SAP Depleter Dose Assessment Study in Patients

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 1

Conditions

Amyloidosis

Treatments

Drug: GSK2315698

Study type

Interventional

Funder types

Industry

Identifiers

NCT01406314

114527

Details and patient eligibility

About

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.

Full description

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.

Enrollment

17 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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