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

TTR-mediated Amyloidosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01814839
• Other study ID #: ALN-TTRSC-001
• Status: Completed
• Phase: Phase 1
• First received: March 18, 2013
• Last updated: February 4, 2016
• Start date: March 2013
• Est. completion date: May 2015

Study information

• Verified date: February 2016
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: May 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyloidosis
• TTR-mediated Amyloidosis

Intervention

Drug:
• ALN-TTRSC (revusiran)
Ascending doses of ALN-TTRSC (revusiran) by subcutaneous (SC) injection
• Sterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator

Locations

Country	Name	City	State
United Kingdom	Clinical Site	Leeds
United Kingdom	Clinical Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation.		Up to 63 days	Yes
Secondary	Pharmacokinetics (PK) of ALN-TTRSC (revusiran) (Cmax, tmax, t1/2, AUC0-last, CL).		Up to 90 days	No
Secondary	Effect of ALN-TTRSC (revusiran) on transthyretin (TTR) (Determination of % Lowering of TTR to pretreatment/Baseline Levels).		Up to 90 days	No
Secondary	Effect of ALN-TTRSC (revusiran) on vitamin A (Determination of % Lowering of vitamin A to pretreatment/Baseline Levels).		Up to 90 days	No
Secondary	Effect of ALN-TTRSC (revusiran) on retinol binding protein (RBP) (Determination of % Lowering of RBP to pretreatment/Baseline Levels).		Up to 90 days	No