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

Stopped early · Phase 2

Conditions studied: Amyloidosis

In brief

The study is intended to evaluate whether monthly repeated courses of administration of GSK2315698 followed by GSK2398852 is associated with a reduction in cardiac amyloid load in patients with cardiac amyloidosis, monitored by cardiac magnetic resonance imaging (CMR) and echocardiography (ECHO), and whether this is associated with an improvement in cardiac function. Cohort 1 is transthyretin cardiomyopathy (ATTR-CM) , cohort 2 is patients with immunoglobulin light chain (AL) systemic amyloidosis at greater than 6 months post chemotherapy, cohort 3 newly diagnosed AL systemic amyloidosis undergoing chemotherapy. Primary objectives for the study are assessment of reduction in cardiac amyloid load after repeated administrations of Anti-SAP treatment as evaluated by CMR in all study groups and assessment of safety \& tolerability of repeated administration of Anti-SAP treatment, including compatibility with chemotherapy treatment in patients with AL systemic amyloidosis. This is an open label, non-randomised, three-group, monthly repeat Anti-SAP treatment study in systemic amyloidosis patients with cardiac dysfunction caused by cardiac amyloidosis. Subjects will receive up to 6 courses of Anti-SAP treatment. Maximum total duration for a subject in the study is approximately 18 months.

Key facts

Study ID

NCT03044353

Run by

GlaxoSmithKline

People needed

7

Starts

2017-07-10

Expected to finish

2019-01-03

Last updated by the study team

2019-10-16

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify 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
• LV mass on CMR > 200 grams (g) Inclusion Criteria for Group 1
• 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
• Inclusion Criteria for Group 2
• 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

You may not qualify if…

• Cardiomyopathy primarily caused by non-amyloid diseases (e.g. ischemic heart disease; valvular heart disease)
• 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
• N-terminal pro b-type Natriuretic Peptide [(NT)-proBNP] >8500 nanograms (ng)/ Liter (L)
• Glomerular filtration rate (GFR) at Screening < 40 milliliter (mL)/minute (min)
• 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

Where it is running

• GSK Investigational Site — Boston, Massachusetts, United States
• GSK Investigational Site — Cambridge, United Kingdom
• GSK Investigational Site — London, United Kingdom

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.