Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK2330811 · 2 trials · 1 indication
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as 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, other situations judged by physician. SAEs were collected up to Day 197, but the protocol also allowed investigators to report SAEs occurring after participants had completed the study. This outcome measure includes two SAEs reported after participants had completed the study, occurring on Day 306 and Day 603 following first dose. Safety Population consisted of all randomized participants who have taken at least 1 dose of study treatment.
Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC count. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze the hematology parameters: hemoglobin and MCHC. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze the hematology parameter: MCH. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze the hematology parameters: MCV and MPV. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze the hematology parameters: RBC count and reticulocyte count. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze the hematology parameter: RDW. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze the hematology parameter: Reticulocyte Production Index. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Reticulocyte Production Index (RPI) was calculated as 'Reticulocyte Production Index = Reticulocyte Count (percent \[%\]) multiply by (x) (hematocrit \[%\] divided by \[/\] 45) x 1/ reticulocyte maturation time'.
Blood samples were collected to analyze the hematology parameter: reticulocytes. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected for analysis of clinical chemistry parameters. PCI ranges were low: \<30 grams per liter (g/L) (albumin), high: \>44.2 micromoles per liter (µmol/L) increase from Baseline (creatinine), low: \<3 or high: \>9 mmol/L (glucose), low: \<3 or high: \>5.5 mmol/L (potassium), and low: \<130 or high: \>150 mmol/L (sodium). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there was no change in their category. Participants whose laboratory value category was unchanged (e.g. High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add up to 100%.
Blood samples were collected to analyze chemistry parameter: total protein. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze chemistry parameters: ALP, ALT, AST and LDH. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze chemistry parameters: total bilirubin and direct bilirubin. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze chemistry parameters: cholesterol, direct HDL cholesterol, LDL cholesterol and triglycerides. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from post-dose visit value.
Blood samples were collected to analyze chemistry parameters: corrected calcium and urea. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Blood samples were collected to analyze chemistry parameter: estimated glomerular filtration rate. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Urine samples were collected for the assessment of potential of hydrogen, specific gravity, glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters: potential of hydrogen, specific gravity, glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Only participants with emergent worst case any increase from Baseline values are presented.
Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) were measured in a seated or semi-supine position after 5 minutes of rest using a completely automated device. PCI ranges were: SBP (increase or decrease from Baseline of \>=40 millimeter of mercury \[mmHg\]), DBP (increase or decrease from Baseline of \>=20 mmHg), and HR (increase or decrease from Baseline of \>=30 beats per minute). Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment.
Body temperature was measured in a seated or semi-supine position after 5 minutes of rest. Baseline was defined as the pre-dose Day 1 assessment, unless unavailable, in which case it was the latest pre-dose assessment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings were those which were not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Clinical laboratory tests will include clinical chemistry, hematology and urinalysis.
Vital signs assessment including systolic and diastolic blood pressure, heart rate and body temperature.
ECGs will be measured in the semi-supine position. Triplicate 12-lead ECGs will be recorded at screening, Day 1 pre-dose and Day 5 and single 12-lead ECGs at all other time points.
