A Phase 1, Single- and Multi-Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-TTRSC (Revusiran) in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-TTRSC (revusiran) in healthy volunteer subjects.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Single- and Multi-Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-TTRSC in Healthy Volunteers

Conditions
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TTR-mediated Amyloidosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) must be ≥ 16.5 kg/m2 and ≤ 35.0 kg/m2; Female subjects must be of non-childbearing potential; e.g., postmenopausal or pre-menopausal with surgical sterilization; Male subjects agree to use appropriate contraception; Adequate blood counts, liver and renal function; Non-smokers for at least 3 months; Willing to give written informed consent and are willing to comply with the study requirements; 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 (cohorts 19 and 20). 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; History of drug abuse and/or alcohol abuse; Receiving an investigational agent within 3 months prior to study drug administration; Considered unfit for the study by the Principal Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALN-TTRSC (revusiran)<br> | Drug: ALN-TTRSC (revusiran)<br>* Ascending doses of ALN-TTRSC (revusiran) by subcutaneous (SC) injection<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?
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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 63 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ALN-TTRSC (revusiran) (Cmax, tmax, t1/2, AUC0-last, CL). |  | 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 | 
| Effect of ALN-TTRSC (revusiran) on vitamin A (Determination of % Lowering of vitamin A to pretreatment/Baseline Levels). |  | Up to 90 days | 
| Effect of ALN-TTRSC (revusiran) on retinol binding protein (RBP) (Determination of % Lowering of RBP to pretreatment/Baseline Levels). |  | 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