SISTER Study: Improving Stroke Treatment Response with TS23
SISTER Study led by Eva Mistry aims to identify a safe and effective dose of TS23 for treating ischemic stroke patients with core-penumbra mismatch. The Phase-2 trial involves 300 adults and spans 54 months, with primary endpoints focusing on treatment efficacy and safety. The study is randomized, placebo-controlled, and blinded, emphasizing the importance of optimized stroke treatment strategies.
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SISTER Strategy for Improving Stroke Treatment Response Eva Mistry, MBBS, MSCI, FAHA Associate Professor, University of Cincinnati
SISTER Principal Investigators Eva Mistry, MBBS, MSCI SISTER Protocol PI Pooja Khatri, MD, MSc SISTER Contact PI Guy Reed, MD, MS TS23 Inventor and IND holder Jordan Elm, PhD Statistical PI
SISTER Trial Managers Pam Plummer, MSN, RC, CCRC NCC Project Manager Sarah Bailey, MS Prime Project Manager Aaron Perlmutter, MPH, MSW Site Monitoring Manager Katie Stever, MPH NDMC Data Manager
SISTER Study Timeline Grant Notice of Award (NoA) and 38 sites selected Sites complete CTA & cIRB with 4-6 weeks of receipt MOPPs released to sites Investigator meeting (1/18) Monthly webinars start SISTER Site Kick- off Call Individual site imaging training First participant enrolled IRB and FDA approval obtained PM office hours start Drug shipping 1stDSMB Meeting July- October 2023 Fall 2023 December 2023 January 2024 February 2024 March 2024
SISTER: Study Drug Background Plasmin Plasminogen Alpha-2 Antiplasmin Red Blood Cells tPA/TNK Platelets Fibrin TS23
SISTER: Study Description Phase-2 Prospective Randomized Placebo-controlled Blinded Adaptive Dose Finding
SISTER: Primary Objective To identify a dose of TS23 that is safe and potentially more efficacious than placebo for the treatment of patients from 4.5 to 24 hours of ischemic stroke onset, who have evidence of core- penumbra mismatch on perfusion imaging.
SISTER: Basic Study Information Study Population: Study Duration: 54 Months Study intervention: Participant Duration: 90 days 300 adults ( 18 years) with acute ischemic stroke 4 dosing arms and a control arm
SISTER: Primary Endpoints Safety: Efficacy: ANY intracranial hemorrhage (ICH) visualized on the CT scan 30 ( 6) h after study drug administration. NIH Stroke Scale Score at 30 ( 6) h after study drug administration (adjusted for the baseline in analysis)
SISTER: Secondary Endpoints Clinical Efficacy: BiomarkerEfficacy: 1. a2AP activity at 3 ( 1) h after completion of therapy 1. Improvement in level of global disability (Modified Rankin Scale (mRS) distribution) at 90 ( 7) days. 2. Matrix metalloproteinase-9 (MMP-9) plasma level 3 ( 1) h after completion of therapy. 2. Frequency of excellent functional outcome (mRS 0-1) at 90 ( 7) days. 3. % tissue reperfusion on 30 ( 6) h perfusion scan compared to the baseline 3. National Institutes of Health Stroke Scale (NIHSS) at 72 ( 12) h (or discharge if sooner; adjusted for the baseline in analysis)
Secondary Endpoints Continued Pharmacokinetics & anti-drug antibodies: Safety Endpoints: 1. Incidence of symptomatic ICH within 30 ( 6) h of study drug administration (SITS- MOST definition) 1. Pharmacokinetic (PK) profile of TS23 at 3 (+/-1) h and 30 ( 4) h after completion of therapy and 90 ( 7) days. 2. Incidence of non-ICH major or clinically relevant non-major bleeding within 30 ( 5) days of study drug administration. 2. Evaluation of anti-drug antibodies to TS23 (at baseline and 90 ( 7) d follow-up visit). 3. Non-bleeding, serious adverse events (SAEs) within 90 ( 7) days 4. Incidence of stroke-related and all-cause deaths within 90 ( 7) days 5. Plasma fibrinogen levels at 3 (+/-1) h after completion of study drug administration
SISTER: Study Population 1. 18 years old with anterior circulation acute ischemic stroke 2. NIHSS 6 and are able to receive study drug within 4.5-24 hours after stroke onset (or last known well) 3. Evidence of core-penumbra mismatch on baseline perfusion imaging
SISTER: Key Inclusion Criteria 1. 2. 3. 4. Age 18 years and older Suspected anterior circulation acute ischemic stroke Presenting NIH Stroke Scale score 6 Favorable baseline neuroimaging consisting of all of the following: ASPECTS of 6 or more on CT (or ASPECTS of 7 on MRI Favorable perfusion imaging on CT perfusion (CTP)/MR-perfusion weighted imaging (PWI) consisting of all of the following: Mismatch ratio of penumbra:core >1.2 Mismatch volume >10 cc Core <70 cc Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well. Able to receive assigned study drug within 90 minutes of qualifying perfusion imaging.* 5. 6.
