Clinical Trial: A Study to Evaluate the Safety of GSK2398852 When Co-administered With GSK2315698 in Patients With Systemic Amyloidosis
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Single Dose First in Human Study of GSK2398852 Co-Administered With GSK2315698 in Patients With Systemic Amyloidosis
Brief Summary:
The study will be conducted in two parts. The first (Part A) will be an open label single dose escalation part beginning with the proposed starting dose level of GSK2398852 as 5 milligram (mg) [approximately equivalent to 0.1 mg/kilogram (kg)]. The next escalation dose levels are proposed as 1 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg. GSK2315698 will be administered at variable doses until the concentration of the serum amyloid P component monoclonal antibody (SAP mAb) has fallen below 100 nanogram/millilitre (ng/mL). Decisions about these next dose levels will be made following safety review of the prior subjects' data; dose levels may be changed (increased and lowered) and dose levels may be repeated depending on the observed safety such that Part A extension study may be performed. In addition, pharmacokinetics of GSK2315698 (SAP depleter) and GSK2398852 (anti-SAP mAb), and circulating SAP concentrations will be assessed. Dose escalation in Part A will continue to the highest well tolerated dose or the highest allowable dose. Subjects will be closely monitored and will undergo Equilibrium contrast Magnetic Resonance Imaging (EqMRI) including organ volume, Elastography and Liver Biopsy if required.
Part B will be a randomized partially blinded part with the principal objective of assessing the dose response of the GSK2398852 in more detail. Subjects will be assigned to one of approximately 5 dose groups from Part A. The precise selection of numbers of subjects and dose levels will be informed by the results from Part A.
Detailed Summary:
Sponsor: GlaxoSmithKline
Current Primary Outcome:
- Safety of GSK2398852 as assessed by number of subjects with AEs in Part A and in Part B [ Time Frame: Continuous throughout the study ]Adverse events (AEs) will be collected from the start of Study Treatment and until the follow-up contact.
- Safety of GSK2398852 as assessed by clinical laboratory tests in Part A and in Part B [ Time Frame: At scheduled intervals upto Day 42 in each Part. ]Safety data will include assessments of clinical laboratory tests (hematology, clinical chemistry and urinalysis).
- Safety of GSK2398852 as assessed by vital signs measurements in Part A and in Part B [ Time Frame: At scheduled intervals upto Day 42 in each Part. ]Safety data will include measurements of vital signs (semi supine systolic and diastolic blood pressure, pulse rate and temperature measured orally).
- Safety of GSK2398852 as assessed by ECG readings in Part A and in Part B [ Time Frame: At scheduled intervals upto Day 42 in each Part. ]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.
- PK profile of GSK2315698 and GSK2398852 in Part A and in Part B [ Time Frame: In Part A and Part B on Day -2, Day 1 (pre-dose, 1 hour [hr], 2 hr, 3 hr, 4 hr, 8 hr, 12 hr), Day 2, Day 3, Day 4, Day 6, Day 14, Day 21, Day 42 ]Pharmacokinetic (PK) profile GSK2315698 and GSK
Original Primary Outcome: Same as current
Current Secondary Outcome:
- SAP concentrations measurement [ Time Frame: Baseline, Day -3, Day -2, Day -1, Day 42 in each Part. ]SAP concentrations before administration of GSK2398852 will be measured using Hycult ELISA assay; and SAP concentrations after administration of GSK2398852 will be measured by GSK assay in both Parts.
- Measurement of anti-drug antibodies before and after treatment with GSK2398852 [ Time Frame: Day 1 pre-dose, Day 21, Day 42 in each Part. ]Anti-drug antibodies before and after treatment with GSK2398852 will be measured to assess the immunogenicity of GSK2398852 when co-administered with GSK2315698.
Original Secondary Outcome: Same as current
Information By: GlaxoSmithKline
Dates:
Date Received: January 24, 2013
Date Started: May 13, 2013
Date Completion:
Last Updated: May 5, 2017
Last Verified: May 2017
- SAP concentrations measurement [ Time Frame: Baseline, Day -3, Day -2, Day -1, Day 42 in each Part. ]