April 17, 2020 | The clinical research community continues to aggressively research and innovate for SARS-CoV-2 solutions. The latest this week includes many COVID-19 trials, patient registries, PPE exchanges, and much more.

Literature Updates

Researchers at the University of Pittsburgh School of Medicine have launched a study that is being integrated with the electronic health record system at UPMC to fast-track the testing of the anti-malarial drug hydroxychloroquine, steroids and immunomodulators. It uses an adaptive clinical trial model that relies reinforcement learning, a type of artificial intelligence, to identify the best therapy for COVID-19 faster than the traditional scientific approach. The novel REMAP (randomized, embedded, multi-factorial, adaptive platform) employed, and described in an article published in the Annals of the American Thoracic Society, was originally intended to find optimal treatments for severe pneumonia. The REMAP design is a flexible version of adaptive platform trials endorsed by the U.S. Food and Drug Administration. The trial design uses a machine learning model incorporating data from enrollees around the world to continuously learn which therapies and therapy combinations are performing best. Nearly all patients will receive one or more active therapies specifically targeting COVID-19 within weeks. DOI: 10.1513/AnnalsATS.202003-192SD

A new Traditional, Complementary and Integrative Health and Medicine (TCIHM) COVID-19 Support Registry, housed at the Helfgott Research Institute (Portland, Oregon), aims to capture key information on the treatment, supportive care and outcome variables related to the use of integrative health products and practices in COVID-19 patients. Details about the Registry published in JACM, The Journal of Alternative and Complementary Medicine. The registry is already backed by over a dozen practitioner organizations. Non-biomedical strategies against COVID-19 are widely used in some countries, including India and China, while governments in the West are silent or antagonistic despite experimentation by millions of their citizens. DOI: 10.1089/acm.2020.29083.jjw

Researchers at UC San Diego Health have produced the first empirical evidence strongly associating loss of smell and taste with COVID-19 infections. Their study findings, published in the International Forum of Allergy & Rhinology, suggest clinicians should include sensory impairment as a standard screening measure. The loss of smell and taste was typically profound but, encouragingly, with a high recovery rate usually within two to four weeks of infection. Sensory return typically matched the timing of disease recovery. Interestingly, researchers found that patients reporting a sore throat more often tested negative for COVID-19. DOI: 10.1002/alr.22579

Meanwhile, in a review published in Laryngoscope Investigative Otolaryngology, a University of Cincinnati ear, nose and throat specialist concludes that loss of smell could be an early indicator of a COVID-19 infection. COVID-19 is not associated with symptoms typical of a viral cold, such as nasal blockage or mucus production, and the distinction is what makes it easy to distinguish the novel coronavirus from seasonal allergies. When loss of smell occurs as an initial symptom it is particularly instructive. Press release.

An endocrinologist at University of Miami Miller School of Medicine suggests DPP4 inhibitors could help patients who have mild or moderate COVID-19 with type 2 diabetes and clinical trials should be considered. DPP4 is an enzyme that, while only partially understood, is known to play significant roles in inflammatory responses and insulin regulation. DPP4 inhibitors increase insulin and GLP-1 secretion and are commonly prescribed for people suffering from type 2 diabetes. Data from Wuhan and Italy have shown type 2 diabetes patients with the coronavirus have higher mortality and ICU admission rates. The commentary posted in Diabetes Research and Clinical Practice. Press release.

In a small group of patients hospitalized with severe complications of COVID-19 treated with remdesivir, 68% experienced clinical improvement, according to an analysis co-authored by an epidemiologist at Cedars-Sinai Medical Center and published in The New England Journal of Medicine. The experimental therapy was given to patients through the FDA’s compassionate use program. Data on 53 patients in the U.S., Europe, Canada and Japan who received at least one dose of remdesivir by March 7 were evaluated and the effort was led by Gilead Sciences, the drug’s manufacturer. Cedars-Sinai continues to explore remdesivir as a therapeutic option for patients as part of a large international randomized controlled study sponsored by the NIH. DOI: 10.1016/j.diabres.2020.108125

A consortium of medical research organizations known as NETwork is investigating whether overactive immune cells that produce neutrophil extracellular traps (NETs) cause the most severe cases of COVID-19. Collaborators include Cold Spring Harbor Laboratory, the Feinstein Institutes for Medical Research, Research Institute of the McGill University Health Centre, Weill Cornell Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Centre Hospitalier Universitaire de Nancy, University of Michigan, University of California, San Francisco, University of Texas MD Anderson Cancer Center, University of Utah School of Medicine, and Northwell Health. In a paper published in the Journal of Experimental Medicine, researchers point to clear similarities between clinical presentation of severe COVID-19 and other known diseases driven by NETs, such as ARDS, and the importance of determining the presence of NETs in samples from patients that are associated with disease severity and/or particular clinical characteristics of COVID-19. NETwork institution researchers are now pursuing studies into whether NETs are a common feature in COVID-19 cases. If their theory proves correct, treatments used for other NET and neutrophil-driven diseases such as cystic fibrosis, gout and rheumatoid arthritis may be deployed. DOI: 10.1084/jem.20200652

