Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01777243 | A Study to Evaluate the Safety of GSK2398852 When Co-administered With GSK2315698 in Patients With Systemic Amyloidosis | PHASE1 | COMPLETED | 25 | — | — | May 13, 2013 | Dec 22, 2015 | Jul 24, 2018 | 2 | United Kingdom |
Adverse events (AEs) will be collected from the start of Study Treatment and until the follow-up contact.
Safety data will include assessments of clinical laboratory tests (hematology, clinical chemistry and urinalysis).
Safety data will include measurements of vital signs (semi supine systolic and diastolic blood pressure, pulse rate and temperature measured orally).
Safety data will include single 12-lead electrocardiogram (ECG) readings obtained at each timepoint during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
Pharmacokinetic (PK) profile GSK2315698 and GSK2398852 was performed to evaluate PK of single doses of GSK2398852 and GSK2315698 when co-administered.
The main measure of dose response will be determined by information from part A (and Part A extension if required). The options are: -Volume of distribution of gadolinium in the spleen as a measure of amyloid load (EqMRI); and -Liver histology examination for presence of giant cells, activation of macrophages, and amyloid clearance.
| Arm | Type | Description |
|---|---|---|
| Part A Arm | EXPERIMENTAL | Two subjects in Part A will receive starting dose level of GSK2398852 as 5 milligram (mg) \[approximately equivalent to 0.1 mg/kilogram (kg)\]. The next escalation dose levels in two subjects each are proposed as 1 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg. GSK2315698 will be administered at variable dosed until the concentration of the SAP mAb has fallen below 100 ng/mL. |
| Part B Arm | EXPERIMENTAL | The precise selection of numbers of subjects and dose levels in Part B will be informed by the results from Part A. |
| Name | Type | Description |
|---|---|---|
| GSK2398852 | DRUG | Unit dose strength: 100 mg/mL provided as 1 mL solution per vial. GSK2398852 dosage levels variable with the proposed starting dose level of GSK2398852 as 5 mg \[approximately equivalent to 0.1 mg/ kg\]. The next escalation dose levels are proposed as 1 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg. |
| GSK2315698 | DRUG | Unit dose strength: 200 mg/mL stock to be diluted. GSK2315698 will be administered at variable dosed until the concentration of the serum amyloid P component monoclonal antibody (SAP mAb) has fallen below 100 ng/mL. |
Inclusion Criteria: * Subject has been medically diagnosed with systemic amyloidosis and falls into one of the patient groups (small to moderate amyloid load involving the spleen for Part A; moderate to large amyloid load involving the spleen (to a moderate/large extent) for Part A (following agree...