2/2 A Phase 2 Study of Elafin (Tiprelestat) for the Treatment of Pulmonary Arterial Hypertension (PAH) - PROJECT ABSTRACT The ATHENA trial represents a new paradigm to slowing the progression of disease in people with pulmonary arterial hypertension (PAH). With our clinical coordinating center (CCC) collaborators, we propose a phase 2, multi-center, randomized, double-blind, placebo-controlled trial of tiprelestat (recombinant human Elafin) to evaluate its impact on pulmonary vascular resistance (PVR) and safety. Participants will be stratified by baseline PVR and baseline REVEAL Lite 2.0 risk score. The primary endpoint of the study is the change in PVR from baseline to week 24. Our clinical collaborators have successfully demonstrated the safety and tolerability of Elafin in a phase 1 trial of 30 healthy individuals (NCT 03522935), and have assembled a group of clinical sites with experience in PAH and clinical trials. The ATHENA trial will extend their promising pilot data to a formal phase 2 clinical trial among PAH patients. An experienced data coordinating center (DCC) with strong statistical leadership and expertise is key in both design and analysis, particularly when unanticipated issues arise during the conduct of a clinical trial. The University of Michigan (UM) Statistical Analysis of Biomedical and Educational Research (SABER) unit within a top-ranked department of biostatistics will serve as DCC, bringing together an experienced group of faculty and staff in biostatistics, project management, study monitoring, database design and data management, software development, and research administration. SABER has a strong track record of collaborations with a CCC under this funding model. The overarching goal of the UM DCC is to collaborate with study investigators, the CCC, and NHLBI to enable successful achievement of the study on time and within budget. We will accomplish these goals through the three specific aims: (1) Enhance scientific rigor by providing statistical and clinical trials methodological expertise to design, analyze, and disseminate research findings; (2) Ensure the collection of timely, accurate and reproducible data, and maximize adherence to the study protocol; and (3) Provide established infrastructure and services for study administration and operations and for communication among study stakeholders. Our leadership, experience, and expertise will promote collaborations, encourage scientific productivity, and facilitate timely dissemination of findings on the benefits of Elafin in patients living with PAH. We anticipate that upon completion of this proposed study, our data will support the role of Elafin as a safe and efficacious PAH therapy, with the potential to be a disease-modifying agent with therapeutic effects sustained even after the treatment is discontinued. It will inform the design of the Phase 3 pivotal study of this novel PAH therapy.
