Saves the questions and what to expect into your notes, next to the visit they belong to.
Keep this study
Lead
GlaxoSmithKline
Age
18–80
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
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).
Interval from the Q wave on the ECG to point T using Fredericia's formula (QTcF) \> 500 millisecond (msec)
Sustained / symptomatic monomorphic ventricular tachycardia (VT), or rapid polymorphic VT, 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
Any active and persistent dermatological condition
Existing diagnosis of any type of dementia
History of allogeneic stem cell transplantation, prior solid organ transplant, or anticipated to undergo solid organ transplantation, or left ventricular assist device (LVAD) implantation, during the course of the study.
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.
Stroke within 6 months of screening, or transient ischaemic attack (TIA) within 3 months of screening
Symptomatic, clinically significant autonomic neuropathy which the Principal Investigator (PI) feels will preclude administration of study treatment
Hypoalbuminaemia (serum albumin \< 30 g/L)
Uncontrolled hypertension during screening
Alanine transaminase ALT \>3x upper limit of normal (ULN) AND bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
Peripheral oedema at Screening that in the opinion of the Prinicpal Investigator (PI) or designee might prevent adequate absorption of subcutaneously administered CPHPC
Urine dipstick positive (\>1+) for blood during screening with investigation indicating glomerular haematuria. If other causes are identified, subjects may be enrolled on resolution of the abnormality
Presence of any co-morbid or an uncontrolled medical condition (e.g. 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 patient
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
Unwillingness or inability to follow the procedures outlined in the protocol
Use of GSK2315698 (CPHPC), or participation in a separate clinical trial involving CPHPC within 3 months of screening
Any prohibited concomitant medication as per protocol within 28 days of Screening
Donation of blood or blood products in excess of 500 mL within 84 days of screening
Lactating females
Poor or unsuitable venous access
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.
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 CARDIAC MAGNETIC RESONANCE (CMR) SCANNING
Orthopnoea of sufficient severity to preclude supine scanning as determined at screening
Contraindication to magnetic resonance imaging (MRI) contrast agents
Inability to fit inside scanner due to body size (girth)
Contraindication for MRI scanning (as assessed by local MRI safety questionnaire), which includes but is not limited to:
* Intracranial aneurysm clips (except Sugita) or other metallic objects
* Intra- orbital metal fragments that have not been removed
* Pacemakers or other implanted cardiac rhythm management/monitoring devices and non-MR conditional heart valves
* Inner ear implants
* History of claustrophobia
99m\^TC-PYP OR 99mTC-DPD BONE TRACER RADIOSCINTOGRAPHY
Orthopnoea of sufficient severity to preclude supine scanning as determined at Screening
Previous allergic reaction to radioisotope bone tracers
Previous inclusion in a research protocol involving nuclear medicine, positron emission tomography (PET) or radiological investigations with significant radiation burden (a significant radiation burden being defined as 10 mSv in addition to natural background radiation, in the previous 3 years).
Has any of the following:
Fulfilment of diagnostic criteria for AL amyloidosis
TTR polyneuropathy and / or intracranial TTR involvement including ophthalmological disease
Non-amyloidosis related chronic liver disease (with the exception of Gilbert's syndrome or clinically asymptomatic gallstones)
Platelet count \< 125x10\^9 / L
Chronic liver disease or current active liver or biliary disease not attributable to amyloidosis (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Chronic liver disease or current active liver or biliary disease not attributable to amyloidosis (with the exception of Gilbert's syndrome or asymptomatic gallstones).
