Safety and Immunogenicity Study of a SARS-CoV-2 (COVID-19) Variant Vaccine (mRNA-1273.351) in Naïve and Previously Vaccinated Adults
Condition: COVID-19; COVID-19 Immunisation
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase 1, open-label, randomized clinical trial in males and non-pregnant females,
      18 years of age and older, who are in good health, have no known history of COVID-19 or
      SARS-CoV-2 infection, and meet all other eligibility criteria. This clinical trial is
      designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273.351
      manufactured by ModernaTX, Inc, given in vaccination schedules alone, sequentially, or
      coadministered with mRNA-1273. mRNA-1273.351 is a novel lipid nanoparticle (LNP)-encapsulated
      mRNA-based vaccine that encodes for a full-length, prefusion stabilized S protein of the
      SARS-CoV-2 B.1.351 variant. Enrollment will occur at approximately five domestic clinical
      research sites.

      This study includes two cohorts. Cohort 1 will provide 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. Enrollment may close before the full 150 participants
      based on estimates on the timing of immunogenicity results and the need to inform public
      health decisions. 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 vaccination, as well
      as 3, 6 and 12 months post the last vaccination.

      The primary objective is to evaluate the safety and reactogenicity of mRNA-1273 and
      mRNA-1273.351 vaccines, in naïve and previously vaccinated individuals.
    

Detailed description: 
      This is a phase 1, open-label, randomized clinical trial in males and non-pregnant females,
      18 years of age and older, who are in good health, have no known history of COVID-19 or
      SARS-CoV-2 infection, and meet all other eligibility criteria. This clinical trial is
      designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273.351
      manufactured by ModernaTX, Inc, given in vaccination schedules alone, sequentially, or
      coadministered with mRNA-1273. mRNA-1273.351 is a novel lipid nanoparticle (LNP)-encapsulated
      mRNA-based vaccine that encodes for a full-length, prefusion stabilized S protein of the
      SARS-CoV-2 B.1.351 variant. Enrollment will occur at approximately five domestic clinical
      research sites.

      This study includes two cohorts. Cohort 1 will provide 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. Enrollment may close before the full 150 participants
      based on estimates on the timing of immunogenicity results and the need to inform public
      health decisions. 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 vaccination, as well
      as 3, 6 and 12 months post the last vaccination.

      The primary objective is to evaluate the safety and reactogenicity of mRNA-1273 and
      mRNA-1273.351 vaccines, in naïve and previously vaccinated individuals. The secondary
      objective is to assess humoral immunogenicity of mRNA-1273 and mRNA-1273.351 vaccines, in
      naïve and previously vaccinated individuals.
    

Intervention name(s): mRNA-1273; mRNA-1273.351
Intervention type(s): Biological; Biological
Intervention description(s): Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike protein of the Wuhan-Hu-1 strain of SARS-CoV-2. mRNA-1273 consists of an mRNA Drug Substance that is manufactured into LNPs composed of the proprietary ionizable lipid, SM-102, and 3 commercially available lipids, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and PEG2000 DMG.; Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike protein of the B.1.351 variant SARS-CoV-2 strain. mRNA-1273.351 consists of an mRNA Drug Substance that is manufactured into LNPs composed of the proprietary ionizable lipid, SM-102, and 3 commercially available lipids, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and PEG2000 DMG.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Coronavirus; COVID-19; Immunogenicity; mRNA-1273; mRNA-1273.351; SARS-CoV-2; SARS-CoV-2 B.1.351; vaccine