Phase 2 Study to Evaluate ALN-TTRSC (Revusiran) in Patients With Transthyretin (TTR) Cardiac Amyloidosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the pharmacokinetics, pharmacodynamics and exploratory clinical activity of ALN-TTRSC (revusiran) in Patients with Transthyretin (TTR) Cardiac Amyloidosis.

Official Title
-----------------
A Phase 2, Open-Label Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Exploratory Clinical Activity of ALN-TTRSC in Patients With Transthyretin (TTR) Cardiac Amyloidosis

Conditions
-----------------
TTR-mediated Amyloidosis

Intervention / Treatment
-----------------
* Drug: ALN-TTRSC (revusiran) for subcutaneous administration


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: TTR cardiac amyloidosis; Women of child-bearing potential (WOCBP) must have a negative pregnancy test, cannot be breast feeding, and must be willing to use 2 highly effective methods of contraception; Male subjects agree to use appropriate contraception; Adequate blood counts, liver, renal and heart function; Adequate Karnofsky performance status; Adequate New York Heart Association (NYHA) Classification Score; Clinically stable on heart medications; Adequate 6-minute walk test; Willing to give written informed consent and are willing to comply with the study requirements. Exclusion Criteria: Known human immunodeficiency virus (HIV) positive status or known or suspected systemic bacterial, viral, parasitic, or fungal infection; Subjects with a history of multiple drug allergies or intolerance to SC injection; 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; Uncontrolled hypertension, ischemic heart disease or cardiac arrhythmia; Untreated hypo- or hyperthyroidism; Prior major organ transplant; Considered unfit for the study by the Principal Investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALN-TTRSC (revusiran)<br> | Drug: ALN-TTRSC (revusiran) for subcutaneous administration<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation. |  | Up to 63 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ALN-TTRSC (revusiran) (Cmax, tmax, t1/2, AUC, CL, Vss, Vz) |  | Up to 90 days | 
| Effect of ALN-TTRSC (revusiran) on transthyretin (TTR) (Determination of % Lowering of TTR to pretreatment/Baseline Levels) |  | Up to 90 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RNAi therapeutic