NIH begins large clinical trial to test immune modulators for treatment of COVID-19

Press release

Friday, October 16, 2020

The National Institutes of Health has launched an adaptive Phase 3 clinical trial to assess the safety and efficacy of three immune modulator drugs in hospitalized adults with COVID-19. Some patients with COVID-19 undergo an immune response in which the immune system releases excessive amounts of proteins that trigger inflammation – called a “cytokine storm” – which can lead to acute respiratory distress syndrome, multiple organ 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 trial, known as the ACTIV-1 (IM) immune modulators, will determine whether the therapeutics are able to restore balance to an overactive immune system.

As part of the Accelerating Therapeutic Interventions and COVID-19 Vaccines (ACTIV) initiative, the trial plans to recruit approximately 2,100 hospitalized adults with moderate to severe COVID-19 to medical facilities in the United States and Canada. Latin America. The National Center for the Advancement of Translational Sciences (NCATS), part of NIH, will coordinate and oversee the trial with financial support from the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services. social. Preparation and response, in support of the objectives of the Trump administration’s Operation Warp Speed. BARDA’s Clinical Studies Network will be responsible for operationalizing the trial through a task order assigned to the contract research organization Technical Resources International, Inc.

“This is the fifth major protocol to be launched under the ACTIV partnership in an unprecedented time frame, and it is focusing its efforts on the most promising therapies for the treatment of COVID-19,” said the director of NIH , Francis S. Collins, MD, Ph.D. “Immune modulators provide another treatment modality in the ACTIV therapy toolkit to help manage the complex and multisystemic conditions that can be caused by this very serious disease.”

ACTIV-1 IM is a randomized, placebo-controlled trial that uses an adaptive master protocol. One of the characteristics of the main protocols is that they allow a coordinated and efficient evaluation of several investigational agents as they become available. This allows maximum flexibility to quickly eliminate drugs that are not showing efficacy, identify those that do in a short period of time, and quickly incorporate additional investigational agents into the trial.

The public-private partnership ACTIV selected three agents for the study from a pool of over 130 immune modulators initially screened on the basis of several factors, including their relevance to COVID-19, strong evidence for use. against inflammatory response and cytokine storm and availability for large- scale clinical studies. The initial agents are infliximab (REMICADE), developed by Janssen Research & Development, LLC., One of the Janssen pharmaceutical companies of Johnson & Johnson; abatacept (ORENCIA), developed by Bristol Myers Squibb; and Cenicriviroc (CVC), an advanced stage investigational agent developed by AbbVie.

All trial participants will receive remdesivir, which is the current standard treatment for hospital patients with COVID-19. Convalescent plasma and dexamethasone will be permitted at the discretion of the site investigator and according to national guidelines. They will be randomly assigned to receive a placebo or one of the immune modulators as an adjunct. The trial will investigate the different combined treatment regimens with respect to disease severity, speed of recovery, mortality, and use of hospital resources.

Registration is now open and the trial is expected to last around six months. Results will be available soon after the trial ends, or perhaps sooner if analysis conducted during the trial indicates that one or more of the drugs are of benefit. To ensure that the trial is conducted in a safe and efficient manner, an independent Data and Safety Oversight Committee will oversee the trial and conduct periodic reviews of the accumulated data.

The chairman of the protocol team is William G. Powderly, MD, director of the Institute for Clinical and Translational Sciences and co-director of the Division of Infectious Diseases at Washington University School of Medicine in St. Louis. NCATS ‘Clinical and Translational Sciences (CTSA) awards program and the Trial Innovation Network will play a key role in adding study sites in the United States and recruiting patients, including those from affected communities of disproportionately by COVID-19.

“The agility and innovation of the CTSA program in conducting clinical trials, along with the network’s extensive capacity and broad geographic reach, have positioned it to rapidly implement this important trial,” said Christopher P Austin, MD, director of NCATS. “The innovative design of the trial will allow efficient evaluation of three different potential COVID-19 treatments simultaneously, providing possible new treatments to patients more quickly and valuable insights into 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 COVID-19 treatments and vaccines. Coordinated by the National Institutes of Health Foundation, ACTIV brings together partners from government, industry, academia and nonprofit organizations. Visit the ACTIV Therapeutics page.

About HHS, ASPR and BARDA: The HHS strives to improve and protect the health and well-being of all Americans, by providing effective health and human services and by promoting advances in medicine, public health, and social services. ASPR’s mission is to save lives and protect Americans from the health security threats of the 21st century. Within ASPR, BARDA invests in innovation, cutting-edge research and development, acquisition and manufacture of medical countermeasures – vaccines, drugs, therapeutics, diagnostic tools and non-pharmaceuticals necessary for fight against threats to health security. To date, 55 products supported by BARDA have obtained FDA approval, license or clearance. To learn more about BARDA’s development portfolios and the partnership with BARDA, visit medicalcountermeasures.gov. To learn more about federal public health and medical preparedness and response, visit phe.gov.

About the National Center for the Advancement of Translational Sciences (NCATS): NCATS conducts and supports research into the science and how translation – the process by which interventions to improve health are developed and implemented – to enable more treatments to reach more patients, faster . For more information on how NCATS helps shorten the journey from scientific observation to clinical intervention, visit https://ncats.nih.gov.

About the National Institutes of Health (NIH):The NIH, the national agency for medical research, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the principal federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.

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