| Arm | Type | Description |
|---|---|---|
| Cohort 1: GSK2330811 100 mg | EXPERIMENTAL | During Cohort 1, participants will receive a single dose of GSK2330811 100 mg by SC injection via needle and syringe in to the abdomen, thigh or upper arm by the investigator or designee at every other week from D1 to D71 (total 6 doses) for 10 weeks. Participants will be followed-up up to W28 D197. |
| Cohort 2: GSK2330811 300 mg | EXPERIMENTAL | During Cohort 2, participants will receive a single dose of GSK2330811 300 mg by SC injection (3 vials of 1 mL each of GSK2330811 100 mg) via needle and syringe in to the abdomen, thigh or upper arm by the investigator or designee at every other week from D1 to D71 (total 6 doses) for 10 weeks. Participants will be followed-up up to W28 D197. |
| Cohort 1: Placebo | PLACEBO_COMPARATOR | During Cohort 1, participants will receive a single dose of placebo by SC injection via needle and syringe in to the abdomen, thigh or upper arm by the investigator or designee at every other week from D1 to D71 (total 6 doses) for 10 weeks. Participants will be followed-up up to W28 D197. |
| Cohort 2: Placebo | PLACEBO_COMPARATOR | During Cohort 2, participants will receive a single dose of placebo by SC injection (3 vials of 1 mL each) via needle and syringe in to the abdomen, thigh or upper arm by the investigator or designee at every other week from D1 to D71 (total 6 doses) for 10 weeks. Participants will be followed-up up to W28 D197. |
| Cohort 1- GSK2330811(0.1 mg/kg) | EXPERIMENTAL | Subjects will be randomised to receive either 0.1 mg/kg GSK2330811 or placebo s.c single dose in a 3:1 ratio. |
| Cohort 2- GSK2330811(0.3 mg/kg) | EXPERIMENTAL | Subjects will be randomised to receive either 0.3 mg/kg GSK2330811 or placebo s.c single dose in a 3:1 ratio. |
| Cohort 3- GSK2330811(1 mg/kg) | EXPERIMENTAL | Subjects will be randomised to receive either 1 mg/kg GSK2330811 or placebo s.c single dose in a 3:1 ratio. |
| Cohort 4- GSK2330811(3 mg/kg) | EXPERIMENTAL | Subjects will be randomised to receive either 3 mg/kg GSK2330811 or placebo s.c single dose in a 3:1 ratio. |
| Cohort 5- GSK2330811(6 mg/kg) | EXPERIMENTAL | Subjects will be randomised to receive either 6 mg/kg GSK2330811 or placebo s.c single dose in a 3:1 ratio. |
| Name | Type | Description |
|---|---|---|
| GSK2330811 | DRUG | GSK2330811 will be provided in vials and packed in 1 vial per carton. Each vial will contain 1.2 mL fill with 1 mL extractable volume at 100 mg/mL. |
| Placebo | DRUG | Normal saline (0.9 percent weight per volume sodium chloride). |
Inclusion Criteria: * Participants of 18 years or over, at the time of signing the informed consent. * Documented diagnosis of systemic sclerosis with diffuse cutaneous involvement. * Modified rodnan skin score (mRSS) \>=10 and \<=35 at screening. * In all cases, a disease duration of \<=60 months ...
GSK2330811 is an investigational small molecule being studied for the treatment of systemic scleroderma, also called systemic sclerosis. It has been evaluated specifically in diffuse cutaneous systemic sclerosis, a form of the disease in which skin thickening spreads rapidly. It is not an approved therapy and remains in clinical development.
GSK2330811 is being developed by GSK plc, which trades under the ticker GSK. The company sponsored both clinical studies of the compound, including the Phase 2 proof of mechanism trial in diffuse cutaneous systemic sclerosis and an earlier Phase 1 study in healthy volunteers.
GSK2330811 has completed Phase 2 development. Its Phase 2 proof of mechanism study in diffuse cutaneous systemic sclerosis is listed as completed, and an earlier Phase 1 safety and pharmacokinetics study in healthy subjects is also completed. No trials are currently listed as active, and the drug is not approved.
GSK2330811 has been evaluated in two completed trials. NCT03041025 was a Phase 2 proof of mechanism study in diffuse cutaneous systemic sclerosis enrolling 35 participants across the United States, Canada, the Netherlands, and the United Kingdom. NCT02386436 was a Phase 1 safety, tolerability, pharmacokinetics, and pharmacodynamics study in 41 healthy subjects in the United Kingdom.
Yes. The GSK2330811 clinical program used randomized, double-blind, controlled designs. Across the two completed studies, total enrollment was 76 participants, with 35 in the Phase 2 diffuse cutaneous systemic sclerosis trial and 41 healthy volunteers in the Phase 1 study. Participants were adults aged 18 years and older.