SAP Depleter Dose Assessment Study in Patients

• ClinicalTrials.gov Identifier: NCT01406314
• Recruitment Status: Completed
• First Posted: August 1, 2011
• Last Update Posted: June 9, 2017
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Amyloidosis	Drug: GSK2315698	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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
• Actual Study Start Date: October 13, 2011
• Actual Primary Completion Date: November 14, 2012
• Actual Study Completion Date: November 14, 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention; Intravenous infusion for approximately 48 hours followed by subcutaneous injection	Drug: GSK2315698; Intravenous infusion for approximately 48hours followed by subcutaneous injection

Outcome Measures

Primary Outcome Measures :

1. Blood concentrations of SAP [ Time Frame: 19 weeks ]
   comparison of predicted vs observed
2. Plasma concentrations of GSK2315698 [ Time Frame: 19 weeks ]
   changes in plasma concentrations of GSK2315698 over time

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United Kingdom

GSK Investigational Site

Cambridge, United Kingdom, CB2 2GG

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01406314
• Other Study ID Numbers: 114527
• First Posted: August 1, 2011
• Last Update Posted: June 9, 2017
• Last Verified: June 2017

Keywords provided by GlaxoSmithKline:

Phase 1; Patient; Systemic Amyloidosis; Amyloidosis

Additional relevant MeSH terms:

Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases