Transthyretin mediated amyloidosis (ATTR) MedDRA version: 15.1 Level: PT Classification code 10007509 Term: Cardiac amyloidosis System Organ Class: 10007541 - Cardiac disorders MedDRA version: 15.1 Level: PT Classification code 10019889 Term: Hereditary neuropathic amyloidosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Alnylam Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18 years or older. 2. Patients has a biopsy-proven diagnosis of TTR amyloidosis with documented signs/symptoms of the disease (e.g., sensory, motor, or autonomic neuropathy) that are at least mild to moderate in severity. 3. Body mass index (BMI) of 17–33 kg/m2. 4. Karnofsky performance status of 60% or greater. 5. Absolute neutrophil count (ANC) =1500 cells/mm³, platelet count =100,000 cells/mm³, and hemoglobin =10 g/dL. 6. Adequate liver function, demonstrated by an aspartate transaminase (AST) and alanine transaminase (ALT) =2.5 x the upper limit of normal (ULN), total bilirubin within normal limits, albumin >3 g/dL, international normalized ratio (INR) =1.2. 7. Adequate renal function: serum creatinine =1.5 x ULN. 8. Seronegative for hepatitis B virus (HBV) and hepatitis C virus (HCV). 9. Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be using two highly effective methods of contraception ( hormonal - oral, implantable, injectable, or transdermal contraceptives in conjunction with spermicide, condom, or diaphragm; mechanical - spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine device (IUD) in conjunction with spermicide or condom; or surgical sterilization of partner in conjunction with spermicide, condom, or diaphragm) prior to screening, throughout study participation, and for 1 month after ending study participation. 10. Males agree to use appropriate contraception throughout study participation and for 1 month after ending study participation. 11. Patient is willing and able to comply with protocol required visit schedule and visit requirements and provide written informed consent. 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 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Pregnant or nursing. 2. Has had a liver transplant. 3. Has a known surgery planned during any point of the study period. 4. Has known human immunodeficiency virus (HIV) positive status. 5. Has a known or suspected systemic bacterial, viral, parasitic, or fungal infection. 6. Received an investigational agent, other than tafamidis or diflunisal, within 30 days prior to study drug administration. 7. Has a New York Heart Association heart failure classification >2. 8. Has unstable angina. 9. Has uncontrolled clinically significant cardiac arrhythmia. 10. Is considered unfit for the study by the Principal Investigator. 11. Had a prior severe reaction to a liposomal product. 12. Has known hypersensitivity to oligonucleotides. 13. Is an employee or family member of Alnylam, the CRO, or the clinical study site personnel.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the safety and tolerability of multiple doses of ALN-TTR02.;Secondary Objective: • To characterize the plasma and urine PK of ALN-TTR02. • To assess preliminary evidence of the PD effect of ALN-TTR02 on serum total TTR levels.;Primary end point(s): To evaluate the safety and tolerability of multiple doses of ALN-TTR02 including: •assessment of adverse events (AEs), •12 lead electrocardiograms (ECGs), • cardiac monitoring (telemetry) •arterial oxygen saturation (SaO2) using pulse oximetry, •vital signs (blood pressure, pulse rate, oral body temperature and respiratory rate), •clinical laboratory safety tests (hematology, serum chemistry, coagulation, urinalysis, liver function, lipid panel, thyroid function, complement factor Bb, cytokines, and •physical examinations.;Timepoint(s) of evaluation of this end point: The review of AEs will be done at each visit from Day 0 through Day 56. The other assessments will be carried out at specific timepoints between screening and D208, as described in the study schedule. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PK profile of ALN-TTR02, including: •plasma-concentration time profiles for ALN-18328 and the novel lipid components DLin-MC3-DMA and PEG2000-C-DMG. PD effect of ALN-TTR02 on serum TTR, RBP and Vitamin A, including: •serial assessment of serum concentrations of TTR, TTR mRNA, RBP and Vitamin A.;Timepoint(s) of evaluation of this end point: ALN-18328, PEG2000-C-DMG and DLin-MC3-DMA concentrations will be determined at specified time points between D0 and D208, as described in the study schedule. An assessment of the concentrations of serum TTR, TTR mRNA, RBP and Vitamin A will be determined at specified time points between screening and D208, as described in the study schedule. | — |
Countries
Brazil, France, Germany, Portugal, Spain, Sweden
Contacts
Public ContactClinical Trials Information
Medpace Finland OY
Outcome results
None listed