ZZ-3K3A-201: Safety Evaluation of 3K3A-APC in Ischemic Stroke

Currently, the only approved treatment in the US for ischemic stroke is a drug called recombinant tissue plasminogen activator (rtPA or tPA), indicated for intravenous administration within three hours of onset of the stroke. The drug is designed to break down blood clots to restore blood flow to the brain and thereby prevent further damage. In some patients however, tPA can cause internal bleeding and other complications. 3K3A-APC’s cytoprotective properties may be useful in protecting ischemic brain tissue from further damage, while avoiding an increase in the chance of treatment-related bleeding.

This research study is being conducted to determine the safety, tolerability and activity of 3K3A-APC, following the use of tissue plasminogen activator (tPA) in subjects who have experienced moderately severe acute hemispheric ischemic stroke. The study intervention will be administered as a 15 minute infusion every 12 hours for up to 5 infusions. Four dose levels will be considered for this trial. Approximately 115 participants of age 18-90 years old will be enrolled and followed for 90 days.

Results were presented at the International Stroke Conference in January, 2018 and confirmed that 3K3A-APC appears safe and tolerable, and that a suggestion of vasculoprotection (reduced hemorrhage) requires confirmation in a larger trial.

Patrick D. Lyden, MD, Chairman of the Department of Neurology at Cedars-Sinai Medical Center, is the Protocol Principal Investigator of the study. Kent E. Pryor, PhD, Chief Operating Officer of ZZ Biotech, is the Principal Investigator of the X01 NeuroNEXT Infrastructure Resource Access Award. Berislav V. Zlokovic, MD, PhD, Director of the Zilkha Neurogenetic Institute at Keck School of Medicine, University of Southern California, is the Co-Investigator.

NN104 is supported by NINDS (U01 NS088312).

Protocol Principal Investigator: 
Contact Information: 

CCC Project Managers: Timothy Leonard, Daniela Grasso

DCC Project Coordinators: Julie QidwaiCynthia Diltz

  • Lyden P, Pryor KE, Coffey CS, Cudkowicz M, Conwit R, Jadhav A, Sawyer RN, Claassen J, Adeoye O, Song S, Hannon P, Rost NS, Hinduja A, Torbey M, Lee JM, Benesch C, Rippee M, Rymer M, Froehler MT, Haley EC, Johnson M, Yankey J, Magee K, Qidwai J, Levy H, Haacke EM, Fawaz M, Davis TP, Toga AQ, Griffin JH, Zlokovic BV, the NeuroNEXT Clinical Trials Network NN104 Investigators Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant Human Activated Protein C, in Combination with Tissue Plasminogen Activ... Annals of Neurology201985125-136.

  • Lyden P, Weymer S, Coffey C, Cudkowicz M, Berg S, O'Brien S, Fisher M, Haley EC, Khatri P, Saver J, Levine S, Levy H, Rymer M, Wechsler L, Jadhav A, McNeil E, Waddy S, Pryor K. Selecting patients for intraarterial therapy in the context of a clinical trial for neuroprotection. Stroke201647(12)2979-2985.
    PubMed: PMC5134840