Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis of SARS-CoV-2 Infection (COVID-19)
Condition: COVID-19; COVID-19 Immunisation
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I, open-label, dose-ranging clinical trial in males and non-pregnant females,
      starting at 18 years of age, inclusive, who are in good health and meet all eligibility
      criteria. This clinical trial is designed to assess the safety, reactogenicity and
      immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid
      nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion
      stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at up to 3 domestic
      clinical research sites. Up to one hundred and fifty-five subjects will be enrolled into one
      of thirteen cohorts (10 micrograms [mcg], 25 mcg, 50 mcg, 100 mcg, and 250 mcg). Subjects
      will receive an intramuscular (IM) injection (0.5 milliliters [mL]) of mRNA-1273 on Days 1
      and 29 in the deltoid muscle and will be followed through 12 months post second vaccination
      (Day 394). Follow-up visits will occur 1, 2, and 4 weeks post each vaccination (Days 8, 15,
      29, 36, 43, and 57), as well as 3, 6, and 12 months post second vaccination (Days 119, 209,
      and 394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose
      vaccination schedule of mRNA-1273, given 28 days apart, across 5 dosages in healthy adults.

      Optional Substudy:

      This is an optional third mRNA-1273 vaccination substudy, in subjects 18 years of age and
      older, who received both the first and second mRNA-1273 vaccinations in the main study and
      meet all other substudy eligibility criteria. This optional third mRNA-1273 vaccination
      substudy is designed to assess safety, reactogenicity, and immunogenicity through 12 months
      post third vaccination (Day 731). Subjects who receive the third mRNA-1273 vaccination will
      exit the Schedule of Activities for the main study and will enter the Schedule of Activities
      for the optional substudy. Up to one hundred and twenty subject will be enrolled into two
      cohorts (consisting of participating subjects who received 2 doses of 25 or 50 mcg and
      participating subjects who received 2 doses of 100 and 250 mcg). Subjects will receive an IM
      injection (0.5 mL) at a dosage of 100 mcg/0.5 mL. The primary objective is to evaluate the
      safety and reactogenicity of a third mRNA-1273 vaccination, at a dosage of 100 mcg.
    

Detailed description: 
      This is a phase I, open-label, dose-ranging clinical trial in males and non-pregnant females,
      starting at 18 years of age, inclusive, who are in good health and meet all eligibility
      criteria. This clinical trial is designed to assess the safety, reactogenicity and
      immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid
      nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion
      stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at up to 3 domestic
      clinical research sites. Up to one hundred and fifty-five subjects will be enrolled into one
      of thirteen cohorts (10 micrograms [mcg], 25 mcg, 50 mcg, 100 mcg, or 250 mcg). Subjects will
      receive an intramuscular (IM) injection (0.5 milliliters [mL]) of mRNA-1273 on Days 1 and 29
      in the deltoid muscle and will be followed through 12 months post second vaccination (Day
      394). Follow-up visits will occur 1, 2, and 4 weeks post each vaccination (Days 8, 15, 29,
      36, 43, and 57), as well as 3, 6, and 12 months post second vaccination (Days 119, 209, and
      394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose
      vaccination schedule of mRNA-1273, given 28 days apart, across 5 dosages in healthy adults.
      The secondary objective is to evaluate the immunogenicity as measured by Immunoglobulin G
      (IgG) enzyme-linked immunosorbent assay (ELISA) to the SARS-CoV-2 S (spike) protein following
      a 2-dose vaccination schedule of mRNA-1273 at Day 57.

      Optional Substudy:

      This is an optional third mRNA-1273 vaccination substudy, in subjects 18 years of age and
      older, who received both the first and second mRNA-1273 vaccinations in the main study and
      meet all other substudy eligibility criteria. This optional third mRNA-1273 vaccination
      substudy is designed to assess safety, reactogenicity, and immunogenicity through 12 months
      post third vaccination (Day 731). Subjects who receive the third mRNA-1273 vaccination will
      exit the Schedule of Activities for the main study and will enter the Schedule of Activities
      for the optional substudy. Up to one hundred and twenty subject will be enrolled into two
      cohorts (consisting of participating subjects who received 2 doses of 25 or 50 mcg and
      participating subjects who received 2 doses of 100 and 250 mcg). Subjects will receive an IM
      injection (0.5 mL) at a dosage of 100 mcg/0.5 mL. The primary objective is to evaluate the
      safety and reactogenicity of a third mRNA-1273 vaccination, at a dosage of 100 mcg. The
      secondary objective is to evaluate the immunogenicity as measured by IgG ELISA to the
      SARS-CoV-2 S protein following a third mRNA-1273 vaccination, at a dosage of 100 mcg, at all
      timepoints after the third mRNA-1273 vaccination.
    

Intervention name(s): mRNA-1273
Intervention type(s): Biological
Intervention description(s): Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike protein 2019-nCoV. 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, DSPC, and PEG2000 DMG.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: 2019-nCoV (mRNA-1273); COVID-19; Dose-escalation; Immunogenicity; novel coronavirus; Safety; SARS-CoV-2; vaccine