Antiarrhythmic and Symptomatic Effect of ISIS CRP Rx Targeting CRP in Paroxysmal Atrial Fibrillation (ASET)

A Phase 2 Study to Assess the Antiarrhythmic and Symptomatic Effect of the Second Generation Antisense Oligonucleotide ISIS 329993 Targeting CRP in Patients With Paroxysmal Atrial Fibrillation

The purpose of this study is to evaluate whether treatment with ISIS CRP Rx can reduce AF (Atrial Fibrillation) burden (percentage of time spent in AF) in subjects with paroxysmal AF

Study Overview

• Status: Completed
• Conditions: Paroxysmal Atrial Fibrillation
• Intervention / Treatment: Drug: Placebo; Drug: ISIS CRP Rx

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • East Sussex
    • Eastbourne, East Sussex, United Kingdom, BN21 2UD
      • Eastbourne General Hospital - Cardiology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male of female; age over 18 years
• Dual chamber permanent pacemaker implanted
• Confirmed diagnosis of paroxysmal atrial fibrillation with an AF burden of 1 to 50%, as derived from pacemaker diagnostic algorithms
• Able to have pacemaker antiarrhythmic algorithms turned off for the duration of the study
• Able to discontinue all Class I and III antiarrhythmic medication for the duration of the study
• Therapeutically anticoagulated with warfarin or dabigatran, and anticipated to be for duration of the study
• High sensitivity C-Reactive Protein (hsCRP) between 2 and 10 mg/L (inclusive)

Exclusion Criteria:

• Clinically significant abnormalities in medical history, physical examination, or screening laboratory results that would render a subject unsuitable for inclusion
• NYHA class III/IV heart failure
• Impaired left ventricular function of less than 45% determined by echocardiography within 3 months of screening
• Moderate or greater mitral regurgitation assessed by echocardiography within 3 months of screening
• Permanent AF
• Continuous Amiodarone therapy within 90 days prior to Study Day 1
• Treatment with another Study Drug, biological agent, or device within one-month of screening, or five half-lives of study agent, whichever is longer
• Use of systemic corticosteroids or other anti-inflammatory medications including non-steroidal anti-inflammatory drugs (NSAIDs)
• Use of statins, ACE inhibitors or AT-receptor antagonists unless on a stable regimen for at least 3 months prior to dosing and will remain on a stable regimen for the duration of the study
• Uncontrolled hypertension (BP >160/100)
• Current or expected use of any anticoagulant apart from warfarin or dabigatran

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; ISIS CRP Rx followed by Placebo	Drug: Placebo; Drug: ISIS CRP Rx
Experimental: Group B; Placebo followed by ISIS CRP Rx	Drug: Placebo; Drug: ISIS CRP Rx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AF burden reduction	Burden measured as percentage of time spent in AF as derived from continuous pacemaker monitoring	113 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect of ISIS CRP Rx on the:	total number of AF episodes; average duration of AF per episode; average sinus rhythm duration; atrial and ventricular rate during AF episodes	113 Days
To assess the effect of ISIS CRP Rx on ventricular rate during sinus rhythm		113 Days
To assess the effect of ISIS CRP Rx on measures of Quality of Life		113 Days
To assess whether treatment with ISIS CRP Rx reduces hsCRP in subjects with paroxysmal AF	Change from Baseline will be compared for each treatment period	113 Days
To assess the safety of ISIS CRP Rx in subjects with paroxysmal AF	Incidence rates of all Adverse Events will be tabulated by MedRA system Organ Class and by MedRA Term for each treatment group. Lab Tests, Vital Signs, And ECG Parameters will be summarized by study visit for each treatment group.	113 Days
To assess the tolerability of ISIS CRP Rx in subjects with paroxysmal AF	Incidence rates of all Adverse Events will be tabulated by MedRA system Organ Class and by MedRA Term for each treatment group. Lab Tests, Vital Signs, And ECG Parameters will be summarized by study visit for each treatment group.	113 Days
To assess the pharmacokinetics of ISIS CRP Rx in subjects with paroxysmal AF	Trough levels of ISIS CRP Rx will be assessed at intervals throughout the study	113 Days

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 9, 2012
• First Submitted That Met QC Criteria: October 17, 2012
• First Posted (Estimate): October 19, 2012

Study Record Updates

• Last Update Posted (Estimate): August 26, 2015
• Last Update Submitted That Met QC Criteria: August 24, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; AF; Paroxysmal Atrial Fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: ISIS 329993-CS6