
    change in benefit/risk profile.
  
['amyloidosis']
['gsk2315698 (cphpc)', 'gsk2398852 (unlabeled anti-sap mab)', '89zr-gsk2398852 (89zr-labeled anti-sap mab)']

        Inclusion Criteria:

          -  Subject must be 65 to 80 years of age inclusive, at the time of signing the informed
             consent.

          -  Subjects with a diagnosis of ATTR-CM: a) Wild-type ATTR status must be confirmed by
             genotyping and have one of the following: i) Definite histochemical identification of
             amyloid by Congo red staining and green birefringence in crossed polarized light in
             cardiac or other tissue biopsy and identification of Transthyretin amyloidosis (TTR)
             as the amyloid fibril protein either by immunohistochemistry or proteomic analysis OR
             ii) Scintigraphy Technetium-99m-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid
             (99mTc-DPD) with confirmed myocardial uptake. b) Hereditary ATTR amyloidosis (example,
             TTR Val30Met) should have a known amyloidogenic TTR mutation demonstrated by
             genotyping and is recognized to be primarily associated with cardiomyopathy and one of
             the following: i) Definite histochemical identification of amyloid by Congo red
             staining and green birefringence in crossed polarized light in cardiac or other tissue
             biopsy and identification of TTR as the amyloid fibril protein either by
             immunohistochemistry or proteomic analysis. ii) Scintigraphy: 99mTc-DPD with confirmed
             myocardial uptake.

          -  Both male and female subjects are eligible to participate. a) Male subjects: A male
             subject must agree to use contraception during the treatment period and for at least 3
             months after the last scan and refrain from donating sperm during this period. b)
             Female subjects: A female subject is eligible to participate if she is not of
             childbearing potential.

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and protocol.

          -  New York Heart Association (NYHA) up to class 3; subjects should be clinically stable
             for at least 3 months preceding to Screening.

        Exclusion Criteria:

          -  Cardiomyopathy primarily caused by non-amyloid diseases (example, ischemic heart
             disease; valvular heart disease).

          -  Interval from the Q wave on the ECG to point T using Fredericia's formula (QTcF) >500
             milliseconds (msec).

          -  Sustained (at a rate of >=120 beats per minute for >=30 seconds), or symptomatic
             monomorphic ventricular tachycardia (VT), or rapid polymorphic VT, at
             Screening/Baseline cardiac monitoring.

          -  Systolic blood pressure <=100 millimeters of mercury (mm/Hg) based on triplicate
             readings at Screening.

          -  Unstable heart failure defined as emergency hospitalization for worsening, or
             decompensated heart failure, or syncopal episode within 1 month of screening.

          -  Implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM) at Screening.

          -  Estimated Glomerular filtration rate (eGFR) at Screening <50 milliliters per minute
             (mL/min) calculated using modification of diet in renal disease (MDRD).

          -  Any active and persistent dermatological condition, which in the opinion of the
             Investigator and Medical Monitor would preclude safe participation.

          -  History of allogeneic stem cell transplantation, prior solid organ transplant, or
             anticipated to undergo solid organ transplantation, or left ventricular assist device
             (LVAD) implantation.

          -  Malignancy within last 5 years, except for basal or squamous cell carcinoma of the
             skin, or carcinoma in situ of the cervix that has been successfully treated.

          -  Acute coronary syndrome, or any form of coronary revascularization procedure
             (including coronary artery bypass grafting [CABG]), within 6 months of screening.

          -  Symptomatic, clinically significant autonomic neuropathy which the Principal
             Investigator (PI) feels will preclude administration of study treatment.

          -  Uncontrolled hypertension during Screening.

          -  ALT >3 times upper limit of normal (ULN) OR bilirubin >1.5 times ULN (isolated
             bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct
             bilirubin <35%).

          -  Peripheral edema at Screening that in the opinion of the PI or designee might prevent
             adequate absorption of subcutaneously administered CPHPC.

          -  Presence of any co-morbid (example, steroid refractory rheumatoid arthritis), or an
             uncontrolled medical condition (example, diabetes mellitus), which in the opinion of
             the investigator would increase the potential risk to the subject. Investigator should
             liaise with the Medical Monitor where there is uncertainty as to the eligibility of a
             subject.

          -  Positive test for hepatitis B, hepatitis C and/or human immunodeficiency virus (HIV)
             during Screening, or within 3 months prior to first dose of study treatment.

          -  Clinically significant multiple or severe drug allergies, intolerance to topical
             corticosteroids, or severe post-treatment hypersensitivity reactions (including, but
             not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis,
             toxic epidermal necrolysis and exfoliative dermatitis).

          -  Inability to comprehend and/or understand the study patient information sheet, and/or
             unwillingness or inability to follow the procedures outlined in the protocol.

          -  Has any of the following: a) Fulfillment of diagnostic criteria for Amyloid
             Light-chain (AL) amyloidosis. b) Fulfillment of diagnostic criteria for amyloid A (AA)
             or non-TTR hereditary amyloidosis.

          -  ATTR Disease Load: c) Histologically proven or clinically suspected gastrointestinal
             TTR amyloidosis; d) Diffuse skeletal muscle uptake of 99m(Tc)-DPD on Single-photon
             emission computed tomography (SPECT) imaging (where available); e) Peripheral
             neuropathy causing more than mild morbidity (example, walking disability; neuropathic
             pain affecting activities of daily living); f) Proven or clinically suspected
             intracranial TTR involvement including ophthalmological disease.

          -  Non-amyloidosis related chronic liver disease (with the exception of Gilbert's
             syndrome or clinically asymptomatic gallstones).

          -  Participation in a separate clinical trial involving CPHPC within 3 months of
             Screening.

          -  Any prohibited concomitant medication within referenced timeframe.

          -  Treatment with another investigational drug, biological agent, or device within 6
             months of screening, or 5 half-lives of the study agent, whichever is longer.

          -  Orthopnea of sufficient severity to preclude supine scanning as determined at
             Screening.

          -  Inability to fit inside scanner due to body size (girth).

          -  History of claustrophobia.

          -  Contraindication to magnetic resonance imaging (MRI) contrast agents.

          -  Contraindication for MRI scanning (as assessed by local MRI safety questionnaire),
             which includes but is not limited to: a) Intracranial aneurysm clips (except Sugita)
             or other metallic objects; b) Intra-orbital metal fragments that have not been
             removed; c) Pacemakers or other implanted cardiac rhythm management/monitoring devices
             and non-magnetic resonance (MR) conditional heart valves; d) Inner ear implants.

          -  Donation of blood or blood products in excess of 500 milliliters (mL) within 84 days
             of Screening.

          -  Poor or unsuitable venous access.
      