Clinical trial NCT01814839: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: TTR-mediated Amyloidosis
Keywords: RNAi therapeutic
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-03-20
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
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 ALN-TTRSC (revusiran) in healthy volunteer subjects.


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.

Primary outcomes:
measure: The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation.
timeFrame: Up to 63 days
Secondary outcomes:
measure: Pharmacokinetics (PK) of ALN-TTRSC (revusiran) (Cmax, tmax, t1/2, AUC0-last, CL).
timeFrame: Up to 90 days
measure: Effect of ALN-TTRSC (revusiran) on transthyretin (TTR) (Determination of % Lowering of TTR to pretreatment/Baseline Levels).
timeFrame: Up to 90 days
measure: Effect of ALN-TTRSC (revusiran) on vitamin A (Determination of % Lowering of vitamin A to pretreatment/Baseline Levels).
timeFrame: Up to 90 days
measure: Effect of ALN-TTRSC (revusiran) on retinol binding protein (RBP) (Determination of % Lowering of RBP to pretreatment/Baseline Levels).
timeFrame: Up to 90 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: