Trial to Evaluate Safety, Tolerability, and Parmacokinetics of ALN-TTR02 in Healthy Volunteer Subjects
Primary Purpose
TTR-mediated Amyloidosis
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
ALN-TTR02
Sterile Normal Saline (0.9% NaCl)
Sponsored by

About this trial
This is an interventional treatment trial for TTR-mediated Amyloidosis focused on measuring ATTR
Eligibility Criteria
Inclusion Criteria:
- Body mass index must be between 18.0 kg/m2 and ≤ 31.5 kg/m2;
- Non-smokers for at least 3 months preceding screening;
- Females subjects must be of non-childbearing potential e.g., post-menopausal or pre-menopausal with surgical sterilization;
- Males agree to use appropriate contraception;
- Medical history must be verified by either a personal physician or medical practitioner as appropriate;
- Willing to give written informed consent and are willing to comply with the study requirements.
Exclusion Criteria:
- Known hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection
- Multiple drug allergies or know sensitivity to oligonucleotide
- History of drug abuse and/or alcohol abuse
- Receiving an investigational agent within 3 months prior to study drug administration
- Subjects with safety laboratory test results deemed clinical significant by the Investigator;
- Received prescription drugs within 4 weeks of first dosing
- Subjects who have donated more than 500 mL of blood within the 3 months prior to ALN-PCS02 or placebo administration;
- Subjects who have used prescription drugs within 4 weeks of first dosing
- Considered unfit for the study by the Principal Investigator
- Employee or family member of the sponsor or the clinical study site personnel
Sites / Locations
- Clinical Site
- Clinical Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
ALN-TTR02
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-TTR02 (Cmax, tmax, t1/2, AUC0-last, CL).
Effect of ALN-TTR02 on transthyretin (TTR), vitamin A, and retinol binding protein (RBP) (Determination of % Lowering of TTR, vitamin A and RBP to pretreatment/Baseline Levels)
Full Information
NCT ID
NCT01559077
First Posted
March 19, 2012
Last Updated
January 14, 2013
Sponsor
Alnylam Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01559077
Brief Title
Trial to Evaluate Safety, Tolerability, and Parmacokinetics of ALN-TTR02 in Healthy Volunteer Subjects
Official Title
A Phase 1, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of ALN-TTR02 in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
November 2012 (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 a single dose of ALN-TTR02 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
ATTR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ALN-TTR02
Arm Type
Active Comparator
Arm Title
Sterile Normal Saline (0.9% NaCl)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ALN-TTR02
Intervention Description
Dose levels between 0.01 and 0.5 mg/kg by intravenous (IV) infusion
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 28 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of ALN-TTR02 (Cmax, tmax, t1/2, AUC0-last, CL).
Time Frame
Up to 180 days
Title
Effect of ALN-TTR02 on transthyretin (TTR), vitamin A, and retinol binding protein (RBP) (Determination of % Lowering of TTR, vitamin A and RBP to pretreatment/Baseline Levels)
Time Frame
Up to 56 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Body mass index must be between 18.0 kg/m2 and ≤ 31.5 kg/m2;
Non-smokers for at least 3 months preceding screening;
Females subjects must be of non-childbearing potential e.g., post-menopausal or pre-menopausal with surgical sterilization;
Males agree to use appropriate contraception;
Medical history must be verified by either a personal physician or medical practitioner as appropriate;
Willing to give written informed consent and are willing to comply with the study requirements.
Exclusion Criteria:
Known hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection
Multiple drug allergies or know sensitivity to oligonucleotide
History of drug abuse and/or alcohol abuse
Receiving an investigational agent within 3 months prior to study drug administration
Subjects with safety laboratory test results deemed clinical significant by the Investigator;
Received prescription drugs within 4 weeks of first dosing
Subjects who have donated more than 500 mL of blood within the 3 months prior to ALN-PCS02 or placebo administration;
Subjects who have used prescription drugs within 4 weeks of first dosing
Considered unfit for the study by the Principal Investigator
Employee or family member of the sponsor or the clinical study site personnel
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
Citations:
PubMed Identifier
23984729
Citation
Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, Perez J, Chiesa J, Warrington S, Tranter E, Munisamy M, Falzone R, Harrop J, Cehelsky J, Bettencourt BR, Geissler M, Butler JS, Sehgal A, Meyers RE, Chen Q, Borland T, Hutabarat RM, Clausen VA, Alvarez R, Fitzgerald K, Gamba-Vitalo C, Nochur SV, Vaishnaw AK, Sah DW, Gollob JA, Suhr OB. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013 Aug 29;369(9):819-29. doi: 10.1056/NEJMoa1208760.
Results Reference
derived
Learn more about this trial
Trial to Evaluate Safety, Tolerability, and Parmacokinetics of ALN-TTR02 in Healthy Volunteer Subjects
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