Clinical trial NCT01406314: SAP Depleter Dose Assessment Study in Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyloidosis
Keywords: Phase 1
Patient
Systemic Amyloidosis
Amyloidosis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-08-01
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Blood concentrations of SAP
timeFrame: 19 weeks
measure: Plasma concentrations of GSK2315698
timeFrame: 19 weeks
Secondary outcomes:
measure: safety and tolerability of GSK2315698
timeFrame: 19 weeks
measure: Change from baseline in blood SAP levels
timeFrame: 19 weeks
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: