September 11, 2020 | NSAIDS are safe for COVID-19 patients, a CHOP study shows convalescent plasma appears safe and possibly effective for children, a Boston study shows very low rates of hospital transmission of COVID-19. Plus, NIH launches two Phase 3 trials for blood thinners, the International Vaccine Institute preps with Gates money, and Phesi warns that many clinical trial sites may not bounce back.

Research Updates

Researchers at the University of Southern Denmark, Aarhus University Hospital, and the Danish Medicines Agency, investigated the safety of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19 patients. Contrary to earlier fears, they found use of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2. Their findings were published in PLOS Medicine. DOI: 10.1371/journal.pmed.1003308

Early findings from researchers at Children's Hospital of Philadelphia (CHOP) show that convalescent plasma appears to be a safe and possibly effective treatment for children with life-threatening cases of COVID-19 according to a study published in Pediatric Blood and Cancer. Clinicians treated four critically ill children, 14-18 years old, actively infected with SARS‐CoV‐2 with CP under emergency Investigational New Drug applications (eINDs) through the Food and Drug Administration (FDA). No patients experienced any treatment‐emergent adverse events related to CP infusion. One patient died, two remain on intubation and ventilatory support, and one had an excellent response. We found CP was safe and possibly efficacious, the authors wrote. Randomized pediatric trials are needed. DOI: 10.1002/pbc.28693

A Brigham and Women’s team has tracked the rate of nosocomial COVID-19 transmission in their own hospital over a 12-week period. Of 8,370 patients with non-COVID-19 hospitalizations, 11 tested positive within 14 days of admission. Only one case was deemed hospital-acquired. The analysis reveals that a multifaceted infection control program based on US Centers for Disease Control and Prevention guidance may be associated with minimized risk of nosocomial transmission of SARS-CoV-2 infection, the authors note. They published their results in JAMA. DOI: 10.1001/jamanetworkopen.2020.20498.

Results from two early-phase Russian non-randomized vaccine trials (Sputnik V) in a total of 76 people were published in The Lancet, finding that two formulations of a two-part vaccine have a good safety profile with no serious adverse events detected over 42 days, and induce antibody responses in all participants within 21 days. The trials took place in two hospitals in Russia. DOI: 10.1016/S0140-6736(20)31866-3

Researchers at Children's National Hospital compared the clinical features of 315 pediatric patients who tested positive with COVID-19 between March and May 2020 to a cohort of 1,402 pediatric patients who tested positive for Flu A or B between October 2019 and June 2020 and reported their findings in JAMA Open Network. The researchers found no statistically significant differences in the rates of hospitalization, admission to the intensive care unit and mechanical ventilator use between the two groups. Of the COVID-19 patients, 17% required hospitalization including 6% who required admission to the intensive care unit (ICU) and 3% who subsequently underwent mechanical ventilator treatment. In the flu cohort, 21% were hospitalized including 7% admitted to the ICU and 2% requiring mechanical ventilator support. More patients with COVID-19 than those with flu reported fever, cough, diarrhea or vomiting, headache, body ache or chest pain at the time of diagnosis. DOI: 10.1001/jamanetworkopen.2020.20495.

Industry Updates

The National Institutes of Health has launched two of three adaptive Phase 3 clinical trials evaluating the safety and effectiveness of varying types of blood thinners to treat adults diagnosed with COVID-19. Part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, these trials will be conducted at more than 100 sites around the world and will involve patients in various clinical settings—those who have not been hospitalized, those currently hospitalized and those discharged after hospitalization for moderate to severe disease. Collectively known as ACTIV-4 Antithrombotics, the trials will provide critical insights that could help guide the care of patients with COVID-19, particularly those who suffer from life-threatening blood clots. The trial for hospitalized COVID-19 patients and the trial for patients with COVID-19 who have not been hospitalized are now underway. A third trial to start later will focus on patients discharged after hospitalization for moderate to severe COVID-19 disease. All three clinical trials will be coordinated and overseen by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, and funded through Operation Warp Speed. Press release.

The International Vaccine Institute (IVI) has announced that the Bill & Melinda Gates Foundation awarded close to $1.5M to IVI to support clinical trial site preparedness in four African and Asian countries to potentially support future COVID-19 Phase III efficacy vaccine trials. Following successful completion of early-stage clinical trials of COVID-19 vaccine candidates, it will be essential to transition to efficacy trials at different sites around the world with high disease burden, including those in resource-limited settings. To ensure these sites are prepared for efficacy trials with the necessary technical capability, trained staff, sufficient trial participants, and a thorough assessment of prevailing COVID-19 burden, IVI aims to bolster in-country capacity at select sites by the fourth quarter of 2020. Press release.

New September analysis from Phesi shows the impact of COVID-19 on clinical development is continuing to mount, with many clinical trial sites unable to bounce back following suspension in March and April 2020. Phesi’s previous analysis in May 2020 found that of 300,000 global clinical trial sites, there had been a 38 per cent increase in suspensions from the beginning of the year. Now, data indicate these suspensions peaked in early June, and after an initial drop, have risen again—with over 28,000 sites currently suspended. Sites did begin recruiting again in June 2020, rising to almost pre-pandemic levels. But the analysis shows that while new sites have appeared, many other investigator sites could go under forever. The sudden increase in recruiting sites is likely due to sponsors scrambling to mitigate the impact of COVID-19 and blindly adding new sites, without analyzing via systematical root cause analysis how well their trials were doing in the first place before the pandemic struck. One important note is that this initial analysis can’t show all the variables, because many sponsors and CROs are yet to release COVID-19 data. Press release. 

Diffusion Pharmaceuticals has announced dosing of the first two patients in the company’s open-label Phase 1b lead-in trial of its novel, oxygen-enhancing therapeutic, trans sodium crocetinate (TSC), in 24 hospitalized COVID-19 patients. In addition to evaluating the safety and tolerability of TSC, this trial will collect preliminary data on TSC’s effects on arterial blood oxygenation. The Company believes these pharmacodynamic data will provide proof of concept for TSC in hypoxemic patients, and these data will be used to guide design of the planned follow-on efficacy study. The Phase 1b study is being conducted at the Romanian National Institute of Infectious Diseases. The planned follow-on efficacy trial will be a randomized, placebo-controlled safety and efficacy study of TSC in hospitalized COVID-19 patients that will be conducted in the United States and Europe after consultation with, and approval from, local regulatory authorities. Press release.

The University of Chicago Medicine is launching the BLAZE-1 trial, recruiting 22 participants to be treated with the LY-CoV555 antibody developed by Eli Lilly and Company in collaboration with AbCellera. The antibody was first identified by scientists at the National Institute of Allergy and Infectious Diseases and AbCellera in a blood sample from a U.S. patient who had recovered from COVID-19. The neutralizing monoclonal antibody targets and binds to the spike protein on the surface of the SARS-CoV-2 virus, preventing it from attaching and entering into human cells. Without access to cells, the virus can't replicate. Press release.

Vanderbilt University Medical Center (VUMC) researchers are conducting a clinical trial to determine whether nasal saline irrigations can reduce viral shedding and symptoms in patients with COVID-19. Prior studies have shown that using simple, over-the-counter nasal saline irrigations can decrease viral shedding in upper respiratory infections—including other coronaviruses—helping patients feel better, resolving symptoms in less time and potentially reducing transmissibility of the virus. The trial is already close to meeting its enrollment goal of more than 100 participants with COVID-19. Press release.