Friday, October 16, 2020
The National Institutes of Health has launched a phase 3 adaptive clinical trial to evaluate the safety and efficacy of three immune modulator drugs in hospitalized adults with COVID-19. Some patients with COVID-19 experience an immune response in which the immune system releases excessive amounts of proteins that cause inflammation – called a ‘cytokine storm’ – which can lead to acute respiratory distress syndrome, multiorgan failure and other life-threatening complications. The clinical trial aims to determine whether modulating this immune response can reduce the need for ventilators and shorten hospital stays. The test, known as ACTIV-1
As part of the COVID-19 Therapy and Vaccine Acceleration Initiative (ACTIV), the study expects to include approximately 2,100 hospitalized adults with moderate to severe COVID-19 in hospitals in the United States and Latin America. The National Center for the Development of Translational Sciences (NCATS), part of the NIH, will coordinate and monitor the study with financial support from the Biomedical Research and Development Authority (BARDA) of the US Department of Health and Human Services Assistant Secretary for Readiness and response, in support of the goals of the Trump administration’s Warp Speed operation. BARDA’s Clinical Trials Network will be responsible for the operational conduct of the trial by commissioning a task assigned to the research organization Technical Resources International, Inc.
“This is the fifth major protocol launched within the ACTIV partnership in an unprecedented timeframe and focuses efforts on the therapies that have the greatest promise for the treatment of COVID-19,” said NIH Director Francis C. Collins, Ph.D. -р. “Immune modulators provide another treatment in the ACTIV therapeutic toolkit that helps manage the complex, multisystem conditions that can be caused by this very serious disease.”
ACTIV-1 IM is a randomized, placebo-controlled study that uses an adaptive master protocol. One of the hallmarks of the main protocols is that they allow for a coordinated and effective assessment of multiple investigative agents when they become available. This allows maximum flexibility for the rapid elimination of drugs that do not demonstrate efficacy, for the identification of those that do so in a short period of time, and for the rapid inclusion of additional experimental agents in the trial.
The ACTIV Public-Private Partnership selected three agents for the study from a group of more than 130 immune modulators initially reviewed based on several factors, including their relevance to COVID-19, strong evidence for use against inflammatory response and cytokine storm, and availability for large-scale clinical researches. The original agents were infliximab (REMICADE), developed by Janssen Research & Development, LLC., One of Janssen’s pharmaceutical companies at Johnson & Johnson; abatacept (ORENCIA), developed by Bristol Myers Squibb; and Cenicriviroc (CVC), a late-stage test agent developed by AbbVie.
All study participants will receive remdezivir, which is the current standard for the treatment of hospitalized patients with COVID-19. Convalescent plasma and dexamethasone will be permitted at the discretion of the site investigator and in accordance with national guidelines. They will be randomized to receive a placebo or one of the immune modulators as an adjunct treatment. The study will examine the different combination treatment regimens in terms of disease severity, recovery rate, mortality and use of hospital resources.
Registration is now open and the process is expected to take approximately six months. The results will be available soon after the study is completed or possibly earlier if the analysis performed during the study shows that one or more of the drugs are useful. To ensure that the test is conducted in a safe and effective manner, an independent data and safety monitoring board will monitor the test and periodically review the cumulative data.
The protocol team is chaired by Dr. William G. Powderley, director of the Institute of Clinical and Translational Sciences and co-director of the Department of Infectious Diseases at the St. Louis School of Medicine in Washington. The NCATS Clinical and Translational Science Awards Program (CTSA) and the Trial Innovation Network will play a key role in adding research sites in the United States and enrolling patients, including those from communities disproportionately affected by COVID-19.
“The agility and innovation of the CTSA program in conducting clinical trials – together with the extensive network capacity and wide geographical scope – have positioned it for the rapid implementation of this important study,” said NCATS Director Christopher Austin, PhD, “Innovative Study Design.” will allow the effective evaluation of three different potential COVID-19 treatments simultaneously, providing faster new possible treatments for patients and valuable information on the science of clinical translation. “
The NIH announced the ACTIV initiative in April 2020 to develop a national research response to prioritize and accelerate the development of the most promising treatments and vaccines against COVID-19. Coordinated by the Foundation for National Health Institutes, ACTIV brings together partners from government, industry, academia and non-profit organizations. Visit the ACTIV Therapeutics page.
Regarding HHS, ASPR and BARDA: HHS works to improve and protect the health and well-being of all Americans by providing effective health and human services and promoting advances in medicine, public health, and social services. ASPR’s mission is to save lives and protect Americans from 21st century health threats. Within ASPR, BARDA invests in innovation, advanced research and development, acquisition and production of medical countermeasures – vaccines, drugs, therapeutic agents, diagnostic tools and non-pharmaceutical products needed to combat health security threats. To date, 55 products supported by BARDA have received FDA approval, licensing or approval. For more information on BARDA’s development portfolio and partnership with BARDA, visit medicalcountermeasures.gov. To learn more about federal public health and medical preparedness and response, visit phe.gov.
For the National Center for the Development of Translational Sciences (NCATS): NCATS conducts and supports research in the field of science and translation operations, the process by which health improvement interventions are developed and implemented to allow more treatments to reach more patients more quickly. For more information on how NCATS helps shorten the journey from scientific observation to clinical intervention, visit https://ncats.nih.gov.
For National Institutes of Health (NIH):
The NIH, the National Agency for Medical Research, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the main federal agency that conducts and supports basic, clinical, and translational medical research and investigates the causes, treatment, and treatment of both common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.
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