With the pandemic of Covid-19 affecting the way of life across the globe, companies continue to accelerate the clinical development of a vaccine or a therapeutic. The number of Covid-19 clinical trials has been steadily growing since January 2020 because of the increase in the incidence rate and mortality. A first-in-human vaccine trial was initiated in early March by the National Institute of Allergy and Infectious Diseases (NIAID) with an mRNA candidate, mRNA-1273 by Moderna.
This trial is testing mRNA-1273 in 45 healthy male and non-pregnant female subjects ages 18–55 years, with an estimated end date in June 2021. However, a few trials investigating therapeutics for Covid-19 have been completed and disclosed the results of the investigations. Of the nine completed Covid-19 clinical trials, outlined in Table 1 below, all but one of these trials was sponsored by Chinese hospitals, the other being from a Chinese health clinical centre, signalling significant investments from the government and private sectors (institutions) within China. All trials were conducted in China, which is expected because this is where the virus was first reported and subject availability was plentiful. The majority (67%) of these trials were conducted in the Wuhan province, where the Covid-19 outbreak originated. All the primary interventions that were administered in these completed trials are therapeutics, not vaccines. In ongoing and planned trials, 4.7% of clinical trials are for a vaccine. More companies are expected to join the research.
Johnson &Johnson announced on 30 March that a vaccine candidate was selected and, in partnership with The Biomedical Advanced Research and Development Authority (BARDA), expects to initiate human clinical studies by September 2020, with the first batches of a Covid-19 vaccine possibly available for emergency use authorization in early 2021. In the trials that have been completed thus far, most of the drugs being used as a primary intervention are off-label and have been approved for the treatment of a different infectious disease, except for the trial investigating anti-2019-nCoV inactivated plasma. For example, danoprevir has been approved for the treatment of hepatitis C, while hydroxychloroquine was first approved for the treatment of malaria.
Despite the interim results showing reduction of Covid-19 virus load from an ongoing trial of hydroxychloroquine with azithromycin conducted in France’s Aix Marseille University, one of the completed clinical trials investigating hydroxychloroquine in combinations of antivirals did not achieve primary endpoints. The other trial investigating hydroxychloroquine alone did not disclose results. Over 65% of the completed clinical trials are either early stage (Phase 0, microdosing in human subjects) or late-stage (Phase IV). Majority of the primary interventions used in the nine completed trials were small molecules.
While all the trials were looking for efficacy and safety endpoints, only five trials successfully achieved the endpoint. First, favipiravir, originally marketed for the treatment of influenza, showed promising results from the two trials where it was used as the primary intervention. One of the trials with favipiravir showed effectiveness against Covid-19 with low adverse events and better treatment effects compared with the secondary intervention, lopinavir/ritonavir. Lopinavir/ritonavir, originally approved for the treatment of HIV/AIDS, was also tested in two clinical trials as the primary intervention but did not achieve the primary endpoint in one trial while the other was inconclusive. It did not significantly accelerate clinical improvement, reduce mortality, or diminish throat viral RNA levels in subjects with Covid-19.
Thus the results reported so far, even though some trials are encouraging, do not reveal any outstanding possible drug candidates. These are only a handful of single-country trials, with a limited number of subjects ranging from 10 to 240, and the results are rather mixed. Trials with danoprevir, meplazumab, favipiravir, and a Covid-19 to gain more insight from 29 ongoing clinical trials for Covid-19 with estimated end dates in April and more to follow that.