Asthma, Healthy Volunteers
Conditions
Keywords
Pharmacokinetics, Pharmacodynamics, Safety, GSK3772847, Tolerability
Brief summary
GSK3772847, an anti-interleukin (IL) 33-receptor monoclonal antibody, is a novel treatment for asthma. The purpose of this study to evaluate the safety and tolerability, PK and PD of single ascending doses of GSK3772847 administered subcutaneously (SC) to healthy participants. This study will also establish the bioavailability of SC formulation and evaluate the safety in particular injection site tolerability of route. Participants will either receive a single dose of 70 milligram (mg) GSK3772847 or placebo in (Cohort 1) and 140 mg GSK3772847 or placebo in Cohorts 2, 3 (Japanese participants) and 4 (Chinese participants). The site of injection will be upper arm; abdomen or thigh for cohorts 1 and 2 with cohorts 3 and 4 will receive injections in the upper arm only. Approximately, the total duration of study will be up to 89 days.
Interventions
BIOLOGICALmelrilimab (GSK3772847) 70 milligram (mg)
melrilimab (GSK3772837) will be available at a dose strength of 70 milligram per milliliter (mg/mL) in a 3 milliliter (mL) glass vial.
BIOLOGICALmelrilimab (GSK3772847) 140 milligram (mg)
Two doses of melrilimab (GSK3772837) 70 milligram per milliliter (mg/mL) will be administered to achieve a dose strength of 140 milligram per milliliter (mg/mL)
OTHERPlacebo
Placebo to match melrilimab (GSK3772847) will be available in the form of solution for injection in a 3 milliliter (mL) glass vial.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double blind study and participants and investigator will be masked.
Intervention model description
This is a single arm study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants age in between 18 to 65 years, at the time of signing the informed consent. * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameters not specifically listed in the
Exclusion criteria
that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor (if required), agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or results. * Japanese participants are eligible based on meeting all of the following criteria: healthy male and female participants born in Japan; are descendants of four ethnic Japanese grandparents and two ethnic Japanese parents; holding a Japanese passport or identity papers; being able to speak Japanese; have lived outside Japan for less than 10 years at the time of screening. * Chinese Participants are eligible based on meeting all of the following: healthy male and female participants born in mainland China; are descendants of four Chinese grandparents and two Chinese parents; holding a Chinese passport or identity papers; being able to speak Chinese; have lived outside China for less than 10 years at the time of screening; Body weight 35-150 kilogram (kg) and body mass index (BMI) within the range 18-32 kilogram per square meter (kg/m2) (inclusive). * Female participant: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies; is not a woman of childbearing potential (WOCBP) or is a WOCBP and using an acceptable contraceptive method during the intervention period (at a minimum until after the last dose of study intervention); the investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention; a WOCBP must have a negative highly sensitive pregnancy test (\[urine\] as required by local regulations) within 24 hours before the first dose of study intervention; if a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required,. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive; additional requirements for pregnancy testing during and after study intervention are located; The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. * Contraceptive use by men 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 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Terminal Half-life (t1/2) of GSK3772847 | Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847. |
| Area Under the Plasma Concentration Time Curve From 0 to t (AUC[0-t]) of GSK3772847 | Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847. Pharmacokinetic Population consisted of all randomized participants who received at least one dose of study treatment, and for whom at least one pharmacokinetic sample was obtained, analyzed and measurable. |
| Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3772847 | Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847. |
| Maximum Observed Plasma Concentration (Cmax) of GSK3772847 | Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847. |
| Time to Cmax (Tmax) of GSK3772847 | Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85 | Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 85 | 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. A 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 or significant disability/incapacity, is a congenital anomaly/birth defect, and other situations which involve medical or scientific judgment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration | Baseline and up to Day 85/early withdrawal | Blood samples were collected to measure total soluble ST2 concentration. Maximal increase from Baseline was the largest increase calculated across all timepoints post dose. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline was the most recent recorded value before dosing on Day 1 (Pre-dose). |
| Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Days 1, 15, 29, 57 and 85/early withdrawal | Serum samples were collected at indicated time points and analyzed for the presence of anti-GSK3772847 antibodies using a tiered approach including a screening assay, a confirmation assay and calculation of titer. |
| Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Baseline, Days 5, 15, 29 and 85/early withdrawal | Blood samples were collected at indicated time points to measure 4BetaOH cholesterol/cholesterol. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline value was the latest pre-dose assessment (Day 1 Pre-dose). |
| Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration | Baseline and up to Day 85/early withdrawal | Blood samples were collected to measure free soluble ST2 concentration. Maximal decrease from Baseline was the largest decrease calculated across all time points post dose. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline was the most recent recorded value before dosing on Day 1 (Pre-dose). Pharmacodynamic Population consisted of all randomized participants who received at least one dose of study treatment, and for whom at least one pharmacokinetic sample was obtained, analyzed and measurable. |
Countries
United States
Participant flow
Recruitment details
Participants who met the eligibility criteria were assigned to one of the four cohorts and were randomly allocated within each cohort to receive a single dose of either GSK3772847 or placebo. All treatments were administered subcutaneously. The site of injection was randomized to the upper arm, abdomen, or thigh for cohorts 1 and 2. Injection was given in the upper arm only in cohorts 3 and 4.
