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

Primary Purpose

Paroxysmal Atrial Fibrillation

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
ISIS CRP Rx
Placebo
Sponsored by
Ionis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Atrial Fibrillation focused on measuring Atrial Fibrillation, Paroxysmal Atrial Fibrillation, AF

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Eastbourne General Hospital - Cardiology Department

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A

Group B

Arm Description

ISIS CRP Rx followed by Placebo

Placebo followed by ISIS CRP Rx

Outcomes

Primary Outcome Measures

AF burden reduction
Burden measured as percentage of time spent in AF as derived from continuous pacemaker monitoring

Secondary Outcome Measures

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
To assess the effect of ISIS CRP Rx on ventricular rate during sinus rhythm
To assess the effect of ISIS CRP Rx on measures of Quality of Life
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
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.
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.
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

Full Information

First Posted
October 9, 2012
Last Updated
August 24, 2015
Sponsor
Ionis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01710852
Brief Title
Antiarrhythmic and Symptomatic Effect of ISIS CRP Rx Targeting CRP in Paroxysmal Atrial Fibrillation
Acronym
ASET
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Atrial Fibrillation
Keywords
Atrial Fibrillation, Paroxysmal Atrial Fibrillation, AF

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
ISIS CRP Rx followed by Placebo
Arm Title
Group B
Arm Type
Experimental
Arm Description
Placebo followed by ISIS CRP Rx
Intervention Type
Drug
Intervention Name(s)
ISIS CRP Rx
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
AF burden reduction
Description
Burden measured as percentage of time spent in AF as derived from continuous pacemaker monitoring
Time Frame
113 Days
Secondary Outcome Measure Information:
Title
To assess the effect of ISIS CRP Rx on the:
Description
total number of AF episodes average duration of AF per episode average sinus rhythm duration atrial and ventricular rate during AF episodes
Time Frame
113 Days
Title
To assess the effect of ISIS CRP Rx on ventricular rate during sinus rhythm
Time Frame
113 Days
Title
To assess the effect of ISIS CRP Rx on measures of Quality of Life
Time Frame
113 Days
Title
To assess whether treatment with ISIS CRP Rx reduces hsCRP in subjects with paroxysmal AF
Description
Change from Baseline will be compared for each treatment period
Time Frame
113 Days
Title
To assess the safety of ISIS CRP Rx in subjects with paroxysmal AF
Description
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.
Time Frame
113 Days
Title
To assess the tolerability of ISIS CRP Rx in subjects with paroxysmal AF
Description
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.
Time Frame
113 Days
Title
To assess the pharmacokinetics of ISIS CRP Rx in subjects with paroxysmal AF
Description
Trough levels of ISIS CRP Rx will be assessed at intervals throughout the study
Time Frame
113 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Eastbourne General Hospital - Cardiology Department
City
Eastbourne
State/Province
East Sussex
ZIP/Postal Code
BN21 2UD
Country
United Kingdom

12. IPD Sharing Statement

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

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