Multiple Treatment Session Study to Assess GSK2398852 Administered Following and Along With GSK2315698

Inclusion Criteria

• •Between 18 and 80 years of age inclusive, at the time of signing the informed consent.
• •Male and female.
• •Males:
• •Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication for a cycle of spermatogenesis following five terminal half-lives after the last dose of study medication. Vasectomy with documentation of azoospermia.
• •Male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant, Intrauterine device or intrauterine system, Combined Oral Contraceptive or Injectable progestogen, Contraceptive vaginal ring, Percutaneous contraceptive patches .
• •This is an all-inclusive list of those methods that meet the following GlaxoSmithKline (GSK) definition of highly effective: having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label. For non-product methods (e.g., male sterility), the investigator determines what is consistent and correct use. The GSK definition is based on the definition provided by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
• •The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
• •Females
• •A female subject is eligible to participate if she is not pregnant (as confirmed by a negative Urine human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies:
• •Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy.
• •Postmenopausal defined as: 60 years old; Twelve(12) months of spontaneous amenorrhea with an appropriate clinical profile, e.g. age appropriate, \> 45 years, in the absence of hormone replacement therapy (HRT) or medical suppression of the menstrual cycle (e.g. leuprolide treatment) in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and oestradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels). Females on HRT and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
• •Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (As mentioned in study protocol) from 30 days prior to the first dose of study medication and until 3 months after the last dose of study medication.
• •The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception
• •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• •Late-Gadolinum enhancement (LGE) on CMR indicative of cardiac amyloidosis
• •Transthyretin amyloid (ATTR) cardiomyopathy (CM)
• •Subjects with a diagnosis of hereditary ATTR amyloidosis should have a known amyloidogenic transthyretin (TTR) mutation demonstrated by genotyping AND is recognised to be primarily associated with cardiomyopathy AND one of the following: Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarised light in cardiac or other tissue biopsy and identification of TTR as the amyloid fibril protein either by immunohistochemistry or proteomic analysis.
• •Or Scintigraphy: 99m\^Tc-DPD with Grade 2 cardiac uptake or 99m\^Tc-PYP with either Grade 2 or 3 cardiac uptake.
• •Subjects with a diagnosis of wild type ATTR-CM must be negative by genotyping and have one of the following: Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarised light in cardiac or other tissue biopsy and identification of TTR as the amyloid fibril protein either by immunohistochemistry or proteomic analysis OR Scintigraphy 99m\^Technetium-dicarboxypropane diphosphonate (99m\^Tc-DPD) with Grade 2 cardiac uptake or 99m\^ Technetium-pyrophosphate (99m\^Tc-PYP) with Grade 2 or 3 cardiac uptake.
• •Clinically stable in New York heart association (NYHA) class 2 or 3 for the 3 months preceding screening
• •Subject medically diagnosed with AL amyloidosis that has required chemotherapy or an autologous stem cell transplant based upon:
• •AL amyloidosis confirmed by biopsy with immunohistochemical staining or proteomic identification of AL amyloid fibril type, in subjects with definite monoclonal gammopathy in whom causative mutations of all known relevant amyloidogenic genes have been excluded
• •Clinically stable in NYHA class 2 or 3 for the 3 months preceding screening
• •\>=6 months after completing any line of chemotherapy, or after autologous stem cell transplantation, and having attained either a very good partial response (VGPR) or a complete response (CR), and without the need for haematological maintenance therapies
• •Newly diagnosed AL amyloidosis based upon:
• •AL amyloidosis confirmed by biopsy with immunohistochemical staining or proteomic identification of AL amyloid fibril type in subjects with definite monoclonal gammopathy in whom causative mutations of all known relevant amyloidogenic genes have been excluded
• •Mayo stage II or IIIa
• •Confirmed free light chain complete response (CR) during the first three cycles of first-line chemotherapy where at least the first cycle has been with cyclophosphamide, bortezomib, dexamethasone (CyBorD).