SISTER: Key Exclusion Criteria 1. Received/planned clinical IV thrombolysis/EVT 2. Pre-stroke modified Rankin score (mRS) >2 3. GP IIB/IIIA inhibitors <14 days 4. Positive urine pregnancy test 5. Receiving renal dialysis, regardless of creatinine 6. Other standard alteplase exclusion criteria
SISTER Site PIs and PSCs Site Name Ascension St. John Barnes Jewish Hospital Brigham and Women s Hospital Christiana Hospital Grady Memorial Hospital Harborview Medical Center Houston Methodist Hospital Jackson Memorial Hospital Kaiser Permanente Los Angeles Site Principal Investigator Dr. Rahul Rahangdale Dr. Charles Kircher Dr. Rahula Mahajan Primary Study Coordinator Stacie Merritt Jenny Babka Quinn Rademaker Dr. Jason Nomura Dr. Michael Frankel Dr. David Tirschwell Dr. Vivek Misra Dr. Gillian Gordon-Perue Dr. Navdeep Sangha Rich Baker Alicia Escobar Lauren Klein David McCane Andrea Escobar Vanessa Audea
SISTER Site PIs and PSCs Site Name MHealth Fairview Southdale MHealth Fairview Massachusetts General Hospital Site Principal Investigator Dr. Muhammad Affan Dr. Muhammad Affan Dr. Aneesh Singhal Primary Study Coordinator Julie Scherber Julie Scherber Elaina Hill Mayo Clinic Phoenix MUSC Memorial Hermann Mount Sinai West Mount Sinai Hospital North Shore University Hospital Dr. Rohan Arora Dr. Gyan Kumar Dr. Christine Holmstedt Dr. Andrew Barreto Dr. J Mocco Dr. J Mocco Erica Boyd Caitlan LeMatty Prasen Marella Cynthia Nguyen Cynthia Nguyen Kirendra Pasram
SISTER Site PIs and PSCs Site Name NYP Columbia NYU Langone- Brooklyn OSU Wexner Medical Center PRISMA Upstate Rhode Island Hospital SUNY Upstate Sutter Medical Center Temple University Hospital USCD Health La Jolla Site Principal Investigator Dr. Shivani Ghoshal Dr. Aaron Lord Dr. Jan Bittar Dr. Sanjeev Sivakumar Dr. Farhan Khan Dr. Claribel Wee Dr. Manoj Mittal Dr. Nina Gentile Dr. Royya Modir Primary Study Coordinator Angela Valazquez Maria Cotrina Luke Herren Reilly Leonard Lena Deb Dawn Lenakakis Hannah Reimer Maryo Jajo
SISTER Site PIs and PSCs Site Name USCD Hillcrest Hospital UF Health Shands Hospitals United Hospital University of Chicago University of Cincinnati University of Iowa Hospital University of Utah UNTHSC/Methodist UVA Medical Center Wake Forest Baptist Yale New Haven Hospital Site Principal Investigator Dr. Royya Modir Dr. Amita Singh Dr. Ganesh Asaithambi Dr. Shyam Prabhakaran Dr. Yasmin Aziz Dr. Malik Ghannam Dr. Vivek Reddy Dr. Balaji Krishnaiah Dr. Amna Sohail Dr. Jakita Baldwin Dr. James Giles Primary Study Coordinator Maryo Jajo Amy Holland Maxwell Kaiman Elida Romo Marchelle Nowell-Bostic Heena Olalde Theodore Rock Quentin Thacker Andrew Weko Daniela Castro Castillo Michael Kampp
SISTER Study Timeline Grant Notice of Award (NoA) and 38 sites selected Sites complete CTA & cIRB with 4-6 weeks of receipt MOPPs released to sites Investigator meeting (1/18) Monthly webinars start SISTER Site Kick- off Call Individual site imaging training First participant enrolled IRB and FDA approval obtained PM office hours start Drug shipping 1stDSMB Meeting July- October 2023 Fall 2023 December 2023 January 2024 February 2024 March 2024
sister-trial@ucmail.uc.edu @SisterTrial
