SAP Depleter Dose Assessment Study in Patients
SAP Depleter Dose Assessment Study in Patients
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.
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.
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