The world’s most significant coronavirus disease (COVID-19) vaccine study is underway in the United States, with a planned 30,000 volunteers. The phase 3 clinical trial aims to examine the efficacy and safety of the candidate vaccine developed by the National Institutes of Health and Moderna Inc.
The U.S. biotech firm Moderna announced that it had started the final stage of its human trials for its experimental COVID-19 vaccine in the U.S. The phase 3 human clinical trial comes after the company revealed promising results in its open-label phase 2 study, which showed that the vaccine, called mRNA-1273, induced an immune response against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.
A volunteer in Savannah, Georgia, received the first shot of the experimental vaccine in the phase 3 trial at 6:45 a.m. on July 27, Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said.
Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
The COVID-19 candidate vaccine, mRNA-1273, is an mRNA vaccine developed to protect against SARS-CoV-2. Moderna partnered with the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases of the NIH to develop the vaccine.
The team developed the vaccine based on the atomic-level structure assessment and study of betacoronavirus Spike proteins. These S-proteins guided the application of mutations to enhance their expression and immunogenicity.
The final phase trial
The phase 3 trial, called the Coronavirus Efficacy (COVE) study, will enroll 30,000 health people at about 89 sites around the country this summer. Half of the enrollees will receive two shots of the experimental vaccine, 28 days apart, and the other half will receive two shots of saltwater placebo. Neither the volunteers nor the medical staff administering the vaccines will know who will get the real vaccine. However, the researchers and those running the trial are the only ones who will receive the vaccine.
“We are pleased to have started the Phase 3 COVE study. We are grateful to the efforts of so many inside and outside the company to get us to this important milestone. We are indebted to the participants and investigators who now begin the work of the COVE study itself. We look forward to this trial demonstrating the potential of our vaccine to prevent COVID-19 so that we can defeat this pandemic,” Stephane Bancel, CEO at Moderna, said in a statement.
In the randomized, placebo-controlled trial, the participants will receive the 11 µg dose of the mRNA-1273. The primary endpoint will be the prevention of symptomatic development of COVID-19, and key secondary endpoints include the prevention of severe COVID-19, and prevention of infection by SARS-CoV-2, even without the symptoms.
Phase 3 trial participants will receive two intramuscular injections approximately 28 days apart. Participants will be randomly assigned 1:1 to receive either two 100 microgram (mcg) injections of mRNA-1273 or two shots of a saline placebo. The trial is blinded, so the investigators and the participants will not know who is assigned to which group.
Volunteers must provide informed consent to participate in the trial. They will be asked to provide a nasopharyngeal swab and a blood sample at an initial screening visit and additional blood samples at specified time points after each vaccination and over the two years following the second vaccination. Scientists will examine blood samples in the laboratory to detect and quantify immune responses to SARS-CoV-2.
Investigators will closely monitor participant safety. They will call participants after each vaccination to discuss any symptoms and will provide participants with a diary to record symptoms and a thermometer for temperature readings.
If a participant is suspected of having COVID-19, the participant will be asked to provide a nasal swab for testing within 72 hours. If the test is positive for SARS-CoV-2 infection, the participant will be followed closely and referred for medical care if symptoms worsen. Participants will be asked to provide a daily assessment of symptoms through resolution and have saliva sampled periodically so that investigators can test for SARS-CoV-2 infection.
Study investigators will regularly review trial safety data. An independent data and safety monitoring board (DSMB) will review blinded and unblinded data--including safety data and cases of COVID-19 in both groups--at scheduled data review meetings.
The phase 3 trial commenced after the results of its phase 1 trial, published in the New England Journal of Medicine, showed that the vaccine-induced immune responses in all of the volunteers and were deemed as generally safe to use. The vaccine only produced mild side effects, such as chills, fatigue, headache, muscle pain, and pain at the injection site.
In the phase 1 trial, only a small number of participants were given the vaccine so as to determine whether the vaccine triggered immune responses.
The phase 2 trial focused on expanding the number of participants, giving it to people who were at a higher risk of severe disease, such as those who are older and those with underlying health conditions. The last phase 3 stage is administered to thousands of people to test for effectiveness and safety.
Vaccine development and global toll
The Moderna trial is just one of the 25 clinical trials across the globe. Other candidate vaccines have also started their trials to determine their efficacy to prevent infection with the novel coronavirus.
The total number of infections around the world has already topped 16.48 million, with the death toll reaching more than 654,000. The United States remains as the nation with the highest infection toll, reaching more than 4.29 million individuals, while Brazil reports more than 2.44 million cases.
India, Russia, South Africa, and Mexico report high numbers of infections, with more than 1.48 million, 816,000, 452,000, and 395,000, respectively.