NIH Clinical Trial Begins Evaluating Moderna COVID-19 Variant Vaccine

Press release

Wednesday March 31, 2021

Early trial to assess safety and immunogenicity.

An investigational vaccine designed to protect against the B.1.351 variant of SARS-CoV-2 was administered in a new phase 1 clinical trial evaluating the safety and immunogenicity of the vaccine candidate in adult volunteers. The vaccine, known as mRNA-1273.351, was developed by the biotechnology company ModernaTX, Inc., based in Cambridge, Massachusetts. The trial is led and funded by the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health. The trial will recruit approximately 210 healthy adult volunteers at four clinical research sites in the United States that are part of the NIAID-funded Infectious Diseases Clinical Research Consortium (IDRC).

“The B.1.351 variant of SARS-CoV-2, first identified in the Republic of South Africa, has been detected in at least nine states in the United States,” said Anthony S. Fauci, MD, director of NIAID. The COVID-19 vaccines currently available in the United States are expected to provide an adequate level of protection against the SARS-CoV-2 variants. However, out of caution, NIAID continued its partnership with Moderna to evaluate this variant of the vaccine candidate in the event of a need for an updated vaccine.

Researchers at NIAID and Moderna have co-developed the mRNA-1273 vaccine, which is currently cleared by the United States Food and Drug Administration for emergency use in the United States for the prevention of COVID-19 in adults aged 18 and over. The vaccine is given in two doses of 100 micrograms (mcg) 28 days apart. The vaccine uses lipid nanoparticles to deliver instructions to the body’s cells to make a stabilized version of the spike protein found on the surface of the SARS-CoV-2 virus. After vaccination, the immune system detects the stabilized spike protein and begins to build a response against the virus. The variant vaccine candidate developed by Moderna, mRNA-1273.351, differs from the currently licensed Moderna vaccine in that it provides instructions for making the SARS-CoV-2 peak that incorporates key mutations in the B.1.351 virus variant. . In addition to the Phase 1 clinical trial, researchers at NIAID’s Vaccine Research Center are collaborating with Moderna to evaluate mRNA-1273.351 in animal models.

The trial will recruit people aged 18 and older who have previously received the mRNA-1273 vaccine, as well as people aged 18 to 55 who have not received a COVID-19 vaccine. Approximately 60 volunteers who have already received mRNA-1273 as a participant in NIAID’s Phase 1 mRNA-1273 trial (which began in March 2020) will enroll in the new variant of the trial. phase 1. About a year ago, these volunteers received two mRNA-1273 vaccinations 28 days apart at varying doses: 50 mcg, 100 mcg or 250 mcg. As part of the variant vaccine trial, these volunteers will be randomized to receive either a single booster vaccination of 50 mcg mRNA-1273.351 (group 1A) or a single vaccination containing a 25 mcg dose of mRNA-1273 and a 25 mcg dose of mRNA-1273,351 (group 1B). The remaining participants in the March 2020 trial will be offered a booster injection of mRNA-1273 as part of a separate clinical trial protocol (for more information, see clincialtrials.gov: NCT04283461).

The phase 1 variant vaccine trial will also recruit approximately 150 volunteers aged 18 to 55 who have not received any COVID-19 vaccine, have no known history of infection with COVID-19 or SARS. -CoV-2 and do not have any health problems that are associated with an increased risk of serious illness due to infection with SARS-CoV-2, such as cancer, heart disease, type 2 diabetes mellitus, severe obesity or chronic renal failure. These volunteers will be randomly assigned to one of the eight cohorts:

• Group 2A (15 participants) will receive three vaccinations 28 days apart: 100 mcg mRNA-1273, followed by 100 mcg mRNA-1273, followed by 50 mcg mRNA-1273.351.
• Group 2B (15 participants) will receive three vaccinations 28 days apart: 50 mcg mRNA-1273, followed by 50 mcg mRNA-1273, followed by 50 mcg mRNA-1273.351.
• Group 2C (20 participants) will receive two vaccinations 28 days apart: 100 mcg mRNA-1273.351, followed by 100 mcg mRNA-1273.351.
• Group 2D (20 participants) will receive two vaccinations 28 days apart: 50 mcg mRNA-1273.351, followed by 50 mcg mRNA-1273.351.
• Group 2E (20 participants) will receive two vaccinations 28 days apart: 100 mcg mRNA-1273, followed by 100 mcg mRNA-1273.351.
• Group 2F (20 participants) will receive two vaccinations 28 days apart: 50 mcg mRNA-1273, followed by 50 mcg mRNA-1273.351.
• The 2G group (20 participants) will receive a single vaccination on their initial visit which combines 50 mcg of mRNA-1273 plus 50 mcg of mRNA-1273.351. Twenty-eight days later, they will receive another single vaccination of the same dose and the same combination.
• The 2H group (20 participants) will receive a single vaccination on their initial visit which combines 25 mcg of mRNA-1273 plus 25 mcg of mRNA-1273.351. Twenty-eight days later, they will receive another single vaccination of the same dose and the same combination.

The trial will assess the safety and reactogenicity of the vaccine candidate as well as its ability to induce an immune response. Reactogenicity may include injection site reactions such as redness and pain as well as systemic reactions such as fever, headache, fatigue, or muscle pain. Participants will be closely monitored for safety and will be asked to return to the study clinic for several follow-up visits between vaccinations and for additional visits during the year following their last vaccination. Participants will also be asked to provide blood samples at specific times throughout the trial. Scientists will use these samples to measure the immune response against circulating strains of SARS-CoV-2, including the B.1.351 variant.

An independent Safety Oversight Committee (SMC) will oversee the test by regularly reviewing safety reports. The MSC can make a recommendation to the sponsor (NIAID) whether the trial should be interrupted, modified or terminated at any time.

The Phase 1 clinical trial will recruit participants at the Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle, Emory University in Atlanta, Vanderbilt University Medical Center (VUMC) in Nashville, Tennessee, and Cincinnati Children’s Hospital Medical Center (CCHMC). The trial is being led by investigators Lisa A. Jackson, MD, MPH, principal investigator at KPWHRI; Evan Anderson, MD, professor of pediatrics and medicine at Emory; Nadine Rouphael, MD, professor of medicine at Emory; C. Buddy Creech, MD, MPH, director of the Vanderbilt Vaccine Research Program and Associate Professor of Pediatrics at Vanderbilt; and Paul Spearman, MD, director of the Division of Infectious Diseases at CCHMC. These clinical research sites are four of the ten Vaccine and Treatment Assessment Units (VTEUs) that make up IDRC. The IDRC steering group is also providing scientific oversight and operational support for this trial.

The researchers predict that the trial will be fully recruited by the end of April 2021. The results of this trial will inform further evaluation of vaccine variant strategies if an updated vaccine is needed. The FDA recently issued guidelines for vaccine developers seeking to modify an emergency use authorization to deal with new variants. For more information about the study, visit ClinicalTrials.gov and search for ID NCT04785144.

NIAID conducts and supports research – at the NIH, in the United States, and around the world – to study the causes of infectious and immune-mediated diseases and to develop better ways to prevent, diagnose, and treat these diseases. Press releases, fact sheets and other materials related to NIAID are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the country’s medical research agency, comprises 27 institutes and centers and is a component of the US Department of Health and Human Services. The NIH is the principal federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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