Transthyretin (TTR) Cardiac Amyloidosis MedDRA version: 19.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders 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 Spons
Sponsors
Alnylam Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Previously received and tolerated ALN-TTRSC in Study ALN-TTRSC-002; and completed Study ALN-TTRSC-002 through the Day 90 visit 2. Adequate liver function, demonstrated by an aspartate transaminase and alanine transaminase = 2.5 × the upper limit of normal, total bilirubin 3 g/dL (> 4.35 µmol/L) 3. Women of child-bearing potential (WOCBP) must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception prior to Screening/Baseline, throughout study participation, and for 1 month after last dose administration 4. Males who agree to use appropriate means of contraception throughout study participation until 1 month after last dose administration 5. Patient, or patient’s legal representative, is able and willing to provide written informed consent and the patient is willing to comply with the study requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: 1. Estimated Glomerular Filtration Rate < 20 mL/min/1.73m2 (using the Modification of Diet in Renal Disease [MDRD] formula) 2. Uncontrolled hypertension 3. Uncontrolled ischemic heart disease 4. Uncontrolled clinically significant cardiac arrhythmia 5. Untreated hypo- or hyperthyroidism 6. Prior major organ transplant 7. Known or suspected systemic bacterial, viral, parasitic, or fungal infection 8. Seropositive for hepatitis B virus, hepatitis C virus (HCV) or known to be human immunodeficiency virus positive 9. Received an investigational agent other than tafamidis, diflunisal, doxycycline, or tauroursodeoxycholic acid, or an investigational device within 30 days prior to first dose of study drug 10. Discontinued ALN-TTRSC-002 study due to a treatment-related AE 11. Metastatic cancer within the past 5 years 12. Any conditions which, in the opinion of the Investigator, would make the patient unsuitable for enrollment or could interfere with the patient’s participation in, or completion of, the study 13. History of allergic reaction to an oligonucleotide or GalNAc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of long-term dosing with ALN-TTRSC; Secondary Objective: To assess the PD effect of long-term dosing of ALN-TTRSC on serum levels of TTR. To assess the clinical effects of long-term dosing of ALN-TTRSC, including effect on mortality, hospitalization, and 6-MWT. ; Primary end point(s): Safety and tolerability of long-term dosing of ALN-TTRSC, including: • Assessment of AEs • Clinical laboratory safety tests (hematology, serum chemistry including liver function tests [LFTs], thyroid function, coagulation, and urinalysis) • Vital sign measurements (blood pressure, pulse rate, oral body temperature, and respiratory rate) • 12-Lead ECG • Physical examinations • Eye examinations ; Timepoint(s) of evaluation of this end point: • AEs will be collected throughout the study. • Safety evaluations will be performed as part of Screening and approximately every 12 weeks during the treatment period with the exception of eye examinations, which will be performed once a year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To assess the PD effect of long-term dosing of ALN-TTRSC on serum levels of TTR. • To assess the clinical effects of long-term dosing of ALN-TTRSC, including effect on mortality, hospitalization, and 6-MWT ; Timepoint(s) of evaluation of this end point: • Pharmacodynamic (PD) evaluation will include serial measurement of serum levels of TTR at specified time points. Serum levels of vitamin A will also be evaluated as a secondary PD biomarker. • Evaluations of clinical efficacy will be performed as part of Screening and approximately every 24 weeks during the treatment period | — |
Countries
Canada, United Kingdom, United States
Contacts
Public ContactFaisal Zaman, Clinical Trial Mngr.
Medpace, UK
Outcome results
None listed