Trial to Evaluate Safety, Tolerability, and Parmacokinetics of ALN-TTR02 in Healthy Volunteer Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of a single dose of ALN-TTR02 in healthy volunteer subjects.

Official Title
-----------------
A Phase 1, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of ALN-TTR02 in Healthy Volunteers

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

Intervention / Treatment
-----------------
* Drug: ALN-TTR02
* Drug: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index must be between 18.0 kg/m2 and ≤ 31.5 kg/m2; Non-smokers for at least 3 months preceding screening; Females subjects must be of non-childbearing potential e.g., post-menopausal or pre-menopausal with surgical sterilization; Males agree to use appropriate contraception; Medical history must be verified by either a personal physician or medical practitioner as appropriate; Willing to give written informed consent and are willing to comply with the study requirements. Exclusion Criteria: Known hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection Multiple drug allergies or know sensitivity to oligonucleotide History of drug abuse and/or alcohol abuse Receiving an investigational agent within 3 months prior to study drug administration Subjects with safety laboratory test results deemed clinical significant by the Investigator; Received prescription drugs within 4 weeks of first dosing Subjects who have donated more than 500 mL of blood within the 3 months prior to ALN-PCS02 or placebo administration; Subjects who have used prescription drugs within 4 weeks of first dosing Considered unfit for the study by the Principal Investigator Employee or family member of the sponsor or the clinical study site personnel

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALN-TTR02<br> | Drug: ALN-TTR02<br>* Dose levels between 0.01 and 0.5 mg/kg by intravenous (IV) infusion<br>|
| Placebo Comparator: Sterile Normal Saline (0.9% NaCl)<br> | Drug: Sterile Normal Saline (0.9% NaCl)<br>* Calculated volume to match active comparator<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 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ALN-TTR02 (Cmax, tmax, t1/2, AUC0-last, CL). |  | Up to 180 days | 
| Effect of ALN-TTR02 on transthyretin (TTR), vitamin A, and retinol binding protein (RBP) (Determination of % Lowering of TTR, vitamin A and RBP to pretreatment/Baseline Levels) |  | Up to 56 days | 

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