Transthyretin (TTR) mediated familial amyloidotic cardiomyopathy (FAC) MedDRA version: 18.1 Level: PT Classification code 10016202 Term: Familial amyloidosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: ALN-TTRSC
Product Code: ALN-TTRSC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Revusiran
Current Sponsor code: ALN-TTRSC
Other descriptive name: ALN-51547
Concentrati
Sponsors
Alnylam Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are male or female of 18 to 90 years of age (inclusive). 2. Have a documented TTR mutation. 3. Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining or technetium scintigraphy (99mTc -3,3-diphosphono-1,2-propanodicarboxylic acid [DPD-Tc] or 99mTcpyrophosphate [PYP-Tc]) with Grade 2 or 3 cardiac uptake, centrally confirmed. 4. If patient has monoclonal gammopathy, TTR amyloidosis needs to be confirmed through TTR protein identification by immunohistochemistry or mass spectrometry. 5. Have a medical history of heart failure (HF) with at least 1 prior hospitalization for HF, which may include hospitalization for arrhythmia or pacemaker placement, OR clinical evidence of HF (as evidenced by one or more of the following: elevated jugular venous pressure, peripheral edema, shortness of breath or signs of pulmonary congestion on x-ray or auscultation) that either requires/required treatment with diuretics or is/was associated with an N terminal prohormone of B-type natriuretic peptide (NT-proBNP) >400 ng/L or B-type natriuretic peptide (BNP) >100 ng/L. 6. Have evidence of cardiac involvement by Screening/Baseline echocardiogram including an end-diastolic intraventricular septum thickness of =12 mm. For patients with an end-diastolic intraventricular septum thickness of 3 g/dL (>4.35 µmol/L), and total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Has estimated Glomerular Filtration Rate (eGFR) 2 9. Has untreated hypo- or hyperthyroidism 10. Has a New York Heart Association (NYHA) classification of IV 11. Has known or suspected systemic bacterial, viral, parasitic, or fungal infection 12. Has known human immunodeficiency virus (HIV) infection 13. Current, heavy alcohol use, defined as regular consumption of greater than 2 to 3 units/day for women and 3 to 4 units/day for men (a unit of alcohol equals 1 glass of wine [125 mL], 1 measure of spirits, or ½ pint of beer), or a known history of alcohol abuse within the past 2 years. 14. Has received an investigational agent or device within 30 days of anticipated study drug administration or 5 half-lives of the investigational drug, whichever is longer 15. Is currently taking diflunisal, tafamidis, doxycycline, or tauroursodeoxycholic acid; if previously on any of these agents, must have completed a 14-day wash-out prior to start of study drug administration in this study 16. Had metastatic cancer within the past 5 years 17. History of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc). 18. Has a history of intolerance to SC injection 19. Has other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation 20. Has had a heart or liver transplant, or is being considered for a transplant during the study period 21. Known history of clinically significant chronic liver disease in the opinion of the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy and safety of ALN-TTRSC in patients with FAC.;Secondary Objective: Not applicable;Primary end point(s): The co-primary endpoints of the study are to evaluate the difference between the ALN-TTRSC and placebo groups for: 1. Change in 6-MWD at 18 months compared to baseline 2. Percent reduction in serum TTR burden over 18 months;Timepoint(s) of evaluation of this end point: 1. At 18 months 2. Over 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the study are to determine the effect of ALN-TTRSC on various clinical parameters by assessing the difference between the ALN-TTRSC and placebo groups at 18 months for: • Composite endpoint of CV mortality and CV hospitalization • Change in New York Heart Association (NYHA) class compared to baseline • Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) compared to baseline • Cardiovascular (CV) mortality • CV hospitalization • All-cause mortality;Timepoint(s) of evaluation of this end point: • At 18 months | — |
Countries
Belgium, Brazil, Canada, France, Germany, Italy, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trial Hotline
Alnylam Pharmaceuticals Inc
Outcome results
None listed