Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy) MedDRA version: 20.0 Level: PT Classification code 10007509 Term: Cardiac amyloidosis System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Onpattro
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PATISIRAN
CAS Number: 1386913-72-9
Current Sponsor code: ALN-TTR02
Other descriptive name: patisira
Sponsors
Alnylam Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 (or age of legal consent, whichever is older) to 85 years, inclusive. 2. Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy: Hereditary ATTR amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria: a. TTR pathogenic mutation consistent with hATTR. b. Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness >12 mm (based on central echocardiogram reading at screening). c. Amyloid deposits in cardiac or noncardiac tissue (eg, fat pad aspirate, salivary gland, median nerve connective sheath) confirmed by Congo Red (or equivalent) staining OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid [DPD-Tc], 99mTc-pyrophosphate [PYP-Tc], or 99mTc-hydroxymethylene diphosphonate [HMDP]) with Grade 2 or 3 cardiac uptake, if monoclonal gammopathy of undetermined significance (MGUS) has been excluded. d. If MGUS, confirm TTR protein in tissue with immunohistochemistry (IHC) or mass spectrometry. Wild-type ATTR amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria: a. Absence of pathogenic TTR mutation. b. Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness >12mm (based on central echocardiogram reading at screening). c. Amyloid deposits in cardiac tissue with TTR precursor identification by IHC, mass spectrometry, OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid [DPD-Tc], 99mTc-pyrophosphate [PYP-Tc], or 99mTc-hydroxymethylene diphosphonate [HMDP]) with Grade 2 or 3 cardiac uptake, if MGUS has been excluded. d. If MGUS, confirm TTR protein in cardiac tissue with IHC or mass spectrometry 3. Medical history of HF with at least 1 prior hospitalization for HF (not due to arrhythmia or a conduction system disturbance treated with a permanent pacemaker) OR clinical evidence of HF (with or without hospitalization) manifested by signs and symptoms of volume overload or elevated intracardiac pressures (eg, elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that currently requires treatment with a diuretic. 4. Patient meets one of the following criteria: a. Tafamidis naïve; in addition to patients who have never taken tafamidis, those who have been on tafamidis for =30 days total and have not received any tafamidis in the 6 months prior to baseline will be considered tafamidis naïve and may qualify for the study. b. Currently on tafamidis (for =6 months) and has demonstrated disease progression, as determined by the Investigator. (At the time of study entry, tafamidis treatment must be on-label use of commercial tafamidis for the treatment of ATTR amyloidosis with cardiomyopathy at the approved dose in the country of use.) 5. Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomization, as assessed by the Investigator. 6. Able to complete =150 m on the 6-MWT at screening. 7. Screening NT-proBNP >300 ng/L and 600 ng/L and <8500 ng/L. 8. Patient is able to understand and is willing and able to comply with the stu
Exclusion criteria
Exclusion criteria: 1. Has known primary amyloidosis (AL) or leptomeningeal amyloidosis. 2. NYHA Class III AND ATTR amyloidosis disease Stage 3 (defined as both NT-proBNP >3000 ng/L and estimated glomerular filtration rate [eGFR] 2.0 × the upper limit of normal (ULN). b. Total bilirubin >2 × ULN. c. International normalized ratio (INR)>1.5 (unless patient is on anticoagulant therapy, in which case excluded if INR>3.5). 6. Has eGFR 180 mmHg) and diastolic (>100 mmHg) blood pressure that is considered uncontrolled by ph
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of patisiran compared with placebo treatment on functional capacity (6-minute walk test [6-MWT]) in patients with ATTR amyloidosis with cardiomyopathy;Secondary Objective: To evaluate the efficacy of patisiran compared with placebo treatment on: - Health status and health-related quality of life - Patient mortality, hospitalizations and urgent heart failure (HF) visits ;Primary end point(s): Change from baseline at Month 12 in 6-MWT;Timepoint(s) of evaluation of this end point: Double blind period: Month 12; this assessment will also be performed at Month 6 (Weeks 25-26) and Month 9 (Weeks 37-38) Open label extension period: Year 2 weeks 79-80, weeks 91-92, weeks 106-107; Year 3 weeks 133-134, weeks 145-146, weeks 157-158; Year 4 weeks 184-185, weeks 208-209. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Change from baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score -Composite endpoint of all-cause mortality, frequency of cardiovascular (CV) events (CV hospitalizations and urgent HF visits) and change from baseline in 6-MWT over the 12-month double-blind period -Composite endpoint of all-cause mortality and frequency of all-cause hospitalizations and urgent HF visits over the 12-month double-blind period ;Timepoint(s) of evaluation of this end point: Double blind period: Month 12 (Weeks 52-53); this assessment will also be performed at Month 6 (Weeks 25-26) and Month 9 (Weeks 37-38) Open label extension period: Year 2 weeks 79-80, weeks 91-92, weeks 106-107; Year 3 weeks 133-134, weeks 145-146, weeks 157-158; Year 4 weeks 184-185, weeks 208-209. | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Chile, Czech Republic, Denmark, Hong Kong, Italy, Japan, Korea, Democratic People's Republic of, Mexico, Netherlands, New Zealand, Portugal, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trials Information Line
Alnylam Pharmaceuticals, Inc
Outcome results
None listed