Clinical Trials of Therapeutics for COVID-19: Current Status

Clinical trials are vital for evaluating drugs and other therapeutics to assess their safety and efficacy in humans, so that they can eventually be used in clinical practice. These trials are all the more important under the current circumstances, when the COVID-19 pandemic is wreaking havoc across the globe. Targeted therapies against COVID-19 are urgently required as there is not a single specific treatment for this disease. The current pandemic is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19) SARS-CoV-2 is akin to SARS-CoV-1, which was discovered in 2003 in China, but the former is much deadlier than the latter. Another similar coronavirus is the Middle-East Respiratory Syndrome Coronavirus (MERS-CoV). It was discovered in Saudi Arabia in 2012. All these three viruses cause severe respiratory problems that can even lead to death.

Advertisement

Background of the Study

Currently, there is no effective treatment for COVID-19. As of April 2020, 1100 clinical trials have started for various treatments against COVID-19, of which 500 are randomized-controlled trials (RCT). These trials are registered in three major global clinical trial registries, namely, the National Institutes of Health’s ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform. Although these trials are much-needed, they also present challenges, including the potential for duplication of work and competition among researchers conducting the trials. Hence, the present study critically analyzed the data on currently ongoing clinical trials so that it could provide insightful guidance on how to overcome these challenges. The study was led by a team of scientists from the University of Melbourne, Australia.

Advertisement

Key Features of the Study

The study included only those clinical trials having potential to lead to actual treatments for clinical use

• 31 large-scale clinical trials were included in the study
• Each clinical trial included at least 1000 individuals
• Data was extracted primarily from the following three clinical trials registries:
• NIH’s ClinicalTrials.gov (www.clinicaltrials.gov)
• Australian New Zealand Clinical Trials Registry (www.anzctr.org.au)
• WHO International Clinical Trials Registry Platform (www.who.int/ictrp)
• The clinical trials were segregated into the following 4 categories:
• Drugs for prophylaxis (prevention) of COVID-19
• Treatments for outpatients with mild COVID-19
• Treatments for hospitalized patients with moderate COVID-19
• Treatments for critically ill patients with severe COVID-19
• Most of the drugs being tested in clinical trials have either of the following two properties:
• Exhibit in vitro antiviral effects against SARS-CoV-1, MERS-CoV or SARS-CoV-2
• Exhibit immunomodulatory effects that lessen the severity of uncontrolled lung inflammation in patients with late-stage COVID-19
• The top 3 drugs undergoing clinical trials include the following:
• Hydroxychloroquine – 24 trials
• Lopinavir / ritonavir – 7 trials
• Remdesevir – 5 trials

Advertisement

Key Findings of the Study

• Of the 31 large-scale clinical trials included in the study, almost all are scientist-driven and not conducted by pharmaceutical companies
• Most drug candidates of pharmaceutical companies haven’t reached a sufficiently advanced stage of development, making them unsuitable for undergoing clinical trials
• The majority of small-scale randomized clinical trials don’t proceed to large-scale trials due to lack of efficacy, safety issues, or commercial reasons
• However, these small-scale, early-phase clinical trials are crucial for replenishing the drug development pipeline, so that an effective drug against COVID-19 eventually emerges
• Majority of the clinical trials are evaluating chloroquine or hydroxychloroquine
• All of the antiviral drugs are being “repurposed” from existing licensed drugs used for treating other diseases
• Remdesevir – an antiviral against Ebola virus – is the only exception as it still remains unlicensed
• Some other large-scale clinical trials that are not yet registered, will evaluate the following:
• Convalescent plasma
• Angiotensin-2 receptor blockers (ARBs)
• Non-steroidal anti-inflammatory drugs (NSAIDs)

Key Challenges in Conducting Large-scale Clinical Trials

Large-scale clinical trials may pose many challenges, including the following:

• Competition between trials for study participants, funding sources and trial sites
• Duplication of work among various clinical trials, leading to wastage of valuable time, money and resources

Key Recommendations to Overcome the Challenges

Some of the ways to overcome the challenges include the following:

• Determining whether a clinical trial already exists that is similar to the trial being planned
• Co-ordination of clinical trials at the national and international levels to prevent duplication of trials
• Scientists conducting clinical trials should openly communicate among themselves with regard to:
• Trial protocols
• Data collection plans
• Source of the drug(s) being evaluated in the trial
• Scientists should regularly convey their study findings to the public through media briefings in order to maintain transparency

In conclusion, it may be said that clinical trials will be crucial and play a pivotal role in expediting the development of safe and effective therapeutics against COVID-19.

Well-designed, well-planned, and well-coordinated clinical trials that are executed in a timely manner, will ensure that an efficacious treatment for COVID-19 will become available within a matter of months, rather than the normal time-scale of decades!

Reference:

1. Clinical Trials for the Prevention and Treatment of Coronavirus Disease 2019 (COVID-19): The Current State of Play - (https://www.mja.com.au/journal/2020/clinical-trials-prevention-and-treatment-coronavirus-disease-2019-covid-19-current)

Source-Medindia