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| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
| Ionis Pharmaceuticals, Inc. | INDUSTRY |
ATTRwt (also known as senile systemic, or senile cardiac amyloidosis) is a progressive heart disease, causing congestive heart failure. It is caused by amyloid protein deposits in the heart, that are derived from a normal protein, TTR, made in the liver. The aim of the study is to determine whether lowering the blood levels of TTR, by a weekly injection of a compound designed specifically to do this, will slow the progression of the disease when treated patients are compared to previously-followed patients who were not receiving this drug. The study also aims to determine how well this drug is tolerated and the existence and severity of any drug side-effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental Drug | Experimental | Isis 420915/GSK 299872, an antisense oligonucleotide. Administered subcutaneously three times per week for the first week, and then weekly for 18 months. Each dose shall contain 300 mg of active drug. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isis 420915/GSK 299872 | Drug | Open label study in comparison to historic control. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Systolic strain imaging by echocardiographic speckle tracking | The primary echocardiographic parameter to be measured will be longitudinal left ventricular (LV) strain (units = % LV longitudinal shortening) as compared to baseline. | Month 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Systolic strain evaluation by echocardiography | The primary echocardiographic parameter measured will be longitudinal left ventricular (LV) strain (units = %). | Secondary analysis will occur at 18 months |
| Echocardiographic determination of Mean thickness of LV septum and posterior wall (units = mm) |
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All patients with documented SSA will be considered for inclusion. SSA is defined as an echocardiographic appearance of left ventricular wall thickness of 13 mm or more, in the absence of uncontrolled hypertension, and with a positive biopsy for amyloid, which also stains positive for TTR by immunochemistry or mass spectrometry. For the definition of SSA, genetic testing should be negative for a mutation. Identification of amyloid type is standard of care for all patients seen at the Cardiac Amyloidosis Program and the presence of a clinically -obtained positive biopsy will be a requirement for study inclusion. The positive biopsy can be from any organ, providing that the echocardiographic appearance is typical of amyloidosis.
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rodney H Falk, MD | Brigham and Women's Hospital | Principal Investigator |
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| ID | Term |
|---|---|
| D000686 | Amyloidosis |
| ID | Term |
|---|---|
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D016376 | Oligonucleotides, Antisense |
| ID | Term |
|---|---|
| D016375 | Antisense Elements (Genetics) |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D015341 | Nucleic Acid Probes |
| D009696 | Nucleic Acids |
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| 12 months |
| Echocardiographic determination of Mean thickness of LV septum and posterior wall (units = mm) | 18 months |
| Echocardiographic determination of LV ejection fraction (units = %) | 12 months |
| Echocardiographic determination of LV ejection fraction (units = %) | 18 months |
| LV mass measurement by Cardiac MRI (cMRI) (units = grams) | 18 months |
| LV cellular component as determined by cMRI (units = % of total LV mass) | 12 months |
| LV cellular component as determined by cMRI (units = % of total LV mass) | 18 months |
| LV extracellular component as determined by cMRI (units = % of total LV mass) | 12 months |
| LV extracellular component as determined by cMRI (units = % of total LV mass) | 18 months |
| Extent of cMRI late gadolinium enhancement of the LV (unites = % of area) | 12 months |
| Extent of cMRI late gadolinium enhancement of the LV (unites = % of area) | 18 months |
| LV mass measurement by Cardiac MRI (cMRI) (units = grams) | Month 12 |
| D009841 | Oligonucleotides |
| D011119 | Polynucleotides |
| D009711 | Nucleotides |
| D015335 | Molecular Probes |
| D019995 | Laboratory Chemicals |
| D020313 | Specialty Uses of Chemicals |
| D020164 | Chemical Actions and Uses |