This will be a Phase 1/2, multicenter, dose-finding study in healthy subjects 18 years of age or older to assess the safety, tolerability, and immunogenicity of a single dose of JCXH-221, a lipid nanoparticle complexed messenger ribonucleic acid (mRNA)-based broadly protective vaccine in development for the prevention of SARS-CoV-2 infection and diseases.
Phase 1 will be a randomized, double-blinded, placebo-controlled, dose-escalation study and will assess the safety and immunogenicity of 2 different dose levels in 2 age groups: 18 to 64 and ≥65 years of age. The starting dose will be 20 µg, administered to Cohorts 1a and 2a, and the higher dose will be 50 µg, administered to Cohorts 1b and 2b. In this double-blinded study, the subjects and the Investigators/designees will be blinded to treatment assignment.
There will be 4 cohorts in Phase 1, based on age and dose level. For each cohort, eligible subjects will be randomized to receive either JCXH-221 or placebo (5:1). Enrollment for Cohorts 1a and 2a will start first and can happen concurrently. If safety is demonstrated, Cohorts 1b and 2b will be opened to enrollment, and subjects will receive the higher dose level or placebo.
Once all subjects in Phase 1 have completed 1 month of study participation, data from all 4 cohorts will be evaluated for safety and immunogenicity. If the safety is acceptable and the vaccine induces the expected serological response for the ancestral (Wuhan) and variant SARS-CoV-2 strains (Delta and Omicron), Phase 2 of the study may be initiated.
Phase 2 of the study will be a randomized, double-blinded, active-controlled study in approximately 190 subjects 18 years of age or older, to further characterize the safety and immunogenicity of JCXH-221. The study subjects and the Investigators/designees will be blinded.
Subjects will be randomized 1:1 to receive JCXH-221 or a currently approved or authorized SARS-CoV-2 bivalent mRNA vaccine booster on Day 1. Sentinel dosing is currently not planned for Phase 2.
If the safety and immunogenicity data from Phase 1 appear comparable between the 2 age groups, in Phase 2 of the study, the 2 age groups will be combined (≥ 18 years of age); otherwise, subjects in Phase 2 may also be grouped by age (i.e., 18-64 and ≥ 65 years of age).
Cohort 1a (18-64 years old) : A single intramuscular (IM) dose of 20 µg JCXH-221 (n=15) or placebo (n=3)
Cohort 1b (18-64 years old) : A single IM dose of 50 µg JCXH-221(n=15) or placebo (n=3)
Cohort 2a (≥65 years old) : A single IM dose of 20 µg JCXH-221 (n=15) or placebo (n=3)
Cohort 2b (≥65 years old) : A single IM dose of 50 µg JCXH-221 (n=15) or placebo (n=3)
All subjects* : A single IM RP2D of JCXH-221 (n=95) or active comparator (n=95)
*Note: Based on Phase 1 data review, subjects in Phase 2 may be divided into 2 groups by age; if an RP2D
cannot be determined based on Phase 1 data review, 2 dose levels may be tested.