Clinical trial NCT01437059: Trial to Evaluate Safety and Tolerability of ALN-PCS02 in Subjects With Elevated LDL-Cholesterol (LDL-C)
Official title: A Phase 1, Randomized, Single-blind, Placebo-Controlled, Single Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of ALN-PCS02 in Subjects With Elevated LDL-Cholesterol (LDL-C)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Elevated LDL-Cholesterol (LDL-C)
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-09-20
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_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-PCS02 in subjects with Elevated LDL-Cholesterol (LDL-C).


Eligibility criteria: Inclusion Criteria:

* Elevated LDL-C of \>3.0 mmol/L and \<5.7 mmol/L
* Fasting triglyceride concentration ≤2.8 mmol/L
* Body weight \>60.0 kg; body mass index (BMI) between 19.00 kg/m2 and \<35.00 kg/m2
* Adequate blood counts, liver and renal function
* May not received any lipid lowering drug/agent within the 30 days prior to the screening
* Non-smokers for at least 3 months
* Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must use an adequate method of birth control
* Males agree to use appropriate contraception
* Willing and able to comply with protocol-required visit schedule and visit requirements and provide written informed consent

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;
* Received megadose vitamin therapy or dietary supplements within 4 weeks prior to screening
* 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-PCS02 (Cmax, tmax, t1/2, AUC0-last, CL).
timeFrame: Up to 180 days
measure: Effect of ALN-PCS02 on Circulating PCSK9 Levels (Determination of % Lowering of PCSK9 to pretreatment/Baseline PCSK9 Level).
timeFrame: Up to 28 days
measure: Effect of ALN-PCS02 on Circulating LDL-c Levels (Determination of % Lowering of LDL-c to pretreatment/Baseline LDL-c Level).
timeFrame: Up to 28 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: Amy Simon, MD
role: STUDY_DIRECTOR
References:
citation: Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, Hutabarat RM, Clausen VA, Karsten V, Cehelsky J, Nochur SV, Kotelianski V, Horton J, Mant T, Chiesa J, Ritter J, Munisamy M, Vaishnaw AK, Gollob JA, Simon A. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet. 2014 Jan 4;383(9911):60-68. doi: 10.1016/S0140-6736(13)61914-5. Epub 2013 Oct 3.