LEXINGTON, Ky. — Clinical leaders from the University of Kentucky’s Markey Cancer Center, College of Medicine and College of Pharmacy have launched a clinical trial for experimental therapies to treat patients infected with COVID-19.
The trial will investigate the effectiveness of azithromycin, ivermectin and camostat mesylate—drugs that could inhibit replication of SARS-CoV-2, the virus that causes the disease. The three will be tested either as stand-alone therapies or in combination with the antimalarial drug hydroxychloroquine.
The trial has a “pick-the-winner” design, which will allow UK researchers to rapidly understand what potential therapies appear to be effective, guiding patients to treatments that work and researchers to promising drugs that warrant further investigation.
“We are pleased to be able to offer this clinical trial to patients with COVID-19 in Kentucky. While there is no standard treatment for COVID-19, this trial gives us the ability to test multiple therapies rapidly in order to identify the most promising agents,” said Dr. Susanne Arnold, a medical oncologist and associate director of clinical translation at the UK Markey Cancer Center who is co-leading the trial. “This rapid assessment means that the trial can quickly include and test new therapies as it identifies ones that are not effective.”
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The team plans to scale up a larger, more traditional placebo-control clinical trial using the most promising therapies with the best patient outcomes.
This trial is reserved for patients who have tested positive for COVID-19, or who have COVID-19 symptoms but have not developed severe symptoms that would require progression to ICU care. Patients must also have at least one high-risk feature, including hypertension, diabetes, cancer, lung disease, have an underlying heart condition, or be over the age of 50. Patients are then enrolled through UK Healthcare’s Infectious Diseases (ID) division under the direction of Dr. Alice Thornton and treated by UK HealthCare ID staff. Researchers began consenting patients the first week of May and plan to enroll 240 patients over the course of the study.
“The goal is to prevent patients from getting severe cases of the disease that would require hospitalization or put them in the ICU or on a ventilator,” said Dr. Zachary Porterfield, an infectious disease expert, virologist and assistant professor of medicine at UK who is co-leading the study with Arnold. “No proven therapies have been demonstrated to prevent progression of COVID-19 to severe illness. This is a critical unmet need for high-risk individuals that would also reduce the strain on our health care system.”
Patients with cases of COVID-19 who choose to enroll in the trial will be randomly assigned to one of four treatment groups: one group will receive hydroxychloroquine alone; a second group will receive hydroxychloroquine and azithromycin; a third group will receive hydroxychloroquine and ivermectin; and a fourth group will receive camostat mesylate.
“The medications were selected by a multidisciplinary committee of medical experts from across the university. These were chosen as some of the most unique and promising initial trial study drugs that can be offered at the moment. Not only do they have some data to suggest they may work against COVID-19, these are all oral medications that are widely available and could have an effect worldwide,” said Porterfield.
Hydroxychloroquine and azithromycin are generic formulations long used to treat other conditions and their combined use has already shown promise in some early COVID-19 clinical trials. Hydroxychloroquine is used for the prevention and treatment of malaria as well as for autoimmune disorders including lupus and rheumatoid arthritis. In past research, it also showed some effectiveness against related coronaviral diseases MERS and SARS. Azithromycin is an antibiotic with an immunomodulatory effect that is used to treat many types of infections caused by bacteria, including respiratory, skin, ear and eye infections.
Ivermectin is an antiparasitic agent that also has activity in cellular models against a number of RNA viruses, including influenza, equine encephalitis and West Nile and appears to affect the entry of viral RNA into the cell nucleus.
Camostat mesylate is a serine inhibitor that has been used in Japan for 40 years to treat symptoms of chronic pancreatitis and postoperative esophageal reflux. Studies show that camostat mesylate can prevent cleavage of the spike protein in SARS-CoV-2, which is necessary for the virus to infect cells. The UK trial will be among the very first in the world to include this novel treatment.
UK’s COVID-19 related research is coordinated by the COVID-19 Unified Research Experts (CURE) Alliance team, which is uniting UK medical researchers across disciplines in the fight against the novel coronavirus. The Alliance was launched and is supported by UK College of Medicine Dean Robert DiPaola and Vice President for Research Lisa Cassis. The CURE team is led by Rebecca Dutch, a virologist and chair of the department of molecular & cellular biochemistry.
The design and implementation of this trial is a testament to the collaborative and interdisciplinary nature of the CURE Alliance. Key insights in the trial have been provided by experts from across the university including Dr. Elijah Kakani, a hospitalist physician who has been dedicated to developing the camostat mesylate arm of the trial, to Kip Guy, dean of the College of Pharmacy, who has led a team of individuals in the evaluation of novel drug targets to be included in the trial, to Ken Campbell who has created a centralized biobank for management of blood and other samples from participants to help support crucial COVID-19 research.
In addition to principal investigators Arnold and Porterfield, this study includes several co-investigators, including Jill Kolesar, Dr. Zin Myint, Heidi Weiss, Donglin Yan, Dr.Therese Bocklage from the Markey Cancer Center; Dr. Miguel Villalona Calero, Dr. Aaron Hesselson from the College of Medicine; Jared Hammill and Frank Romanelli from the College of Pharmacy; and Scott Berry from the College of Engineering. Additional collaborators and consultants include Dr. Phil Kern, DiPaola, and Vivek Rangnekar.
Organizers are still recruiting volunteers to enroll in this clinical trial. Patients must be over 18 years old, have at least one high-risk feature listed above and have tested positive for COVID-19 in the last seven days. They must also have the ability to return to UK HealthCare for repeated testing and observation.