Trial to Evaluate Safety and Tolerability of ALN-PCS02 in Subjects With Elevated LDL-Cholesterol (LDL-C)

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)

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).

Study Overview

• Status: Completed
• Conditions: Elevated LDL-Cholesterol (LDL-C)
• Intervention / Treatment: Drug: Sterile Normal Saline (0.9% NaCl); Drug: ALN-PCS02

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Clinical Site
  • London, United Kingdom, SE1 1YR
    • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sterile Normal Saline (0.9% NaCl)	Drug: Sterile Normal Saline (0.9% NaCl); Calculated volume to match active comparator
Active Comparator: ALN-PCS02	Drug: ALN-PCS02; Dose levels between 15 and 400 μg/kg by intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK) of ALN-PCS02 (Cmax, tmax, t1/2, AUC0-last, CL).	Up to 180 days
Effect of ALN-PCS02 on Circulating PCSK9 Levels (Determination of % Lowering of PCSK9 to pretreatment/Baseline PCSK9 Level).	Up to 28 days
Effect of ALN-PCS02 on Circulating LDL-c Levels (Determination of % Lowering of LDL-c to pretreatment/Baseline LDL-c Level).	Up to 28 days

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Investigators: Study Director: Amy Simon, MD, Alnylam Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: September 19, 2011
• First Posted (Estimate): September 20, 2011

Study Record Updates

• Last Update Posted (Estimate): October 12, 2012
• Last Update Submitted That Met QC Criteria: October 11, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Other Study ID Numbers: ALN-PCS02-001