A Study of the Safety, Tolerability and Pharmacokinetics of ALN-TTR02 in Japanese Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of patisiran (ALN-TTR02) in Japanese subjects

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

Conditions
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Transthyretin (TTR)-Mediated Amyloidosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese adult males and females aged 20 to 65 years, inclusive (The subject was born in Japan and has lived outside of Japan for <10 years, and subject's biological parents and grandparents are fully Japanese and were born in Japan); Subjects who are healthy as determined by clinical assessments; Females subjects must be of non-childbearing potential; Males with partners of child-bearing potential, must agree to use appropriate contraception. Exclusion Criteria: Subjects with a history of serious mental illness; Subjects who have a clinically relevant medical or surgical history; Subjects with a positive screen for alcohol or drugs of abuse; Subjects with safety laboratory test results deemed clinically significant; Subjects with known hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection; Subjects who have received an investigational agent within the 3 months prior to study entry.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: patisiran (ALN-TTR02)<br> | Drug: patisiran (ALN-TTR02)<br>* Ascending doses administered by intravenous (IV) infusion<br>|
| Active 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?
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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 |
| --- | --- | --- |
| Pharmacodynamics (PD) of ALN-TTR02 (serum concentrations of Transthyretin, Vitamin A, and Retinol Binding Protein) |  | Up to 90 days | 
| Observed maximum concentration (Cmax) of ALN-TTR02 |  | Up to 90 days | 
| Time of observed maximum concentration (tmax) of ALN-TTR02 |  | Up to 90 days | 
| Area under the plasma concentration versus time curve (AUC) of ALN-TTR02 |  | Up to 90 days | 
| Terminal elimination half-life (t1/2) of ALN-TTR02 |  | Up to 90 days | 
| Systemic clearance (CL) of ALN-TTR02 |  | Up to 90 days | 
| Volume of distribution (V) of ALN-TTR02 |  | Up to 90 days | 
| Renal clearance (CLR) of ALN-TTR02 |  | Up to 90 days | 

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