Pre-assignment details
A total of 65 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohorts 1 and 2: Placebo SC Participants received a single dose of placebo subcutaneous (SC) injection in the upper arm, abdomen or thigh by a health care professional in Cohorts 1 and 2. | 13 |
| Cohort 1: GSK3772847 70 mg SC Participants received a single dose of GSK3772847 70 milligram (mg) SC injection in the upper arm, abdomen or thigh by a health care professional in Cohort 1. | 18 |
| Cohort 2: GSK3772847 140 mg SC Participants received a single dose of GSK3772847 140 mg SC injection in the upper arm, abdomen or thigh by a health care professional in Cohort 2. | 18 |
| Cohorts 3 and 4: Placebo SC Japanese and Chinese participants received a single dose of placebo SC injection in the upper arm by a health care professional in Cohorts 3 and 4. | 4 |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants Japanese participants received a single dose of GSK3772847 140 mg SC injection in the upper arm by a health care professional in Cohort 3. | 6 |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants Chinese participants received a single dose of GSK3772847 140 mg SC injection in the upper arm by a health care professional in Cohort 4. | 6 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohorts 1 and 2: Placebo SC | Cohort 1: GSK3772847 70 mg SC | Cohort 2: GSK3772847 140 mg SC | Cohorts 3 and 4: Placebo SC | Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized 18-64 years | 13 Participants | 18 Participants | 18 Participants | 4 Participants | 6 Participants | 6 Participants | 65 Participants |
| Age, Customized >=65-84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian: Central/South Asian Heritage | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian: East Asian Heritage | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 6 Participants | 8 Participants |
| Race/Ethnicity, Customized Asian: Japanese Heritage | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants | 0 Participants | 8 Participants |
| Race/Ethnicity, Customized Asian: South East Asian Heritage | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 11 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White: White/Caucasian/European Heritage | 8 Participants | 13 Participants | 14 Participants | 0 Participants | 0 Participants | 0 Participants | 35 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 9 Participants | 4 Participants | 5 Participants | 1 Participants | 33 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 9 Participants | 0 Participants | 1 Participants | 5 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 18 | 0 / 18 | 0 / 4 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 13 | 2 / 18 | 3 / 18 | 1 / 4 | 2 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 13 | 0 / 18 | 0 / 18 | 0 / 4 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Apparent Terminal Half-life (t1/2) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1 and 2: Placebo SC | Apparent Terminal Half-life (t1/2) of GSK3772847 | 243.275 Hours | Geometric Coefficient of Variation 17.1 |
| Cohort 1: GSK3772847 70 mg SC | Apparent Terminal Half-life (t1/2) of GSK3772847 | 293.144 Hours | Geometric Coefficient of Variation 27.6 |
| Cohort 2: GSK3772847 140 mg SC | Apparent Terminal Half-life (t1/2) of GSK3772847 | 342.622 Hours | Geometric Coefficient of Variation 36.8 |
| Cohorts 3 and 4: Placebo SC | Apparent Terminal Half-life (t1/2) of GSK3772847 | 291.690 Hours | Geometric Coefficient of Variation 22.2 |
Primary
Area Under the Plasma Concentration Time Curve From 0 to t (AUC[0-t]) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847. Pharmacokinetic Population consisted of all randomized participants who received at least one dose of study treatment, and for whom at least one pharmacokinetic sample was obtained, analyzed and measurable.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1 and 2: Placebo SC | Area Under the Plasma Concentration Time Curve From 0 to t (AUC[0-t]) of GSK3772847 | 4139.092 Hours*microgram per milliliter | Geometric Coefficient of Variation 34.1 |
