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

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

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

Study Overview

• Status: Completed
• Conditions: TTR-mediated Amyloidosis
• Intervention / Treatment: Drug: ALN-TTRSC (revusiran); Drug: Sterile Normal Saline (0.9% NaCl)

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Clinical Site
  • London, United Kingdom, NW10 7EW
    • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ALN-TTRSC (revusiran)	Drug: ALN-TTRSC (revusiran); Ascending doses of ALN-TTRSC (revusiran) by subcutaneous (SC) injection
Placebo Comparator: Sterile Normal Saline (0.9% NaCl)	Drug: Sterile Normal Saline (0.9% NaCl); Calculated volume to match active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: March 18, 2013
• First Submitted That Met QC Criteria: March 19, 2013
• First Posted (Estimate): March 20, 2013

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: February 4, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: RNAi therapeutic
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: ALN-TTRSC-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No