July 31, 2020 | Groups of researchers are raising red flags about the quality of COVID-19 clinical trials. A group from Stanford and Yale warned that studies may not be well designed to contribute meaningful clinical evidence. Another group from Johns Hopkins cautioned against overstepping ethical bounds in public health surveillance. Meanwhile, many new trials are launched.  

Literature Updates

We must be very careful to differentiate public health activities classified as surveillance from those that constitute research. Both are necessary in a pandemic for understanding disease epidemiology and transmission, but defining activities as public health surveillance has profound implications, because there is then no further ethical oversight, no legal requirement in the United States for informed consent, and no specific protection for vulnerable participants or communities. So warns a team of bioethicists from Johns Hopkins University in a paper in the Annals of Internal Medicine. We believe the use of the Common Rule exclusion of public health surveillance activities from research protections amid this pandemic does not justify unlimited research activities without consent, they write. Data and specimens may be collected, tested, and even stored for legitimate public health surveillance, but their use for subsequent research is not exempt from regulations governing human subjects research. DOI: 10.7326/M20-4631 

A Chinese team observed a cohort of 124 patients with COVID-19 and found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, the authors identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes for the severely ill patients in comparison to the control patients. They published their findings in Acta Pharmaceutica Sinica B. DOI: 10.1016/j.apsb.2020.04.008

Researchers from Stanford and Yale raised red flags on the strength of COVID-19 trials recently registered on ClinicalTrials.gov. They published their concerns at JAMA Internal Medicine in a research letter. The team scoured ClinicalTrials.gov and identified 1,551 studies registered from March 1, 2011, to May 19, 2020. They excluded any studies that were canceled. They found that 58.7% of the trials were interventional and 41.3% were observational. 76.1% were single-center trials. Only 11.3% were placebo-controlled and blinded with at least 2 study centers. The authors urge institutional review boards to work with investigators to ensure that experimental research involving human participants is sufficiently well designed to achieve the goal of generating clinically meaningful evidence. DOI: 10.1001/jamainternmed.2020.2904

Industry Updates

Researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) and The Ohio State University Wexner Medical Center are conducting a new clinical trial to determine if an oral cancer drug called ibrutinib can also help patients with cancer or other immunocompromised conditions recover from COVID-19. Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor. These drugs work by blocking specific chemical reactions in the body involved in cellular processes. For this phase II clinical trial, physicians at the OSUCCC - James will enroll up to 78 patients with cancer or a precancerous condition who have been hospitalized as a result of a COVID-19 infection. Patients will be randomized to receive either 14 days of standard treatment plus the study drug ibrutinib, or standard treatment alone. Press release.

Science 37 has announced a series of global investments, including an expanded European, Latin American and Asian nurse and investigator network, staffing in key European countries, and an operational center of excellence in Slovakia. The company hopes that by strengthening its global presence, it will enable sponsors to execute more decentralized clinical research without limitations. In addition to expanding global capacity, Science 37 continues to enhance its best-in-class technology platform that is now available in more than 40 languages—ensuring a seamless user experience for a myriad of international stakeholders. Press release.

A team of University of Pittsburgh, Michigan Medicine, Medical University of South Carolina and Stanford Medicine researchers recently were awarded funds from the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services (HHS), totaling more than $7 million to collaboratively study the role of convalescent plasma in mitigating symptoms of COVID-19 in patients with mild illness and preventing the progression of the disease from mild to severe. Conducted as part of the NHLBI Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) initiative, the Clinical Trial of COVID-19 Convalescent Plasma of Outpatients (C3PO) aims to evaluate whether passive immunization can be a safe and efficacious therapy in preventing the progression from mild to severe or critical COVID-19 illness and to understand the immunologic impact of anti-SARS-CoV-2 antibodies on the disease after passive immunization. Press release.

Researchers at Boston Children's Hospital and Brigham and Women's Hospital have launched a randomized, placebo-controlled clinical trial of dornase alfa (Pulmozyme) in patients with severe COVID-19 pneumonia and respiratory failure requiring mechanical ventilation. The study aims to enroll 60 adults and children (over age 3) admitted to intensive care units. Dornase alfa, also called DNase 1, is FDA-approved for patients with cystic fibrosis, to break up thick mucus secretions and prevent lung infections. The trial is supported by the Massachusetts Consortium on Pathogen Readiness, and the drug is being provided by Genentech, a member of the Roche Group, which is also providing supplementary financial support. Press release.

Yale School of Medicine and the biopharmaceutical firm AI Therapeutics—founded by Jonathan Rothberg—have launched a multi-institutional clinical trial of a drug for treating COVID-19. Known as LAM-002A (apilimod), the drug has a proven safety record. Preliminary research has shown it can block cellular entry and trafficking of the SARS-CoV-2 virus, the cause of COVID-19. The Yale Center for Clinical Investigation is now enrolling patients in a Phase II trial for the drug's use as a COVID-19 treatment. The study is expected to enroll 142 newly diagnosed patients to test the safety and efficacy of the drug in reducing virus levels in infected individuals. As the clinical trial is progressing, AI Therapeutics is preparing to make the LAM-002 accessible it has 70,000 doses ready to go, 70,000 on the way, and the compound in preparation for nearly 5 million more doses. Press release.

Moderna has announced the launch of Phase 3 of its mRNA vaccine candidate (mRNA-1273) against COVID-19 at nearly 100 clinical sites. Moderna is working closely with BARDA and the NIH, including NIAID’s COVID-19 Prevention Network (CoVPN), to conduct the Phase 3 COVE study under the auspices of Operation Warp Speed, and is collaborating with long-standing partner PPD. PPD supported the Phase 2 study for Moderna’s COVID-19 vaccine program, which completed the enrollment of 600 subjects at eight research sites within a month. PPD has contributed an array of clinical development and laboratory services, including strategic expertise to the study design, patient-enrollment epidemiology modeling and biostatistics. Press release.

The National Institute of Allergy and Infectious Diseases (NIAID) recently established the COVID-19 Prevention Network (CoVPN). Its goal is to register millions of volunteers for large-scale clinical testing of vaccines and monoclonal antibodies intended to protect people from COVID-19. As part of this initiative, Oracle developed a Cloud System called the CoVPN Volunteer Screening Registry to identify and screen volunteers who want to participate in COVID-19 clinical trials. More than 100,000 people have already registered. This program is expected to support hundreds of clinical trial sites across the United States and internationally by the end of the year. Press release.