SAP Depleter Dose Assessment Study in Patients

Study Overview
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Brief Summary
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This study aims to provide safety information on the ligand, GSK2315698A. The pharmacokinetics and pharmacodynamics of the ligand will be determined together with the differences in routes of dose administration, namely the tolerability between intravenous versus subcutaneous dose administration. The study will be carried out in patients with systemic amyloidosis and the ability of GSK2315698A in depleting levels of serum amyloid protein (SAP) will be measured.

Detailed Description
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This study is an open label, dose characteristic study assessing safety and pharmacokinetic and pharmacodynamic considerations of GSK2315698A. GSK2315698A is a ligand known to bind to serum amyloid protein (SAP), a key component of an anti-SAP approach to the treatment of systemic amyloidosis. Safety assessments will include adverse events, vital signs, ECGs and other relevant clinical laboratory tests. Dose administration routes will also be determined focusing on the tolerability of intravenous dose administration versus subcutaneous. The study aims to recruit up to 30 patients with a medical diagnosis of systemic amyloidosis. Subjects will be asked to attend 2 dosing sessions, each session will involve an intravenous infusion of GSK2315698A over 48 hours followed by a single subcutaneous dose in session 1 and up to 3 subcutaneous doses in session 2 to be administered over a 24 hour period.

Official Title
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A Phase 1, Open Label, Dose Characteristic Study to Investigate the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Intravenous and Subcutaneous Doses of GSK2315698A in Patients With Systemic Amyloidosis

Conditions
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Amyloidosis

Intervention / Treatment
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* Drug: GSK2315698


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: medically diagnosed with systemic amyloidosis AST,ALT, alkaline phosphatase <= 3xULN and bilirubin ,1.5xULN undergone radio-labelled-SAP scanning as part of their routine clinical care male or female between 18 and 80 years of age inclusive, at time of signing the informed consent subject is ambulant and capable of attending CUC capable of giving written consent, which includes compliance with the requirements of the requirement and restrictions listed in the consent form a female subjects is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea male subjects with female partners of child-bearing potential must agree to use contraception methods listed in the protocol and informed consent information. This must be followed from the time of the first dose of study medication to 85 days post-last dose. smokers (<10 cigarettes a day) are permitted but must be willing to abstain for the duration of residential study sessions Exclusion Criteria: a positive pre-study Hepatitis B surface antigen or Hepatitis C antibody result within 3 months of screening the subject has participated in a clinical trial and has received an investigational therapeutic product (unlicensed) within 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing lactating females unwillingness or inability to follow the procedures outlined in the protocol subject is mentally or legally incapacitated renal failure requiring haemodialysis will normally result in exclusion. Subjects in patient group 4 on haemodyalysis may be considered providing their schedule of dialysis can be accommodated within the study schedule decompensated cardiac failure or recent history of syncope clinically significant anaemia - Hb<9g/dL use of prohibited medications poor or unsuitable venous access subjects with a QTc of > or equal to 480ms or other ECG abnormalities which, in the opinion of the investigator, is clinically significant in that they may increase safety risk uncontrolled hypertension with systolic BP> 170mm Hg and/or diastolic >100 mm Hg previous surgical procedures that result in altered anatomy of the upper digestive tract including cholecystectomy (gall bladder removal) will result in exclusion from the Entero-Test procedure, but the subject may still participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intravenous infusion for approximately 48 hours followed by subcutaneous injection | Drug: GSK2315698<br>* Intravenous infusion for approximately 48hours followed by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood concentrations of SAP | comparison of predicted vs observed | 19 weeks | 
| Plasma concentrations of GSK2315698 | changes in plasma concentrations of GSK2315698 over time | 19 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of GSK2315698 | evaluated by adverse event (AE) reporting, clinical laboratory tests, vital signs, and 12-lead electrocardiogram (ECG). | 19 weeks | 
| Change from baseline in blood SAP levels | evaluate effect of GSK2315698 on SAP levels in the blood | 19 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Patient, Systemic Amyloidosis, Amyloidosis