Emory University announced its Vaccine Treatment and Evaluation Unit (VTEU) will help spearhead an NIH-sponsored global clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adult patients combating COVID-19—the first drug to be tested in Gilead’s remdesivir.
The Emory VTEU was activated March 11, 2020, by the National Institute of Allergy and Infectious Diseases (NIAID), meaning it can commence enrolling patients as part of this phase III therapeutic clinical trial reports Emory University in a press release.
What is a VTEU?
NIAID reports Vaccine Treatment and Evaluation Units (VTEUs) have played a key role in NIAID’s efforts to develop new and improved vaccines and therapies against infectious diseases for nearly 50 years. Through this program, NIAID has conducted hundreds of clinical trials, many of which have contributed to vaccine licensure. Importantly, VTEUs have the ability to enroll large numbers of trial volunteers and vaccinate them in a safe, effective, and quick manner. Thus, this program represents a vitally important program for the testing of vaccines for the COVID-19 crisis. Emory is one of eight VTEU’s around the country participating in this COVID-19 Trial.
The VTEUs are a component of the Infectious Diseases Clinical Research Consortium (IDCRC). The IDCRC principal investigators include David S. Stephens—MD, professor, and chair of the Department of Medicine in Emory University School of Medicine and vice president for research of Emory’s Woodruff Health Sciences Center, as well as Kathy Neuzil, MD, and Myron M. Levine—Professor in Vaccinology and director, Center for Vaccine Development, University of Maryland, Baltimore.
The Emory VTEU includes the Hope Clinic of the Emory Vaccine Center and the Emory Children’s Center Vaccine Research Clinic, both renowned in clinical and translational research in infectious diseases vaccines, treatment, and prevention.
Sponsored by the NIH, the study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adult patients diagnosed with COVID-19. A multicenter trial will involve up to 75 research sites worldwide.
The study will include two-arm comparisons between different investigational therapeutic agents and a placebo; Interim monitoring introduces new arms offering flexibility to deal with the need to stop early, futility, efficacy, or safety issues. For example, if one therapy proves to be efficacious (e.g., it is working), this triggers a change, and that treatment becomes the control arm for comparison(s) with new experimental treatment(s).
Patients are stratified by 1) site, and 2) severity of illness at enrollment—severe disease (requiring mechanical ventilation or oxygen, a SpO2 </= 94% or tachypnea (respiratory rate >/= 24 breaths/min)) or mild-moderate disease (SpO2 > 94% and respiratory rate < 24 breaths/min without supplemental oxygen). Subjects (COVID-19 patients) are assessed daily while hospitalized. Discharged patients are thereafter requested to attend study visits at Days 15 and 29. Moreover, all study participants undergo a series of efficacy, safety, and laboratory assessments. The key to this study—evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19.
A Dynamic Situation
These adaptive studies help the sponsor (NIH) and sites (e.g., Emory et al.) deal with unfolding, dynamic situations such as the current COVID-19 crisis. For example, if research teams find that background standards of supportive care improve over time as more is learned about the successful management of COVID-19, then comparisons of safety and efficacy are based on data from concurrently randomized participants.
Active DSMB Monitoring
An independent data and safety monitoring board (DSMB) actively monitors interim data to generate recommendations concerning early study closure or changes to study arms.
The NIH lead for this clinical trial is Dr. Aneesh Mehta, an investigator at both the national VTEU network and National Ebola Training and Education Center (NETEC). The Emory VTEU is led by Nadine Rouphael, Evan Anderson, and Carlos Del Rio. Dr. Mehta reports, “This important study will allow our patients to access the highest-level clinical care, driven by the best data from around the world while contributing to the science of caring for patients with COVID-19.
What is the IDCRC?
The Infectious Diseases Clinical Research Consortium (IDCRC) was formed in 2019 to support the planning and implementation of infectious diseases clinical research that efficiently addresses the scientific priorities of NIAID. It consists of 9 VTEUs and the IDCRC Leadership Group. The IDCRC includes infectious disease leaders and clinical researchers from Emory University, University of Maryland School of Medicine, Johns Hopkins University, Vanderbilt University Medical Center, Baylor College of Medicine, University of Washington, the University of Alabama at Birmingham, Cincinnati Children’s Hospital Medical Center, FHI360, Fred Hutchinson Cancer Research Center, Kaiser Permanente Washington Health Research Institute, University of Rochester, Saint Louis University and the NIH NIAID Division of Microbiology and Infectious Diseases.
Lead Research/Investigators from Emory University
Amish Mehta, MD, Affiliate Faculty, Emory Vaccine Center, Associate Professor, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine
Nadine Rouphael, MD, Affiliate Faculty, Emory Vaccine Center
Evan Anderson, MD Associate Professor, Emory School of Medicine
Carlos Del Rio, MD, Professor & Chair, Hubert Department of Global Health, Rollins School of Public Health; Professor, Department of Medicine, Division of Infectious Diseases