A Safety Study of GSK3039294 in Healthy Volunteers and Patients With Systemic Amyloidosis

Inclusion Criteria:

* Age: 18 to 70 years of age inclusive at the time of signing the informed consent.
* Non-smokers and Smokers. Smokers (\<5 /day) are permitted but must be willing to abstain for the duration of residential study sessions and / or dosing period (whichever is longer).
* Body weight \>50 kilograms (kg) and body mass index (BMI) within the range 18.5-32 kg/square meter (m\^2) (inclusive) and excluding the effects of peripheral oedema.
* Male or female
* Female subjects are eligible to participate if they are of non-childbearing potential defined as premenopausal females with a documented tubal ligation or hysterectomy or bilateral oophorectomy; or postmenopausal defined as 12 month of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli-international units (MIU)/milliliter (mL) and estradiol \< 40 picograms (pg)/mL (147 picomoles \[pmol\]/liter \[L\]) is confirmatory
* Male subjects with female partners of child bearing potential must comply with one of the following contraception requirements from the time of first dose of study medication until completion of the follow-up visit: (a.) Vasectomy with documentation of azoospermia; (b.) Male condom plus partner use of one of the following contraceptive options: Contraceptive subdermal implant that meets the effectiveness criteria of a \<1% rate of failure per year, as stated in the product label, Intrauterine device or intrauterine system that meets the standard operating procedure (SOP) effectiveness criteria including a \<1% rate of failure per year, as stated in the product label, Oral Contraceptive either combined or progestogen alone, Injectable progestogen, Contraceptive vaginal ring, Percutaneous contraceptive patches, Occlusive cap (female diaphragm or cervical/vault cap) with a vaginal spermicide (foam, gel, cream or suppository). These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
* Additional Inclusion Criteria - Healthy Volunteers: Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
* Additional Inclusion Criteria - Healthy Volunteers: A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* Additional Inclusion Criteria - Healthy Volunteers: aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase and bilirubin \<=1.5 upper limit of normal (ULN) (isolated bilirubin \>1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
* Additional Inclusion Criteria - Patients: Subject medically diagnosed with systemic amyloidosis
* Additional Inclusion Criteria - Patients: serum amyloid P component (SAP) scan identifying amyloid at any anatomical site, including subset of patients with moderate-large amyloid load in the liver
* Additional Inclusion Criteria - Patients: Up to and including New York Heart Association (NYHA) class 2 with a stable clinical cardiac status 12 weeks prior to screening
* Additional Inclusion Criteria - Patients: For Amyloid Light-chain (AL) amyloidosis patients, \>=12 months post-chemotherapy with a stable free light chain (FLC) ratio in the preceding 4 months
* Additional Inclusion Criteria - Patients: estimated glomerular filtration rate (eGFR) \>50 mL/minute
* Additional Inclusion Criteria - Patients: Alanine amino transferase (ALT) \<=3x upper limit of normal (ULN) and bilirubin \<=1.5x ULN (isolated bilirubin \>1.5 xULN is acceptable if bilirubin was fractionated and direct bilirubin \<35%), irrespective of alkaline phosphatase (ALP) level
* Additional Inclusion Criteria - Patients: Subject is ambulant and capable of attending the clinical unit

Exclusion Criteria:

* Prohibited medication
* History of regular alcohol consumption within 6 months of the study defined as: For United Kingdom (UK )sites - healthy volunteers: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* History of sensitivity to any of the study medications, or metabolite thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
* A positive pre-study drug/alcohol screen
* A positive test for human immunodeficiency virus (HIV) antibody
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 84 days
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). Prior to Part A for subjects participating in Parts A and B
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day Lactating females
* Poor or unsuitable venous access
* Additional Exclusion Criteria - Healthy Volunteer: Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
* Additional Exclusion Criteria - Healthy Volunteer: corrected QT interval using Fridericia's formula (QTcF) \>450 milliseconds (msec) from a mean of triplicate readings triplicate readings taken 5 minutes apart
* Additional Exclusion Criteria - Patients: Subject with mean QTcF of \>480 msec from a mean of triplicate readings
* Additional Exclusion Criteria - Patients: First degree heart block deemed to require pacing; Second degree atrioventricular (AV) block Mobitz Type II; Trifasicular block; Ventricular tachyarrthymias - with the exception of bundle branch block, atrial fibrillation \& first degree heart block not requiring pacing, or second degree AV block Mobitz Type I
* Additional Exclusion Criteria - Patients: 24 hour proteinuria \>=5 g
* Additional Exclusion Criteria - Patients: A syncopal episode, of any causation, within 4 weeks of screening
* Additional Exclusion Criteria - Patients: Average systolic blood pressure (SBP) \<=90 millimeter of mercury (mmHg) at Screening from triplicate readings
* Additional Exclusion Criteria - Patients: Implantable cardiac defibrillator (ICD)
* Additional Exclusion Criteria - Patients: Evidence of severe cardiac dysfunction within 12 months of screening, as diagnosed by a cardiologist, using Echocardiography or cardiac magnetic resonance imaging (MRI) i.e. markedly impaired ejection fraction (EF) (EF \< 50% for cardiac amyloidosis patients), or cardiac imaging parameters of severe diastolic dysfunction (grade 3 or 4)
* Additional Exclusion Criteria - Patients: Anaemia hemoglobin \<9 g/deciliter (dL)
* Additional Exclusion Criteria - Patients: Uncontrolled hypertension in a known hypertensive patient, or fulfilling diagnostic criteria of essential hypertension at screening
* Additional Exclusion Criteria - Patients: Presence of any co-morbid condition (e.g. severe or unstable coronary artery disease; moderate to severe chronic obstructive pulmonary disease) which in the opinion of the investigator would increase the potential risk to the subject
* Additional Exclusion Criteria - Patients: Non-amyloidosis causes of chronic liver disease (with the exception of Gilbert's syndrome or clinically asymptomatic gallstones)
* Additional Exclusion Criteria - Patients: Diabetes Mellitus
* Additional Exclusion Criteria - Patients: Glycosuria at Screening
* Additional Exclusion Criteria - Patients: Urine power of Hydrogen (pH) \<6.0 at screening
* Additional Exclusion Criteria - Patients: Hypoalbuminemia (\<30 nanomoles \[nmol\]/L)
* Additional Exclusion Criteria - Patients: Hypophosphatemia (less than 0.8 millimoles \[mmol\]/L)
* Additional Exclusion Criteria - Patients: Prothombin time \>1.5xULN
* Additional Exclusion Criteria - Patients: Malabsorption syndrome of any aetiology
* Additional Exclusion Criteria - Patients: Compassionate use of CPHPC (GSK2315698) or participation in a separate clinical trial involving CPHPC within 3 months of screening
* Additional Exclusion Criteria - Patients: Currently taking any of the following esterase-cleaved prodrug medications: cerebyx, aquavan, spectracef, hepsera, viread
* Additional Exclusion Criteria - Patients: Anticoagulation therapy within 4 weeks of Screening
* Additional Exclusion Criteria - Patients: Currently receiving or have received within 12 weeks of screening immunosuppressive anti-cytokine monoclonal antibodies (e.g. anti-tumor necrosis factor \[anti-TNF\] or anti-interleukin 1\[anti-IL-1\]), disease modifying drugs (e.g. methotrexate, gold or cyclophosphamide), or high-dose infusional steroids (e.g. methylprednisolone), with the exception of low-dose maintenance oral corticosteroids (e.g. \<=30 milligrams (mg) prednisolone per day)