| Cohort 1: GSK3772847 70 mg SC | Area Under the Plasma Concentration Time Curve From 0 to t (AUC[0-t]) of GSK3772847 | 10271.279 Hours*microgram per milliliter | Geometric Coefficient of Variation 25.2 |
| Cohort 2: GSK3772847 140 mg SC | Area Under the Plasma Concentration Time Curve From 0 to t (AUC[0-t]) of GSK3772847 | 13356.462 Hours*microgram per milliliter | Geometric Coefficient of Variation 29.7 |
| Cohorts 3 and 4: Placebo SC | Area Under the Plasma Concentration Time Curve From 0 to t (AUC[0-t]) of GSK3772847 | 11285.792 Hours*microgram per milliliter | Geometric Coefficient of Variation 25.4 |
Primary
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1 and 2: Placebo SC | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3772847 | 4336.865 Hours*microgram per milliliter | Geometric Coefficient of Variation 32.9 |
| Cohort 1: GSK3772847 70 mg SC | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3772847 | 10575.235 Hours*microgram per milliliter | Geometric Coefficient of Variation 25.2 |
| Cohort 2: GSK3772847 140 mg SC | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3772847 | 13936.982 Hours*microgram per milliliter | Geometric Coefficient of Variation 34 |
| Cohorts 3 and 4: Placebo SC | Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3772847 | 11576.445 Hours*microgram per milliliter | Geometric Coefficient of Variation 26.6 |
Primary
Maximum Observed Plasma Concentration (Cmax) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1 and 2: Placebo SC | Maximum Observed Plasma Concentration (Cmax) of GSK3772847 | 7.8276 Microgram per milliliter | Geometric Coefficient of Variation 38.4 |
| Cohort 1: GSK3772847 70 mg SC | Maximum Observed Plasma Concentration (Cmax) of GSK3772847 | 15.0569 Microgram per milliliter | Geometric Coefficient of Variation 24.5 |
| Cohort 2: GSK3772847 140 mg SC | Maximum Observed Plasma Concentration (Cmax) of GSK3772847 | 15.9309 Microgram per milliliter | Geometric Coefficient of Variation 25.5 |
| Cohorts 3 and 4: Placebo SC | Maximum Observed Plasma Concentration (Cmax) of GSK3772847 | 15.8324 Microgram per milliliter | Geometric Coefficient of Variation 15.2 |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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. A 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 or significant disability/incapacity, is a congenital anomaly/birth defect, and other situations which involve medical or scientific judgment.
Time frame: Up to Day 85
Population: Safety Population consisted of all randomized participants who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohorts 1 and 2: Placebo SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| Cohorts 1 and 2: Placebo SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 1: GSK3772847 70 mg SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 1: GSK3772847 70 mg SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Cohort 2: GSK3772847 140 mg SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 2: GSK3772847 140 mg SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| Cohorts 3 and 4: Placebo SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 Participants |
| Cohorts 3 and 4: Placebo SC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
Primary
Time to Cmax (Tmax) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Population: Pharmacokinetic Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohorts 1 and 2: Placebo SC | Time to Cmax (Tmax) of GSK3772847 | 120.000 Hours |
| Cohort 1: GSK3772847 70 mg SC | Time to Cmax (Tmax) of GSK3772847 | 130.358 Hours |
| Cohort 2: GSK3772847 140 mg SC | Time to Cmax (Tmax) of GSK3772847 | 146.175 Hours |
| Cohorts 3 and 4: Placebo SC | Time to Cmax (Tmax) of GSK3772847 | 204.925 Hours |
Secondary
Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration
Blood samples were collected to measure free soluble ST2 concentration. Maximal decrease from Baseline was the largest decrease calculated across all time points post dose. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline was the most recent recorded value before dosing on Day 1 (Pre-dose). Pharmacodynamic Population consisted of all randomized participants who received at least one dose of study treatment, and for whom at least one pharmacokinetic sample was obtained, analyzed and measurable.
