The Cardiovascular Inflammation Reduction Trial (CIRT) Investigator and Coordinator Teleconference October 30, 2014 Elaine Zaharris CIRT Project Manager Aruna Pradhan, MD, MPH Assistant Professor of Medicine Harvard Medical School Director, Preventive Medicine Cohorts Biorepository Brigham and Women’s Hospital, Boston MA 7/24/2014

Agenda for Call Recruitment Overview – Elaine Zaharris Acknowledging Drug Receipt Subject Withdrawals Upcoming Protocol Amendment Q and A 10/30/2014 2

Recruitment Overview Sites Participants 459 interested 393 with IRB approval 369 ready to screen 295 with 1+ participants screened 230 with 1+ participants randomized Participants 2637 with informed consent 2555 screened 1123 randomized (as of October 29, 2014) 10/30/2014 3

Women and Minority Recruitment Total Women Minority Screened 2540 606 733 Percent (%) 100 23.9 28.9 Total Women Minority Randomized 1106 230 270 Percent (%) 100 20.8 24.4 Data as of 10/24/14 10/30/2014

Agenda for Call Recruitment Overview – Elaine Zaharris Acknowledging Drug Receipt Subject Withdrawals Upcoming Protocol Amendment Q and A 10/30/2014 5

Acknowledging Drug Receipt Necessary for dispensing randomization drug packs Site Initiation or Study Drug Resupply RANDOMIZATION CAPABILITY EDC Updated with Pack Numbers and Availability at Study Site FAX Back Acknowledgement FORM to 1) Catalent 2) CIRT CC Drug Shipment from Catalent Drug Arrival at Study Site 10/30/2014

“Shipment Request & Acknowledgement Form” Pre-filled, Site-Specific Completed By Site FAX TO BOTH #s Arrives in the Box

Agenda for Call Recruitment Overview – Elaine Zaharris Acknowledging Drug Receipt Subject Withdrawals Upcoming Protocol Amendment Q and A 10/30/2014 8

Subject Withdrawals Some Definitions: Withdrawal = subject withdraws consent Passive Follow-Up = permanent stop (as with subjects having a confirmed primary EP) Active Follow-Up = in study on drug 10/30/2014

Subject Withdrawals NO REASON FOR IT!! Goal is to keep subjects in active follow-up on study drug. When any and all attempts fail, then passive follow-up with continued completion of study visits. Subject withdrawal (consent withdrawal) should never happen at your site! If a subject at your site has withdrawn, we ask that you approach them for reinstatement in the trial. We will assist with EDC modification to facilitate this. 10/30/2014

Subject Withdrawals: Examples Mrs. S does not feel she can comply with blood draw schedule. Connect with her Remind her that after the first six months, blood draw frequency declines to bimonthly Remind her of the science behind the study and of the importance of her contributions Remind her that blood testing is precautionary Remind her that she can go to a PSC for most draws at her own convenience 10/30/2014

Subject Withdrawals: Examples Mr. M develops a primary endpoint. This results in a permanent stop BUT NOT subject withdrawal from the trial Mr. M should be reinstated in the trial (we will help you with how to do this operationally) He should be retained in passive follow-up 10/30/2014

Agenda for Call Recruitment Overview – Elaine Zaharris Acknowledging Drug Receipt Subject Withdrawals Upcoming Protocol Amendment Q and A 10/30/2014 13

Upcoming Protocol Amendment Qualifying event will be expanded to include ANY PAST history of documented myocardial infarction or multi-vessel coronary artery disease No recency qualifier. 10/30/2014

Qualifying Event: New Eligibility Criteria Documented past history of myocardial infarction Documented past angiographic evidence of multi-vessel coronary artery disease (stent, bypass graft, or angiographic lesion of > 60% in 2 major epicardial vessels or > 50% isolated left main stenosis) 10/30/2014

What documentation is required? Myocardial infarction Hospital discharge record Current EKG with Q waves in 2 contiguous leads Echo with scar or clear wall motion abnormality Nuclear stress test showing scar or wall motion abnormality Angiographic evidence of multivessel CAD Cardiac catheterization report Operative report (PCI or CABG) Not Accepted: Coronary CTA AS BEFORE BUT: NO TIME LIMIT 10/30/2014

Protocol Amendments Protocol Amendment BWH IRB CCC DSMB Copernicus Local IRBs IRB Services EDC System Recruitment Materials Manual of Operations Quick Reference Card 10/30/2014

Protocol Amendments Protocol Amendment BWH IRB CCC DSMB Copernicus Local IRBs IRB Services EDC System Recruitment Materials Manual of Operations Quick Reference Card 10/30/2014

Agenda for Call Recruitment Overview – Elaine Zaharris Acknowledging Drug Receipt Subject Withdrawals Upcoming Protocol Amendment Q and A 10/30/2014 19

Next Coordinator Call November 20, 2014 at 12pm Eastern Thank you for your attention! 10/30/2014