Which COVID-19 Vaccines Are in Human Clinical Trials?
Industry Insight Sep 03, 2020 | By Molly Campbell, Science Writer, Technology Networks
In ordinary times, vaccine development, testing and manufacturing is a process that can take several years to complete. In the context of the COVID-19 global pandemic, we are in far from ordinary times. Extreme efforts are underway across the world to create, test and distribute a safe and effective vaccine.
Over 140 vaccines for SARS-CoV-2 are under investigation according to the World Health Organization. As of September 3, there are 34 vaccine candidates in human clinical trials.
What are the 34, and where exactly are they in the testing process? This hub page is kept up-to-date with information on the latest vaccines entering human clinical trials, and their progress in testing.
Understanding the phases of vaccine clinical trials
A vaccine is given to a small number of people, typically between 20-100 individuals, to determine the safety and dosage in addition to assessing that an immune response occurs after vaccine administration.
A vaccine is given to a larger cohort of individuals – typically several hundred – that are separated into different groups, such as different age ranges, to determine whether the vaccine elicits a different response in different populations. Phase II trials also act as further validation of the safety of the vaccine and its ability to stimulate an immune response.
An even larger number of people are recruited to the trial – often a figure in the thousands – and the sample is randomized into individuals that will receive the vaccine and individuals that will receive a placebo. The outcomes are compared to determine which group has a better response, in this context, to the SARS-CoV-2 virus. A Phase III clinical trial is required before the FDA will approve a vaccine for use by the public.
You can explore the drug development process further here.
ChAdOx1 nCoV-19, a recombinant adenovirus vaccine developed by theUniversity of Oxford, entered human clinical trials back in April in the UK. The Phase I/II trial enrolled > 1000 healthy volunteers and aimed to test the safety and immune response triggered by the vaccine.
On July 20, the results of the Phase I/II trial were published in The Lancet. They demonstrate that the candidate vaccine was able to provoke a T cell response within 14 days of vaccination, in addition to an antibody response within 28 days.
The candidate vaccine recently entered a Phase III trial, where a larger population is to be enrolled, consisting of 10,000 healthy participants in the UK, and 30,000 participants in the US thanks to a collaboration with the pharma company AstraZeneca.
In early June, the Brazilian Health Regulatory Agency approved the inclusion of Brazil in the clinical trials of ChAdOx1 nCov-19, and it is estimated that 2,000 volunteers will be enrolled in the country.
"These encouraging results support further evaluation of this candidate vaccine in our ongoing large scale Phase III programme, that is still needed to assess the ability of the vaccine to protect people from COVID-19." – Professor Sarah Gilbert, professor of vaccinology at the University of Oxford Jenner Institute.
Adenovirus Type 5 Vector (Ad5-nCoV)
Phase I,II, III
Ad5-nCoV, developed by CanSino Biologics Inc. and the Beijing Institute of Biotechnology, is built upon CanSino's adenovirus-based viral vaccine technology platform, which has been utilized for infectious diseases such as Ebola in the past.
Ad5-nCoV entered human clinical trials in March based on positive preliminary safety data from animal models.
Results from the Phase II trial were published in The Lancet on July 20, and demonstrated that two different doses of the administered vaccine produced significant neutralizing antibody responses against SARS-CoV-2, with no serious adverse reactions documented.
The Chinese research team concluded that the results support testing of the vaccine in a Phase III effectiveness trial in healthy adults.
Phase I, III
The vaccine "Gam-COVID-Vac", developed by Moscow's Gamaleya Institute is an adenovirus-based vaccine – as is the ChAdOx1 vaccine being tested by the University of Oxford. It entered a Phase I clinical trial back in June which recruited 38 healthy participants to evaluate its safety, tolerability and immunogenicity. According to the National Institutes of Health clinical trials study record, this trial is still ongoing.
However, the Russian media reported that Russian Health Minister Mikhail Murashko had declared on August 1 that "clinical trials of a coronavirus vaccine developed by the Gamaleya Center are over, paperwork is underway for the vaccine’s registration." To date, Russia has not published any scientific data regarding Gam-COVID-Vac.
Phase I, II, III
mRNA-1273 is an mRNA vaccine developed against SARS-CoV-2 that encodes for a stabilized form of the virus' spike (S) protein. Developed by Moderna Inc., the vaccine candidate is currently in Phase I, II and III trials (NCT04283461, NCT04405076, NCT04470427).
Recently, Moderna announced that the company is in discussion with the Ministry of Health, Lavour and Welfare of Japan surrounding the potential purchase of 40 million + doses of mRNA-1273 to support the country's strategy to vaccinate the public as soon as possible.