Time frame: Baseline and up to Day 85/early withdrawal
Population: Pharmacodynamic Population. Only those participants with data available at indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohorts 1 and 2: Placebo SC | Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration | 0.7573 Ratio |
| Cohort 1: GSK3772847 70 mg SC | Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration | 0.0621 Ratio |
| Cohort 2: GSK3772847 140 mg SC | Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration | 0.0417 Ratio |
| Cohorts 3 and 4: Placebo SC | Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration | 0.8073 Ratio |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration | 0.0453 Ratio |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration | 0.0433 Ratio |
Secondary
Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration
Blood samples were collected to measure total soluble ST2 concentration. Maximal increase from Baseline was the largest increase calculated across all timepoints post dose. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline was the most recent recorded value before dosing on Day 1 (Pre-dose).
Time frame: Baseline and up to Day 85/early withdrawal
Population: Pharmacodynamic Population. Only those participants with data available at indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohorts 1 and 2: Placebo SC | Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration | 2.0573 Ratio |
| Cohort 1: GSK3772847 70 mg SC | Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration | 25.4604 Ratio |
| Cohort 2: GSK3772847 140 mg SC | Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration | 40.6790 Ratio |
| Cohorts 3 and 4: Placebo SC | Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration | 1.7203 Ratio |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration | 39.1039 Ratio |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration | 45.7791 Ratio |
Secondary
Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies
Serum samples were collected at indicated time points and analyzed for the presence of anti-GSK3772847 antibodies using a tiered approach including a screening assay, a confirmation assay and calculation of titer.
Time frame: Days 1, 15, 29, 57 and 85/early withdrawal
Population: Pharmacodynamic Population. Only those participants with data available at indicated time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohorts 1 and 2: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 57: n=12,18,18,4,6,6 | 0 Participants |
| Cohorts 1 and 2: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 1: n=13,18,18,4,6,6 | 0 Participants |
| Cohorts 1 and 2: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 85/early withdrawal: n=12,18,18,4,6,6 | 0 Participants |
| Cohorts 1 and 2: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 29: n=12,18,17,4,6,6 | 0 Participants |
| Cohorts 1 and 2: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 15: n=13,18,18,4,6,6 | 0 Participants |
| Cohort 1: GSK3772847 70 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 15: n=13,18,18,4,6,6 | 0 Participants |
| Cohort 1: GSK3772847 70 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 1: n=13,18,18,4,6,6 | 0 Participants |
| Cohort 1: GSK3772847 70 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 57: n=12,18,18,4,6,6 | 0 Participants |
| Cohort 1: GSK3772847 70 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 29: n=12,18,17,4,6,6 | 0 Participants |
| Cohort 1: GSK3772847 70 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 85/early withdrawal: n=12,18,18,4,6,6 | 0 Participants |
| Cohort 2: GSK3772847 140 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 85/early withdrawal: n=12,18,18,4,6,6 | 0 Participants |
| Cohort 2: GSK3772847 140 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 29: n=12,18,17,4,6,6 | 0 Participants |
| Cohort 2: GSK3772847 140 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 57: n=12,18,18,4,6,6 | 0 Participants |
| Cohort 2: GSK3772847 140 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 15: n=13,18,18,4,6,6 | 0 Participants |
| Cohort 2: GSK3772847 140 mg SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 1: n=13,18,18,4,6,6 | 0 Participants |
| Cohorts 3 and 4: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 85/early withdrawal: n=12,18,18,4,6,6 | 0 Participants |
| Cohorts 3 and 4: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 1: n=13,18,18,4,6,6 | 0 Participants |
| Cohorts 3 and 4: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 15: n=13,18,18,4,6,6 | 0 Participants |
| Cohorts 3 and 4: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 29: n=12,18,17,4,6,6 | 0 Participants |
| Cohorts 3 and 4: Placebo SC | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 57: n=12,18,18,4,6,6 | 0 Participants |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 29: n=12,18,17,4,6,6 | 0 Participants |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 57: n=12,18,18,4,6,6 | 0 Participants |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 85/early withdrawal: n=12,18,18,4,6,6 | 0 Participants |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 1: n=13,18,18,4,6,6 | 0 Participants |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 15: n=13,18,18,4,6,6 | 0 Participants |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 85/early withdrawal: n=12,18,18,4,6,6 | 1 Participants |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 1: n=13,18,18,4,6,6 | 0 Participants |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 29: n=12,18,17,4,6,6 | 0 Participants |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 15: n=13,18,18,4,6,6 | 0 Participants |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies | Day 57: n=12,18,18,4,6,6 | 1 Participants |
Secondary
Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol
Blood samples were collected at indicated time points to measure 4BetaOH cholesterol/cholesterol. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline value was the latest pre-dose assessment (Day 1 Pre-dose).
