13 COVID-19 Vaccines Are in Human Clinical Trials – What Are They?
Industry Insight Jun 29, 2020 | By Molly Campbell, Science Writer, Technology Networks
The world is now several months into the COVID-19 global pandemic caused by the SARS-CoV-2 virus. As lockdown restrictions slowly begin to lift in certain regions, the pursuit for a safe and effective vaccine against the virus continues – and more research groups are joining the efforts.
"Over the course of 2020, the COVID-19 pandemic has caused an unprecedented global crisis, resulting in a devastating death toll and threatening our economic order and societal structures. So long as the virus is circulating somewhere, it remains a threat everywhere - no nation can end the pandemic by itself." – Dr Richard Hatchett, CEO of CEPI, in a press release.
The World Health Organization recognizes that, as of June 22, there are over 140 vaccines in various stages of development. Some are being fast-tracked by regulatory authorities, whilst others remain at the very early stages of pre-clinical testing.
Of those >140 vaccines, 13 are now in human clinical trials. If you're familiar with the drug development process, you'll know that this means they are enduring various phases of rigorous testing to explore their safety, efficacy and correct dosage in humans.
Only upon completion of such phases can a vaccine be considered as suitable for approval by authorities such as the Food and Drug Administration (FDA) or the Europeans Medicine Agency (EMA).
So, who are the 13, and where exactly are they in the testing process?
1. ChAdOx1 nCov-19
ChAdOx1 nCoV-19, a recombinant adenovirus vaccine developed by the University 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 candidate. The vaccine trial is steadily moving towards a Phase III trial, where a larger population is to be enrolled, consisting of 10,000 participants in the UK, and 30,000 participants enrolled in the United States 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.
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 and Phase II trials (NCT04283461 and NCT04405076). It was recently announced that the protocol for a Phase III study has been finalized which will enroll approximately 30,000 participants in the US and is expected to be conducted in collaboration with the National Institute of Allergy and Infectious Diseases.
“We look forward to beginning our Phase 3 study of mRNA-1273 with some 30,000 participants in July. Moderna is committed to advancing the clinical development of mRNA-1273 as safely and quickly as possible to demonstrate our vaccine’s ability to significantly reduce the risk of COVID-19 disease.” - Tal Zaks, M.D., Ph.D., Chief Medical Officer at Moderna, in a press release.
3. Adenovirus Type 5 Vector (Ad5-nCoV)
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 the Ebola virus in the past. Ad5-nCoV entered human clinical trials back in March based on positive preliminary safety data from animal models. It is currently in Phase I and Phase II studies (ChiCTR2000030906 and ChiCTR2000031781).
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 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.
NVX‑CoV2373 is a vaccine candidate that is engineered from the genetic sequence of SARS‑CoV‑2, developed by the late stage biotechnology company Novavax.
The vaccine has been created using Novavax's proprietary Matrix-MTM adjuvant, which was the subject of Technology Networks' recent interview with Dr Gregory Glenn about recently.
NVX-CoV2373 entered a Phase I/II trial in May (NCT04368988) and preliminary results are estimated to be released in July.
6. BNT162 vaccine program
In May, Pfizer and BioNTech announced that the first participants had been dosed in a clinical trial for the BTN162 vaccine program for COVID-19 (BNT162-01). The trial is exploring the safety and efficacy of four mRNA vaccine candidates. Each candidate represents a different combination of mRNA and a target antigen.
Together, Pfizer and BioNTech are preparing to scale up manufacturing of a vaccine should any of the candidates be successful, stating that their program should enable the production of millions of vaccine doses in 2020 and hundreds of millions in 2021.
“It is encouraging that we have been able to leverage more than a decade of experience in developing our mRNA platforms to initiate a global clinical trial in multiple regions for our vaccine program in such a short period. We are optimistic that advancing multiple vaccine candidates into human trials will allow us to identify the safest, most effective vaccination options against COVID-19,” BioNTech CEO and Co-founder, Ugur Sahin, in a press release.
INO-4800 is a DNA-based vaccine candidate developed by the biotech company Inovio Pharmaceuticals. The company state that a benefit of DNA medicines is the speed in which they can be created and manufactured, and the stability of the product with regards to freezing, storage and transport requirements. In early June, Inovio announced a partnership to start a Phase I/II clinical trial (NCT04336410) of the candidate in South Korea
Imperial College London scientists embarked on a Phase I clinical trial of the self-amplifying RNA vaccine LNP-nCoVsaRNA on June 23. When injected into the muscle, the vaccine causes the body's own cells to manufacture copies of the SARS-CoV-2 S protein, and these trigger the body to produce antibodies.
In the first stages of the trial, 15 healthy volunteers will receive the candidate, starting at a low dose and escalating to higher doses for subsequent volunteers to test the safety and deduce the optimal dosage. 300 healthy participants are anticipated to be enrolled in the trial and receive two doses of the vaccine, with larger clinical trials planned for later in the year should the data warrant them.
9. Gam-COVID-Vac Lyo
The Gameleya Research Institute, Health Ministry of the Russian Federation, is working on a Phase I clinical trial of the candidate Gam-COVID-Vac Lyo (NCT04437875). The vaccine combines Ad5 and Ad26, two adenoviruses that are both engineered with a coronavirus gene. The open two stage non-randomized Phase I study is recruiting healthy volunteers to test the safety, tolerability and immunogenicity of the candidate for the preparation of a solution for intramuscular administration.
10. CureVac's mRNA platform
CureVac announced that its mRNA vaccine candidate entered a Phase I clinical trial earlier in June. The aim of the trial is to determine optimal dosage as well as evaluating the safety and immune response to the vaccine in humans, recruiting 168 healthy participants. The mRNA vaccine candidate encodes the full-length S protein of SARS-CoV-2, and is formulated with lipid nanoparticles.
"During the last few months our team has put a lot of efforts into the preclinical validation of several vaccine candidates to select an optimal construct. We are confident that our early optimization work will provide a safe and effective low dose vaccine. In parallel, we are already producing large quantities of this trial medication under GMP conditions.” – Dr Franz-Werner Haas, acting CEO of CureVac, in a press release.
11. Inactivated SARS-CoV-2 Vaccine
Scientists at the Institute of Medical Biology at the Chinese Academy of Medical Sciences have started a Phase II trial of an inactivated SARS-CoV-2 vaccine (NCT04412538). The trial will evaluate safety and efficacy, adopting a randomized, double-blind and placebo-controlled approach in 942 healthy participants.
12 & 13. Inactivated Novel Coronavirus Pneumonia vaccine
China National Biotech Group Co Ltd (CNGB), Sinopharm's vaccine and bioscience unit, recently announced that it will conduct its Phase III trial of an inactivated novel coronavirus pneumonia vaccine candidate in the United Arab Emirates. This follows the report of positive data from Phase I/II trials that recruited 1,120 volunteers (ChiCTR2000031809).
The CNGB group are also working on a second inactivated vaccine candidate that has been co-developed by the Beijing Institute of Biological Products Co Ltd., and the Chinese Center for Disease Control and Prevention, which is in a Phase I/II trial (ChiCTR2000032459).
You can find an exhaustive list of the current vaccine candidates in development against COVID-19 here.