Exercise may prevent or reduce the severity of acute respiratory distress syndrome (ARDS), a deadly complication of COVID-19, and help explain why approximately 80% of confirmed COVID-19 patients have mild symptoms with no need of respiratory support, according to a top exercise researcher at the University of Virginia Health System. In a review published in Redox Biology, the authors report findings about a powerful and protective antioxidant known as extracellular superoxide dismutase (EcSOD) that is naturally produced by the muscles and has prompted development of a novel therapeutic for ARDS caused by COVID-19. Research in mice suggests that blocking the production of EcSOD worsens heart problems, while increasing it has a beneficial effect. A decrease in EcSOD is also associated with chronic conditions such as osteoarthritis. It is thought that even a single session of exercise increases production of the antioxidant, meaning people should find ways to exercise even while maintaining social distancing. DOI: 10.1016/j.redox.2020.101508

Industry News

Cytel has launched an open-access global COVID-19 Clinical Trial Tracker to help facilitate greater collaboration between researchers, policymakers, clinicians, journalists, philanthropists, and other critical stakeholders who need to understand the complex dynamics of the global response to finding a solution to the COVID-19 outbreak. Funded in part by The Bill and Melinda Gates Foundation, the live dashboard offers an overview of all the trials taking place in the international effort to tackle the pandemic. This will enable them to make more informed and pragmatic decisions on how to channel scarce resources. Clinicians and local government need to know what trials are taking place in their community to ensure that the right patients receive the right exploratory treatment, while philanthropists and Federal policymakers deserve a one-stop shop to determine which are the most promising early phase treatment results. More information.

Eagle Pharmaceuticals, a New Jersey-based pharmaceutical company, announced that its product RYANODEX (dantrolene sodium) for injectable suspension inhibited the growth of SARS-CoV-2, the virus causing the COVID-19 pandemic, in a controlled in vitro laboratory test. On Tuesday, April 14, Eagle submitted its Investigational New Drug application to the U.S. Food and Drug Administration for a Phase 2 clinical trial in partnership with Hackensack University Medical Center to evaluate the efficacy of RYANODEX in patients infected with SARS-CoV-2. In the meantime, Eagle is working to increase production of RYANODEX in advance of clinical results and to potentially shorten the supply chain lead time if necessary. Press release.

Sera Labs and Terratori Technologies have created an online exchange to connect frontline medical professionals and administrators with the lowest-cost FDA-approved Personal Protective Equipment (PPE) suppliers. Bringing together a team of military veterans, import/export professionals and technologists, the groups are creating a transparent marketplace that matches high demand needs to high-quality providers will enable the expedient delivery of products to those who need them most. On Terratori’s site, members gain access to a real-time needs assessment map, offering total situational awareness of supply & demand decision points, to provide the most effective and cost-managed process possible. More information.

Accelerated Enrollment Solutions (AES), a business of PPD, has launched a new program to help biopharmaceutical companies maintain business continuity during the global COVID-19 pandemic by transferring clinical trial patients to AES’ dedicated research sites from other research facilities impacted by the coronavirus crisis. As academic and hospital-based sites turn their attention to the front-line care of COVID-19 patients, biopharmaceutical companies face the prospect of delaying or canceling clinical trials. AES’ patient-transfer program is designed to address this issue through its global site organization, which includes dedicated research sites committed exclusively to clinical research. With more than 180 research locations in 17 countries, AES has a broad global footprint that can support the transfer of patients, which ultimately depends on the sites’ proximity to the patients and their ability to support the trial protocol. Press release.

First Databank (FDB) is offering authoritative drug- and medical device-related information about novel coronavirus (COVID-19) on its website for healthcare professionals and consumers at no cost. As a service to healthcare professionals, FDB has launched dedicated COVID-19 drug and medical device resource pages on its website. The drug information related to COVID-19 focuses on three medications currently being tested for use by clinicians to treat the virus: remdesivir, chloroquine, and hydroxychloroquine. The medical device information from FDB—curated from the company’s FDB Prizm medical device knowledge platform and other available sources—includes an extensive list of manufacturers and vendors of COVID-19-related supplies such as ventilators, N95 masks, gloves, and other personal protective equipment. Part numbers and unique device identifier (UDI) information from FDB’s exclusive databases are included, as well as each manufacturer’s contact information. Press release.

Inato has unveiled its anticovid platform, a comprehensive, central repository for all existing clinical trials for SARS-CoV 2 (the virus responsible for COVID-19). The anticovid platform is public, free to access and offers extensive search and filtering capabilities—a unique and critical feature given the unprecedented pace at which COVID-19 clinical trial research is evolving. The purpose of Inato’s anticovid platform is to provide the global healthcare community with easy and efficient access to any available COVID-19 trial information and research trends. The anticovid platform analyzes the latest COVID-19 clinical trial information, providing platform subscribers new analysis twice per week. Most recently, the platform deduced that: nearly 1,000 COVID-19 trials were launched or anticipated in the past 4 months; while China remains responsible for the most trials, Italy, France and the U.S. have significantly grown their contributions in recent weeks; early signals suggest some antiviral agents could be ineffective for treating COVID-19 (at least in seriously ill patients), however a significant focus of trials remains on those drugs. Chloroquine/hydroxychloroquine is also a focus, with more than 50,000 participants currently participating in this therapeutic class of trials in the U.S. More information.