Time frame: Baseline, Days 5, 15, 29 and 85/early withdrawal
Population: Pharmacodynamic Population. Only those participants with data available at indicated time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohorts 1 and 2: Placebo SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 29: n=12,18,17,4,6,6 | 1.119 Ratio |
| Cohorts 1 and 2: Placebo SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 15: n=11,18,18,4,6,6 | 1.021 Ratio |
| Cohorts 1 and 2: Placebo SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 5: n=13,18,18,4,6,6 | 1.117 Ratio |
| Cohorts 1 and 2: Placebo SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 85/Early withdrawal: n=12,18,18,4,6,6 | 0.923 Ratio |
| Cohort 1: GSK3772847 70 mg SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 85/Early withdrawal: n=12,18,18,4,6,6 | 1.032 Ratio |
| Cohort 1: GSK3772847 70 mg SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 5: n=13,18,18,4,6,6 | 0.998 Ratio |
| Cohort 1: GSK3772847 70 mg SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 15: n=11,18,18,4,6,6 | 0.992 Ratio |
| Cohort 1: GSK3772847 70 mg SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 29: n=12,18,17,4,6,6 | 0.980 Ratio |
| Cohort 2: GSK3772847 140 mg SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 85/Early withdrawal: n=12,18,18,4,6,6 | 0.901 Ratio |
| Cohort 2: GSK3772847 140 mg SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 29: n=12,18,17,4,6,6 | 1.200 Ratio |
| Cohort 2: GSK3772847 140 mg SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 15: n=11,18,18,4,6,6 | 1.092 Ratio |
| Cohort 2: GSK3772847 140 mg SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 5: n=13,18,18,4,6,6 | 1.092 Ratio |
| Cohorts 3 and 4: Placebo SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 29: n=12,18,17,4,6,6 | 1.143 Ratio |
| Cohorts 3 and 4: Placebo SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 15: n=11,18,18,4,6,6 | 1.106 Ratio |
| Cohorts 3 and 4: Placebo SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 85/Early withdrawal: n=12,18,18,4,6,6 | 0.930 Ratio |
| Cohorts 3 and 4: Placebo SC | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 5: n=13,18,18,4,6,6 | 1.062 Ratio |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 29: n=12,18,17,4,6,6 | 1.041 Ratio |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 85/Early withdrawal: n=12,18,18,4,6,6 | 0.826 Ratio |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 5: n=13,18,18,4,6,6 | 1.051 Ratio |
| Cohort 3: GSK3772847 140 mg SC in Japanese Participants | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 15: n=11,18,18,4,6,6 | 1.054 Ratio |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 15: n=11,18,18,4,6,6 | 1.285 Ratio |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 85/Early withdrawal: n=12,18,18,4,6,6 | 0.946 Ratio |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 5: n=13,18,18,4,6,6 | 1.192 Ratio |
| Cohort 4: GSK3772847 140 mg SC in Chinese Participants | Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol | Day 29: n=12,18,17,4,6,6 | 1.488 Ratio |