"These positive Phase I data are encouraging and represent an important step forward in the clinical development of mRNA-1273, our vaccine candidate against COVID-19, and we thank the NIH for their ongoing collaboration. The Moderna team continues to focus on starting our Phase III study this month and, if successful, filing a BLA." - Stéphane Bancel, Chief Executive Officer of Moderna in a press release.
Phase I/II, II, III
The inactivated SARS-CoV-2 vaccine, CoronaVac, developed by the Chinese company Sinovac Biotech, is heading towards Phase III clinical trials in China and Brazil, the company recently announced.
This is due to positive preliminary results from a Phase I/II trial involving 743 participants, where no severe adverse effects were observed and immune responses were produced (NCT04383574).
“Our phase I/II study shows CoronaVac is safe and can induce an immune response. Concluding our phase I/II clinical studies with these encouraging results is another significant milestone we have achieved in the fight against COVID-19.” - Mr. Weidong Yin, Chairman, President and CEO of Sinovac, in a press release.
BTN162 vaccine program
Phase I/II, III
Pfizer is working in collaboration with the German company BioNTech on a COVID-19 vaccine program known as BTN162 which will test several mRNA-based vaccine candidates. In a recent press release, BioNTech shared positive early data on their lead candidate NT162b2.
BTN162b2 is still under clinical study, but assuming that testing is successful, Pfizer and BioNTech are keen to seek regulatory approval as early as October 2020 according to a press release. Current plans are to supply up to 100 million doses across the glove by the end of 2020, and approximately 1.3 million doses by the end of the following year.
“We are especially pleased to offer these early data showing our vaccine candidate’s promising safety and immunogenicity profile from the U.S. trial and we look forward to sharing T cell immune response data from the German trial in the near future.”- Kathrin U. Jansen, Senior Vice President and Head of Vaccine Research & Development, Pfizer, in a press release.
|NVX CoV2373||Novavax ||I/II, II|
|GRAd-COV2 ||ReiThera, LEUKOCARE and Univercells||I|
|INO-4800||Inovio Pharmaceuticals and the International Vaccine Institute||I/II|
|LNP-nCoVsaRNA||Imperial College London||I|
|Adjuvanted recombinant protein-based vaccine||Sanofi Pasteur and GSK||I/II|
|mRNA vaccine candidate||CureVac||I, II|
|Inactivated novel coronavirus pneumonia vaccine||Wuhan Institute of Biological Products and Sinopharm||I/II, III|
|Inactivated novel coronavirus pneumonia vaccine||Beijing Institute of of Biological Products and Sinopharm||I/II, III|
|Inactivated SARS-CoV-2 vaccine||Chinese Academy of Medical Sciences||I, II|
|Adjuvanted recombinant protein (RBD-Dimer)||Anhui Zhifei Longcom Biopharmaceutical, Institute of Microbiology and the Chinese Academy of Sciences||I, II|
|DNA plasmid vaccine||Osaka University, AnGes and Takara Bio||I/II|
|Receptor binding domain-based vaccine||Kentucky Bioprocessing||I/II|
|S-Trimer vaccine||Clover Biopharmaceuticals, GSK and Dynavax||I|
|Recombinant spike protein with Advax™ adjuvant||Vaxine Pty and Medytox||I|
|DNA vaccine (GX-19)||Genexine Consortium||I/II|
|Whole-virion inactivated vaccine||Bharat Biotech||I/II|
|DNA plasmid vaccine||Cadila Healthcare||I/II|
|Molecular clamp stabilized S protein with MF59 adjuvant||University of Queensland, CSL and Seqirus||I|
Plant-derived VLP adjuvanted with GSK or Dynavax adjs
|People's Liberation Army (PLA) Academy of Military Sciences and Walvax Biotech.|
|Ad26COVS1||Janssen Pharmaceutical Companies||I/II, III (not yet recruiting)|
|Replicating viral vector||Institute Pasteur, Themis, University of Pittsburg CVR and Merck Sharp & Dohme||I|
|RBD (baculovirus production expressed in Sf9 cells)||West China Hospital and Sichuan University||I|
|Peptide vaccine||FBRI SRC VB VECTOR, Rospotrebnadzor, Koltsovo||I|
|Protein subunit vaccine||Instituto Finlay de Vacunas, Cuba||I|
|Subunit vaccine candidate with Dynavax’s CpG 1018||Medigen Vaccine Biologics Corporation/NIAID/Dynavax||I|
|Inactivated vaccine||Research Institute for Biological Safety Problems, Rep of Kazakhstan||I/II|
You can find an exhaustive list of the current vaccines in development against COVID-19 here.
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