Blood samples were collected for the assessment of change from baseline in hematology parameters including 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 Hematology Parameter: Hematocrit | Baseline (Day -1), Days 2, 3, 5, Weeks 1, 2, 4, 8, 12, 18, 24 and 26 | Blood samples were collected for the assessment of change from baseline in hematology parameters including 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 Hematology Parameter: Mean Corpuscular Volume (MCV) | Baseline (Day -1), Days 2, 3, 5, Weeks 1, 2, 4, 8, 12, 18, 24 and 26 | Blood samples were collected for the assessment of change from baseline in hematology parameters including mean corpuscular volume. 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 Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) | Baseline (Day -1), Days 2, 3, 5, Weeks 1, 2, 4, 8, 12, 18, 24 and 26 | Blood samples were collected for the assessment of change from baseline in hematology parameters including mean Corpuscular 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 Hematology Parameter: Reticulocytes | Baseline (Day -1), Days 2, 3, 5, Weeks 1, 2, 4, 8, 12, 18, 24 and Week 26 | Blood samples were collected for the assessment of change from baseline in hematology parameters including Reticulocytes. 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 Hematology Parameter: Erythrocytes | Baseline (Day -1), Days 2, 3, 5, Weeks 1, 2, 4, 8, 12, 18, 24 and Week 26 | Change from baseline in hematology parameter including Erythrocytes. 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: Sodium, Potassium, Calcium, Glucose And Urea | Baseline (Pre-dose on Day -1), Week 1, 4, 8, 12, 24 and Week 26 | Blood samples was collected for the assessment of clinical chemistry parameters including Sodium, potassium, calcium, glucose, and urea. 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: Direct Bilirubin, Bilirubin, and Creatinine | Baseline (Day -1), Week 1, 4, 8, 12, 24 and Week 26 | Blood samples was collected for the assessment of clinical chemistry parameters including direct bilirubin, bilirubin, and creatinine\[MB10.1\]. 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: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) | Baseline (Day -1), Week 1, 4, 8, 12, 24 and Week 26 | Blood samples was collected for the assessment of clinical chemistry parameters including AST, ALT, ALP, and GGT. 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 Albumin and Total Protein | Baseline (Day -1), Week 1, 4, 8, 12, 24 and Week 26 | Blood samples was collected for the assessment of clinical chemistry parameters including Albumin. and Total Protein. 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. |
| Absolute Values of Complement C3 And C4 at Each Timepoint | Baseline (Day -1), Week 1, 4, 8, 12, 24 and Week 26 | 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. |
| Ratio to Baseline at Each Timepoint of Complement C3 And C4 | Baseline (Day -1), Week 1, 4, 8, 12, 24 and Week 26 | 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. |
| Change From Baseline in Systolic and Diastolic Blood Pressure | Baseline (Day -1), Day 1 (2 hours), Day 1 (8 hours), Days 2, 3, 5, Weeks 1, 2, 4, 8, 12, 18, 24 and 26 | Systolic blood pressure (sBP) is a measure of blood pressure while the heart is beating. Diastolic blood pressure (dBP) is a measure of blood pressure while the heart is relaxed. 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 Body Temperature | Baseline (Day -1), Day 1 (2 hours), Day 1 (8 hours), Day 2, 3, 5, Week 1, 2, 4, 8, 12, 18, 24 and 26 | Body temperature was measured in participants in resting state. 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 Pulse Rate | Baseline (Day -1), Day 1 (2 hour), Day 1 (8 hour), Day 2, 3, 5, Week 1, 4, 8, 12, 18, 24 and Week 26 | The vital signs followed in this analysis was pulse rate, expressed as beats per minute (bpm). 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 ECG Parameters: PR Interval, Aggregate, QRS Duration, Aggregate, QT Interval, Aggregate, QTcF Interval, Aggregate | Baseline (Day -1), Day 1 (2 hour), Day 1 (8 hour), Day 2, 3, 5, Week 1, 4, 8, 12, 18, 24 and Week 26 | 12-lead ECG were performed in a supine position using an automated ECG machine that calculated the heart rate and measured PR interval, QRS duration, QT interval and corrected QT using Fridericia's Formula (QTc\[MB13.1\]F) intervals. ECG measurements were performed in triplicate. When multiple ECGs were performed at the same planned timepoint, the aggregate \[MB14.1\]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. |
| Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Depemokimab | Day 1 (Pre-dose), Week 4, Week 12, and Week 26 | Serum samples were collected to determine the presence of anti-depemokimab binding antibodies using a validated bioanalytical method. Data is reported by visit. The results were categorized as negative and positive. A participant is considered positive if they have at least one positive post-Baseline ADA result. Number of participants with positive ADAs against depemokimab was reported in this outcome measure. |
| Titres of Binding ADA's to Depemokimab | Up to Week 26 | Serum samples were collected to determine the presence of anti-depemokimab binding antibodies using a validated bioanalytical method. Data is reported by visit. Titer was only measured when a positive result was found. |
Countries
China
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Pre-assignment details
A total of 20 participants were enrolled and randomized in 1:1 ratio in each arm to receive either depemokimab 100 milligrams (mg) or 300 mg.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 29.7 Years STANDARD_DEVIATION 6.41 |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 10 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 10 / 10 | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
None listed