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

Paroxysmal Atrial Fibrillation Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01710852
• Other study ID #: ISIS 329993-CS6
• Status: Completed
• Phase: Phase 2
• First received: October 9, 2012
• Last updated: August 24, 2015
• Start date: October 2012
• Est. completion date: April 2014

Study information

• Verified date: August 2015
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Paroxysmal Atrial Fibrillation

Intervention

Drug:
• ISIS CRP Rx

• Placebo

Locations

Country	Name	City	State
United Kingdom	Eastbourne General Hospital - Cardiology Department	Eastbourne	East Sussex

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AF burden reduction	Burden measured as percentage of time spent in AF as derived from continuous pacemaker monitoring	113 Days	No
Secondary	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	No
Secondary	To assess the effect of ISIS CRP Rx on ventricular rate during sinus rhythm		113 Days	No
Secondary	To assess the effect of ISIS CRP Rx on measures of Quality of Life		113 Days	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No