Cincinnati Children’s Hospital Starts Phase 1 Clinical Trial Targeting Modified mRNA-Vaccine for South African Variant

Cincinnati Children’s Hospital Starts Phase 1 Clinical Trial Targeting Modified mRNA-Vaccine for South African Variant

Cincinnati Children’s Hospital launched a new clinical trial involving what is a modified version of the Moderna COVID-19 (mRNA-1273) specifically targeting the South African variant. Led by Dr. Paul Spearman, the study investigates one of the more potent variants: can the modified Moderna version be more effective than the original product now under the U.S. Food and Drug Administration (FDA) emergency use authorization. One of four sites across the nation, Cincinnati Children’s Hospital seeks 30 participants for the study. Participants cannot have been subjected to the SARS-CoV-2 infection and have not yet been vaccinated. The study runs for 14 months and participants receive $1,000.

The Investigational Vaccine

This study involves a “tweaked” version of the Moderna vaccine known as mRNA-1273—the version targeting the South African variant is known as mRNA-1273.351. Principal investigator for Cincinnati Children’s Hospital, Dr. Paul Spearman, reports, “This one is formally known as b.1.351 or we just call it 351. The reason people are concerned about that is it looks like some of the vaccines that were being evaluated in South Africa at the time this virus was spreading, they were less effective in that population.”

But the mRNA-based vaccine purportedly has benefits. For example, Dr. Spearman suggests, “One of the advantages of the mRNA vaccines is that they can be modified relatively quickly. That’s why this trial is being offered so quickly after this vaccine was authorized.”

The Study

This Phase 1 open-label, randomized clinical trial (NCT04785144) in males and non-pregnant females includes participant aged 18 and up who are in good health and have no reported history of COVID-19 or SARS-CoV-2 infection, and meet all other eligibility criteria.

Sponsored by the National Institute of Allergy and Infectious Diseases(NIAID) in partnership with Moderna, this study’s set up to investigate the safety, reactogenicity and immunogenicity of the mRNA-1273.351 investigational vaccine developed by Moderna. This novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine encodes for a full-length, prefusion stabilized S protein of the SARS-CoV-2 B.1.351 variant. Enrollment occurs at up to five domestic clinical trial sites including Cincinnati Children’s Hospital, Vanderbilt University, Emory University and Kaiser Permanente Washington Health Research Institute—Vaccines and Infectious Diseases.

This study involves two (2) cohorts including 1) that provides rapid information about the immunogenicity of mRNA-1273.351 in a previously vaccinated group. This cohort can inform near term public health decisions if the variant virus becomes more widespread. Cohort 2 will evaluate different strategies for generation of cross protective immune responses in a naïve population. This cohort will take longer to provide information on the immunogenicity of mRNA-1273.351, but is important to inform future public health strategies. Cohort 1 will include approximately 60 subjects 18 years of age and older who received two vaccinations of mRNA-1273 at dosages of 50 mcg, 100 mcg, or 250 mcg in the Phase 1 clinical trial (DMID 20-0003).

Subjects in Cohort 1 will receive a single intramuscular (IM) injection of the designated vaccine and will be followed through 12 months after vaccination. Follow-up visits will occur on Days 8, 15, and 29, as well as 3, 6, and 12 months after the vaccination.

Cohort 2 will include approximately 150 participants 18 through 55 years of age who have not received a COVID-19 vaccine, have no known history of COVID-19 or SARS-CoV-2 infection, and do not have underlying conditions that are associated with an increased risk of severe illness from SARS-CoV-2 infection. They will be randomly assigned to one of 8 treatment arms and will receive 2 or 3 IM injections of the vaccine and followed through 12 months after the last vaccination. Follow-up visits will occur 7, 14, and 28 days after each through 12 months post the last vaccination. This cohort involves follow up visits occurring 7,14 and 28 days after each vaccination, as well as 3,6 and 12 months post the last vaccination. The goal here is to probe the safety and reactogenicity of mRNA-1273 and mRNA-1273.351 vaccines in naive and previously vaccinated individuals.

Investigator Point of View

Dr. Paul Spearman recently went on the record for NBC WLWT 5 that “There are a lot of variants out there. One of the ones people are most concerned about is the South African variant.” The principal investigator continued, “It’s harder to neutralize. It can still be neutralized, but it’s a concern for the future if it continues to spread.”

Lead Research/Investigator

Dr. Paul Spearman, MD

Call to Action: Interested in participating? Follow the link