NCT01437059

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Sep 2011

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2011

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

September 19, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 20, 2011

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2012

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2012

Completed
Last Updated

October 12, 2012

Status Verified

October 1, 2012

Enrollment Period

6 months

First QC Date

September 19, 2011

Last Update Submit

October 11, 2012

Conditions

Elevated LDL-Cholesterol (LDL-C)

Outcome Measures

Primary Outcomes (1)

  • The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation.

    Up to 28 days

Secondary Outcomes (3)

  • 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

Study Arms (2)

ALN-PCS02

ACTIVE COMPARATOR
Drug: ALN-PCS02

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR
Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

ALN-PCS02DRUG

Dose levels between 15 and 400 μg/kg by intravenous (IV) infusion

ALN-PCS02
Sterile Normal Saline (0.9% NaCl)DRUG

Calculated volume to match active comparator

Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Clinical Site

Leeds, LS2 9LH, United Kingdom

Location

Clinical Site

London, SE1 1YR, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 24094767DERIVED

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHyperlipoproteinemiasHyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Amy Simon, MD

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 19, 2011

First Posted

September 20, 2011

Study Start

September 1, 2011

Primary Completion

March 1, 2012

Study Completion

September 1, 2012

Last Updated

October 12, 2012

Record last verified: 2012-10

Locations

GB(2)