Clinical trial NCT01559077: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: TTR-mediated Amyloidosis
Keywords: ATTR
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-03-21
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation.
timeFrame: Up to 28 days
Secondary outcomes:
measure: Pharmacokinetics (PK) of ALN-TTR02 (Cmax, tmax, t1/2, AUC0-last, CL).
timeFrame: Up to 180 days
measure: 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)
timeFrame: Up to 56 days
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Clinical Site
city: London
country: United Kingdom
facility: Clinical Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Jared Gollob, MD
role: STUDY_DIRECTOR
References:
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.