The Montreal Heart Institute recently announced that the independent data monitoring committee (DMC) of a clinical trial, after completing a futility analysis, recommended it continue to recruit non-hospitalized adult patients with COVID-19. A multinational, multisite, contact-free, at-home, double-blind, placebo-controlled clinical trial conducted in several Canadian regions, the United States, Europe, South America, and Africa. The Canadian sponsor and investigators seek to investigate if short-term treatment with colchicine reduces the rate of death and lung complications related to SARS-CoV-2, the virus behind the pandemic. The study team also investigates the safety and treatment with colchicine in this patient population. Interestingly, the drug used to treat gout attacks (and a few other ailments), has been in use since Greek antiquities. After one of the FDA’s “Unapproved Drug Initiatives,” a license was granted and the price shot up 2000% for colchicine, purportedly an “unintended” consequence. Can this gout treatment help treat COVID-19 patients?
Study Drug: Colchicine
Used to treat gout and Behcet’s disease and at times prevention of pericarditis and familial Mediterranean fever, the drug has a number of potential side effects, including low blood cells and rhabdomyolysis. Excessive doses can lead to death. The drug reduces inflammation via multiple mechanisms. In the form of autumn crocus, the drug has been around for thousands of years to treat joint swelling.
Based on a plant called the autumn crocus (Colchicum autumnale), the substance was used back in the Egyptian times circa 1500 BC. Fast forward to 2006 and an unintended consequence of the U.S. Food and Drug Administration (FDA) safety program known as the Unapproved Drugs Initiative, through which the agency sought out more rigorous testing of efficacy and safety of colchicine and other unapproved drugs. Post the review, the FDA granted a license and the price of the drug shot up 2000% for a gout remedy from ancient Greek times. That is because under the Unapproved Drugs Initiative, small ventures such as URL Pharma, a Philadelphia, PA drug producer, were rewarded with licenses for testing medicines such as colchicine. Takeda Pharmaceutical Co. acquired URL Pharma for $800 million, including the rights to colchicine (Colcrys), earning $1.2 billion in revenue by raising the price even more.
The Phase 3 clinical trial has been organized for its sponsor, the Montreal Heart Institute in collaboration with electronic data capture system Dacima Software, to investigate whether short-term treatment with colchicine in the patient population.
The study team seeks up to 6000 patients to receive either colchicine or placebo (1:1 allocation ration) for 30 days. Follow-up assessments are planned every 15 and 30 days following randomization for evaluation of the occurrence of any trial endpoints or other adverse events. Safety and efficacy is based on data from randomized patients.
An independent data and safety monitoring board (DSMB) periodically reviews study data results as well as the overall conduct of the study, and thereafter makes recommendations to the study Executive Steering Committee (ESC) to continue, stop or modify the study protocol.
In addition to sponsor Montreal Heart Institute other participating research centers include strategic collaborator NYU Grossman School of Medicine (Binita Shah, MD) as well as University of California, San Francisco (Priscilla Hsue, MD) and Hospital Universitario La Paz in Madrid, Spain (Jose Lopez-Sendon, MD), according to the study disclose on Clincialtrials.gov.
According to a recent Globe Newswire press release, the COLORONA study is coordinated by the Montreal Health Innovations Coordinating Center (MHICC) and funded by the Government of Quebec, the Bill & Melinda Gates Foundation, and the National Heart, Lung, and Blood institute (NHLBI) of the United States National Institutes of Health (NIH) and pharmascience. Note that Pharmascience is a generic drug maker and would potentially capitalize commercially if the study goes well.
Montreal Heart Institute
This organization, known as Montreal Heart Institute and founded in 1964, aims for the highest standards of excellence in the cardiovascular field through its leadership in clinical and basic research, ultra-specialized care, professional training, and prevention. It houses the largest research center in Canada, the largest cardiovascular prevention center in the country, and the largest cardiovascular genetics center in Canada. The institute is affiliated with the University of Montreal and has over 2,000 employees, including 254 doctors and over 85 researchers.
Dr. Jean-Claude Tardif is the Director of the Research Center at Montreal Heart Institute, Professor of Medicine at the University of Montreal, and Principle Investigator for COLCORONA study. Dr. Tardif reported recently, “We are pleased to have achieved this important milestone and now await the final results of COLCORONA, to determine the effect of colchicine in preventing complications in non-hospitalized patients with COVID.” The Montreal-based investigator continued “We are committed to including large number of patients worldwide in this robust study to determine the effect of colchicine on the serious inflammatory storm seen with COVID-19, potentially keeping patients out of the hospital and ultimately saving lives.”
Call to Action: TrialSite News will continue to monitor this trial and updates will be available—just sign up for the daily newsletter. Note, this article is included in PriceWatch as the drug, with roots in the antiquities, had its price increase by 2000% thanks to an FDA program. In this way, however cynical it may sound, the FDA ensures that an incredibly economic good becomes far less so via FDA regulation. Of course, the evaluation and license of the drug was ultimately to ensure the drug was safe but the consequence should be scrutinized further in any such case moving forward.