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GSK2618960 is a humanized Immunoglobulin G 1 ( IgG1) monoclonal antibody (mAb) that binds to the alpha component (CD127) of the heterodimeric Interleukin-7 receptor (IL-7R). It is being developed for the treatment of autoimmune indications. This study is intended to further explore the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of single ascending doses GSK2618960 in healthy volunteers beyond those already evaluated in I7R116702 (First Time In Human study). The study is anticipated to enrol 18 subjects in total, with 9 subjects in each of the two cohorts.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A GSK2618960 | Experimental | Subjects will receive GSK2618960 0.6 milligram per kilogram (mg/kg) |
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| Cohort A Placebo | Placebo Comparator | Subjects will receive Sodium Chloride Intravenous as placebo |
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| Cohort B GSK2618960 | Experimental | Subjects will receive GSK2618960,planned dose being 2mg/kg. However, actual dose level for Cohort B may be adjusted based on the emerging data on safety, tolerability, PK and RO from Cohort A. The maximum dose will not exceed 2.4 mg/kg (i.e. a 4-fold dose escalation from 0.6 mg/kg) |
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| Cohort B Placebo | Placebo Comparator | Subjects will receive Sodium Chloride Intravenous as placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2618960 | Drug | GSK2618960 will be provided as 100 mg/mL solution for injection to be administered as single dose IV infusion that has to be diluted at the study site with placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Adverse events (AE) | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product | Up to Day 169 |
| Absolute values of vital signs | Vital signs includes systolic and diastolic blood pressure, pulse rate and body temperature. | Up to Day 169 |
| Change from baseline in vital signs | Vital signs includes systolic and diastolic blood pressure, pulse rate and body temperature. | Baseline (Day1) and up to Day 169 |
| Absolute values of Electrocardiogram (ECG) parameters | Single 12-lead ECGs will be obtained. | Up to Day 169 |
| Change from baseline in ECG parameters | Single 12-lead ECGs will be obtained. | Baseline (Day1) and up to Day 169 |
| Absolute values of haematology | Haematology parameters includes Platelet Count, Red blood cells (RBC) Count, White blood cells Count (absolute) (WBC), Haemoglobin and Haematocrit | Up to Day 169 |
| Change from baseline in haematology | Haematology parameters includes Platelet Count, RBC, WBC, Haemoglobin and Haematocrit | Baseline (Day -1) and up to Day 169 |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of PK parameters | PK parameters includes Area Under the Concentration-time curve (AUC) from zero (pre-dose) extrapolated to infinite time (AUC[0-infinite]); AUC from time zero (pre-dose) to last quantifiable concentration within a subject across all treatments (AUC[0-t]); Percentage of AUC(0- infinite) obtained by extrapolation (%AUC-[ex]); Clearance (CL); Volume of distribution (Vss); Maximum observed concentration (Cmax); Time of occurrence of Cmax (Tmax); Terminal half life (t1/2). |
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Inclusion Criteria:
Non-childbearing potential defined as:- pre-menopausal females with a documented tubal ligation or hysterectomy, or post-menopausal defined as 24 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli-international units (MIU) per millilitre (mL) and oestradiol <40 picograms (pg) /mL (< 140 picomole/liter) is confirmatory. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt must discontinue HRT to allow confirmation of postmenopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their postmenopausal status, they can resume use of HRT during the study.]
Exclusion Criteria:
Criteria Based Upon Medical Histories
Criteria Based Upon Diagnostic Assessments
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | CB2 2GG | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30161291 | Derived | Ellis J, van Maurik A, Fortunato L, Gisbert S, Chen K, Schwartz A, McHugh S, Want A, Santos Franco S, Oliveira JJ, Price J, Coles A, Brown K, Su D, Craigen JL, Yang J, Brett S, Davis B, Cheriyan J, Kousin-Ezewu O, Gray F, Thompson PW, Fernando D. Anti-IL-7 receptor alpha monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study. Br J Clin Pharmacol. 2019 Feb;85(2):304-315. doi: 10.1111/bcp.13748. Epub 2018 Dec 3. |
| Label | URL |
|---|---|
| Results for study 200902 can be found on the GSK Clinical Study Register. | View source |
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| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000705473 | GSK2618960 |
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| Placebo | Drug | It is Sodium Chloride Intravenous Infusion |
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| Absolute values of clinical chemistry | Clinical chemistry includes Blood urea nitrogen, Potassium, Aspartate aminotransferase (SGOT), Total and direct bilirubin, Creatinine, Chloride, Alanine aminotransferase (SGPT), Albumin, Glucose, Total Carbon dioxide, Gamma glutamyltransferase, Total Protein, Sodium, Calcium and Alkaline phosphatase | Up to Day 169 |
| Change from baseline in clinical chemistry | Clinical chemistry includes Blood urea nitrogen, Potassium, SGOT, Total and direct bilirubin, Creatinine, Chloride, SGPT, Albumin, Glucose, Total Carbon dioxide, Gamma glutamyltransferase, Total Protein, Sodium, Calcium and Alkaline phosphatase | Baseline (Day -1) and up to Day 169 |
| Absolute values of urinalysis | Urinalysis includes Specific gravity, pH, glucose, protein, blood and ketones by dipstick, Microscopic examination (if blood or protein is abnormal) | Up to Day 169 |
| Change from baseline in urinalysis | Urinalysis includes Specific gravity, pH, glucose, protein, blood and ketones by dipstick, Microscopic examination (if blood or protein is abnormal) | Baseline (Day -1) and up to Day 169 |
| Up to Day 29 |
| Duration of full receptor occupancy (RO) for Cohort A | The extent and duration of receptor occupancy and the inhibition of IL-7 signalling in Stat5 phosphorylation (pSTAT5) will be determined | Up to Day 43 |
| Duration of full RO for Cohort B | The extent and duration of receptor occupancy and the inhibition of IL-7 signalling in pSTAT5 will be determined | Up to Day 57 |
| Relationship between dose/exposure and duration of full RO for Cohort A | The PD/RO relationship of GSK2618960 following single and repeat Intravenous (IV) doses will be determined. | Up to Day 43 |
| Relationship between dose/exposure and duration of full RO for Cohort B | The PD/RO relationship of GSK2618960 following single and repeat IV doses will be determined. | Up to Day 57 |
| Degree of blocking of IL-7R alpha signalling for Cohort A | It will be assessed by residual IL-7- and Thymic Stromal Lymphopoietin (TSLP)-mediated pSTAT5 and Thymus and Activation-Regulated Chemokine (TARC) secretion | Up to Day 43 |
| Degree of blocking of IL-7R alpha signalling for Cohort B | It will be assessed by residual IL-7- and TSLP-mediated pSTAT5 and TARC secretion | Up to Day 57 |
| Incidence of anti-drug antibodies (ADAs) | Blood samples will be collected for the assessment of ADAs in serum using validated electrochemiluminescent (ECL)assays | Up to Day 85 |
| Titre of ADAs | Blood samples will be collected for the assessment of ADAs in serum using validated ECL assays | Up to Day 85 |