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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

Primary Purpose

TTR-mediated Amyloidosis

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
ALN-TTRSC (revusiran)
Sterile Normal Saline (0.9% NaCl)
Sponsored by
Alnylam Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for TTR-mediated Amyloidosis focused on measuring RNAi therapeutic

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Clinical Site
  • Clinical Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

ALN-TTRSC (revusiran)

Sterile Normal Saline (0.9% NaCl)

Arm Description

Outcomes

Primary Outcome Measures

The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation.

Secondary Outcome Measures

Pharmacokinetics (PK) of ALN-TTRSC (revusiran) (Cmax, tmax, t1/2, AUC0-last, CL).
Effect of ALN-TTRSC (revusiran) on transthyretin (TTR) (Determination of % Lowering of TTR to pretreatment/Baseline Levels).
Effect of ALN-TTRSC (revusiran) on vitamin A (Determination of % Lowering of vitamin A to pretreatment/Baseline Levels).
Effect of ALN-TTRSC (revusiran) on retinol binding protein (RBP) (Determination of % Lowering of RBP to pretreatment/Baseline Levels).

Full Information

First Posted
March 18, 2013
Last Updated
February 4, 2016
Sponsor
Alnylam Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01814839
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
TTR-mediated Amyloidosis
Keywords
RNAi therapeutic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
85 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ALN-TTRSC (revusiran)
Arm Type
Active Comparator
Arm Title
Sterile Normal Saline (0.9% NaCl)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ALN-TTRSC (revusiran)
Intervention Description
Ascending doses of ALN-TTRSC (revusiran) by subcutaneous (SC) injection
Intervention Type
Drug
Intervention Name(s)
Sterile Normal Saline (0.9% NaCl)
Intervention Description
Calculated volume to match active comparator
Primary Outcome Measure Information:
Title
The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation.
Time Frame
Up to 63 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of ALN-TTRSC (revusiran) (Cmax, tmax, t1/2, AUC0-last, CL).
Time Frame
Up to 90 days
Title
Effect of ALN-TTRSC (revusiran) on transthyretin (TTR) (Determination of % Lowering of TTR to pretreatment/Baseline Levels).
Time Frame
Up to 90 days
Title
Effect of ALN-TTRSC (revusiran) on vitamin A (Determination of % Lowering of vitamin A to pretreatment/Baseline Levels).
Time Frame
Up to 90 days
Title
Effect of ALN-TTRSC (revusiran) on retinol binding protein (RBP) (Determination of % Lowering of RBP to pretreatment/Baseline Levels).
Time Frame
Up to 90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jared Gollob, MD
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Site
City
Leeds
ZIP/Postal Code
LS2 9LH
Country
United Kingdom
Facility Name
Clinical Site
City
London
ZIP/Postal Code
NW10 7EW
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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