A cell therapy clinical trial launched for patients with severe COVID-19 at the University of Miami Health System and Jackson Health System. The study will enroll 24 patients and test the safety and exploratory efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSC) to block life-threatening lung inflammation. The Cure Alliance is sponsoring the initiative, and the clinical protocol has been shared with academic institutions worldwide who want to test similar treatment strategies. The FDA, which granted immediate authorization for the trial to begin, previously allowed the testing of UC-MSC cell products in patients with type 1 diabetes and Alzheimer's disease at the University of Miami as part of other clinical trials. Press release.

It took researchers at University of Utah Health and Intermountain Healthcare only two weeks to launch a pair of trials to test the effectiveness and safety of hydroxychloroquine and azithromycin (an antibiotic typically used for sinusitis or pneumonia) in treating patients with COVID-19. The first trial, which expects to enroll 300 patients, will randomize to one drug or the other. In the second trial, an anticipated 2,000 patients with confirmed COVID-19 being treated as outpatients will be given one drug or the other—and monitored via telehealth—to see if either can prevent hospitalization. The trials will also determine whether hydroxychloroquine impacts viral shedding and prevents infection of household contacts compared to placebo. Press release.

Meanwhile, Washington University School of Medicine in St. Louis announced it is launching a clinical trial testing different combinations of the antimalarial drugs chloroquine and hydroxychloroquine and azithromycin for patients hospitalized with COVID-19 at Barnes-Jewish Hospital. Express Scripts is donating the medications. The goal is to determine if any of these drugs, alone or in combination, decreases the severity or duration of respiratory symptoms. Only patients ill enough to be admitted to the hospital are eligible, with an expected 500 enrolling over the course of the study. Press release.

ERA-EDTA, one of the world’s largest nephrology associations, has created a European database collecting data on individual dialysis and transplant patients with COVID-19 to measure outcomes and define risk factors. The rationale is conflicting reports suggesting patients on dialysis or with a kidney transplant have limited symptomatology. The experiences of Spanish patients on dialysis, who are particularly frail and old, also may not represent the dialysis population of other countries where organ transplantation rates are lower. Nephrologists across Europe are being invited to submit their patients’ data. Press release.

Wake Forest Baptist Health has joined forces with clinical research organization Javara Inc. and Oracle to launch a community-based COVID-19 study of the novel coronavirus. The study’s goal is to improve understanding of the pandemic and regional infection patterns so strategies and treatments can be developed to contain and possibly eliminate the virus in defined communities. It will employ at-home rapid diagnostic kits as well as a web-based Patient Monitoring System to collect daily information across a large population of participants. Atrium Health and MedStar Health are the first healthcare systems to join the project, which will eventually extend nationwide. Press release.

Temple University Hospital reports that it has treated its first patient in U.S. in the BREATHE clinical trial evaluating the impact of intravenous treatment with gimsilumab on mortality for patients with COVID-19 and ARDS. Gimsilumab is a fully human monoclonal antibody targeting granulocyte macrophage-colony stimulating factor, which is believed to be a key driver of lung hyper-inflammation. It has been tested in numerous non-clinical studies and two prior clinical studies, including a phase 1 study that completed dosing in February and has demonstrated a favorable safety and tolerability profile based on data collected to date. The adaptive, randomized, double-blind, placebo-controlled pivotal trial is sponsored by Roivant Sciences and will enroll up to 270 patients at multiple sites. The primary endpoint is incidence of mortality by day 43; key secondary endpoints include the incidence and duration of mechanical ventilation use during the study, number of days in the intensive care unit, and number of days of inpatient hospitalization. Press release.

A new clinical trial led by the University of Warwick and Queen's University Belfast seeks to find alternatives to ventilators to treat patients who are critically ill with COVID-19. The RECOVERY-RS Respiratory Support trial will compare standard care, intubation and invasive ventilation with other non-invasive treatment methods such as masks driven by oxygen or high-flow oxygen through the nose. Approximately 4,000 adult patients in NHS hospitals with suspected or confirmed COVID-19 will be recruited, and which treatment they receive will be decided by a computer at random. Researchers theorize that non-invasive interventions at an earlier stage may reduce the need for invasive ventilation with a mechanical ventilator. While such treatments are already available and have been used for patients with COVID-19, it is not known which approach is the most effective. Press release.

Synapse Biomedical, a spinoff company from University Hospitals Cleveland Medical Center (UH) and Case Western Reserve University, has received FDA approval for emergency use of its TransAeris Diaphragmatic Pacing (DP) Stimulator System to help wean COVID-19 patients off of the ventilator. The technology could reduce the amount of time COVID-19 patients spend on ventilators by 26 percent. It functions with temporary small electrodes implanted by minimally invasive surgery to stimulate the diaphragm. One of the earliest versions of DP was used by the late actor Christopher Reeve of Superman fame. UH was the first site in the U.S. where DP helped cardiac patients get off ventilators. Press release.