Atrial fibrillation (AF) MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: CRP Antisense Oligonucleotide
Product Code: ISIS 329993
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ISIS 329993
Sponsors
Isis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements 2. Males or females aged over 18 years old at the time of informed consent 3. Satisfy the following: a. Females: Non-pregnant and non-lactating; surgically sterile, post-menopausal, abstinent, or if engaged in sexual relations of child-bearing potential, subject is using an acceptable contraceptive method (refer to Section 6.3.1) from the time that the participant informed consent document is signed until 60 days after the last dose of Study Drug b. Males: Surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, subject is utilizing an acceptable contraceptive method (refer to Section 6.3.1) from the time that the participant informed consent document is signed until 60 days after the last dose of Study Drug 4. Dual chamber permanent pacemaker implanted at least 3 months prior to screening 5. Confirmed diagnosis of paroxysmal atrial fibrillation with an AF burden of 1 to 50% at screening, as derived from pacemaker diagnostic algorithms 6. Able to have pacemaker antiarrhythmic algorithms turned off for the duration of the study 7. Able to discontinue all Class I and III antiarrhythmic medication for the duration of the study 8. Therapeutically anticoagulated with Warfarin, and anticipated to be anticoagulated with Warfarin for the duration of the study 9. High sensitivity C-Reactive Protein (hsCRP) =2 mg/L and =10 mg/L at screening (2 measurements taken at least 1 week apart) unless pre-approved by Sponsor Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: 1. Clinically significant abnormalities in medical history (e.g., acute coronary syndrome within six months of screening, major surgery within three months of screening) or physical examination 2. Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion: a) Renal Function: •Urine protein or blood persistently positive by dipstick •Estimated creatinine clearance calculated according to the formula of Cockcroft and Gault 1.5 x ULN •Total bilirubin >ULN c) Hematology: •Platelet count 160/100) 21. History of bleeding diathesis or coagulopathy 22. Current or expected use of any anticoagulant apart from Warfarin 23. Regular use of alcohol within 6 months prior to screening (>7 drinks/week for females, >14 drinks/week for ma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate whether treatment with ISIS 329993 can reduce AF (Atrial Fibrillation) burden (percentage of time spent in AF as derived from continuous pacemaker monitoring) in subjects with paroxysmal AF; Secondary Objective: 1. To assess the effect of ISIS 329993 on the total number of AF (Atrial Fibrillation) episodes, average duration of AF per episode, average sinus rhythm duration, and atrial and ventricular rate during AF episodes derived from continuous pacemaker monitoring. 2. To assess the effect of ISIS 329993 on ventricular rate during sinus rhythm derived from continuous pacemaker monitoring. 3. To assess the effect of ISIS 329993 on PR, QRS, QT and QTc intervals derived from 12-lead ECG during periods of sinus rhythm. 4. To assess the effect of ISIS 329993 on measures of Quality of Life as assessed by SF 36, VAS, EHRA grade and AFSS questionnaires. 5. To assess whether treatment with ISIS 329993 reduces hsCRP in subjects with paroxysmal AF. 6. To assess the safety, tolerability, and pharmacokinetics (PK) of ISIS 329993 in subjects with paroxysmal AF. ;Primary end point(s): AF burden as assessed by the use of long term beat to beat pacemaker Holter monitoring;Timepoint(s) of evaluation of this end point: Day 28 and 56 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Total number of AF episodes, average duration of AF per episode, average sinus rhythm duration and atrial and ventricular rate during AF episodes • Ventricular rate during sinus rhythm • Quality of life measures assessed by SF 36, VAS, EHRA grade and AFSS questionnaires The effects of treatment with ISIS 329993 vs. Placebo on the following pharmacodynamic measures will be evaluated: • hsCRP and other markers of inflammation (for example erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), IL-6, sTNF-R1 and –R2, fibrinogen). ;Timepoint(s) of evaluation of this end point: Day 28 and 56 | — |
Countries
United Kingdom
Contacts
Public ContactMatt Buck
Isis Pharmaceuticals, Inc.
Outcome results
None listed