A Phase 1/2 Study to Assess the Safety and Immunogenicity of JCXH-221, an mRNA-based Broadly Protective COVID-19 Vaccine

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about, test, and compare JCXH-221 in healthy volunteers. The main aims to answer are: To assess the safety and tolerability of the JCXH-221 vaccine in healthy adult subjects To identify an optimal dose for the JCXH-221 vaccine in healthy adult subjects To assess the humoral immunogenicity of the JCXH-221 vaccine in healthy adult subjects To characterize the cellular immunogenicity of the JCXH-221 vaccine in healthy adult subjects Participants for Phase I will be randomized to either JCXH-221 or placebo. In Phase 2, participants will be randomized to either JCXH-221 or a FDA approved Active comparator.

Detailed Description
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This is a phase 1/2 study looking to enroll a total of 262 patients. For phase 1, two cohorts will be explored (18-64 age group and 65+ age group) for a total of 72 subjects. The subjects will be enrolled and randomized to either placebo or JCXH-221. A low dose of JCXH-221 will be explored vs placebo for each age group first. A high dose for those 2 cohorts will be explored once all safety data is reviewed. Once all of Phase 1 data has been reviewed, Phase 2 enrollment will open. In this portion of the trial, subjects will be enrolled and randomized to either JCXH-221 or a FDA approved Active comparator (Pfizer, Moderna, etc.). A total of 190 patients will be enrolled.

Official Title
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A PHASE 1/2 STUDY TO ASSESS THE SAFETY AND IMMUNOGENICITY OF A BROADLY PROTECTIVE mRNA VACCINE JCXH-221 AGAINST SARS-CoV-2 INFECTION AND DISEASES

Conditions
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COVID-19, Infectious Disease

Intervention / Treatment
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* Biological: JCXH-221
* Biological: Active Comparator
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria Sex: Male or female; female subjects may be of childbearing potential, of nonchildbearing potential, or postmenopausal. Age: 18 years of age or older, at screening. Status: Healthy subjects. Subjects must have completed the full doses for primary vaccination with an approved SARS-CoV-2 vaccine and may have received booster dose(s), with the last vaccination (can be 2nd dose of primary vaccination or booster dose) having occurred at least 4 months prior to enrollment. Main Exclusion Criteria Current or prior symptomatic or asymptomatic SARS-CoV-2 infection confirmed by an approved or authorized rapid antigen test on Day 1 or within 4 months prior to Day 1. Subjects with significant exposure (as defined by current CDC guidance) to someone with laboratory confirmed SARS-CoV-2 infection or COVID-19 with the past 14 days prior to the Screening visit. Subjects with fever or signs of acute infection at the time of enrollment and vaccination. Subjects who are taking medications that may prevent or treat COVID-19. Subjects who received convalescent serum or prior therapeutic antibodies against SARS-CoV-2 within 4 months before Day 1. Subjects with history of myocarditis or pericarditis, or with AEs after mRNA vaccination that are in nature and severity beyond the common AEs expected and necessitating medical intervention. Subjects with active or suspected immunosuppression, immunodeficiency, or autoimmune disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 age groups will be enrolled in parallel for Phase 1 (18-64 age group and 65+ age group). Phase 2 will be a single age group of 18+.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational product<br>Patients randomized to this arm will be given the investigational product (JCXH-221). | Biological: JCXH-221<br>* Participants will be randomized to either placebo or JCXH-221 for Phase 1. For Phase 2, participants will either be randomized to JCXH-221 or a FDA approved Active comparator.<br>|
| Placebo Comparator: Placebo<br>Patients randomized to this arm will be given a placebo vaccine. | Other: Placebo<br>* Participants will be randomized in Phase 1 to either JCXH-221 or placebo<br>|
| Active Comparator: Active Comparator<br>Patients randomized to this arm will be given an active FDA approved COVID-19 Vaccine (Pfizer, Moderna, etc.). | Biological: Active Comparator<br>* Participants will be randomized in Phase 2 to either JCXH-221 or a FDA approved Active Comparator,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAE frequency | Frequency of serious adverse events (SAEs) characterized by type, severity, duration, and drug relationship, from Day 1 (dosing day) until follow-up completion | Day 1- Day 365 (12 months) | 
| Injection site reaction | Solicited local reactions at the injection site characterized by frequency, severity, and duration, recorded up to 7 days after dosing (Day 8) | Day 1- Day 8 (7 days) | 
| Solicited systemic reaction frequency | Solicited systemic reactions characterized by frequency, severity, duration, and drug relationship, recorded up to 7 days after dosing (Day 8) | Day 1- Day 8 (7 days) | 
| AE frequency | Adverse events (AEs), including unsolicited AEs, characterized by frequency, severity, duration, and drug relationship, for up to 28 days after dosing (Day 29) | Day 1- Day 29 (28 days) | 
| Unsolicited treatment-emergent AE frequency | The proportion of subjects with at least 1 unsolicited treatment-emergent AE occurring up to 28 days after dosing (Day 29) | Day 1- Day 29 (28 days) | 
| Medical AE frequency | Medically attended AEs (MAAEs) characterized by frequency, severity, duration, and drug relationship, from Day 1 until follow-up completion | Day 1- Day 365 (12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 antibody levels | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific serum neutralizing antibody levels against ancestral and variant SARS-CoV-2 strains as compared to baseline (Day 1 predose) at 7, 14, and 28 days after dosing, and 2, 4, and 6 months after dosing: Geometric mean titers (GMTs) at each time point Geometric mean-fold rise (GMFR) from before vaccination to each subsequent time point after vaccination Seroresponse rate (SRR) defined as the proportion of subjects achieving ≥4-fold rise from before vaccination to each subsequent time point after vaccination | Day 1- Day 181 ( 6 months) | 
| SARS-CoV-2 anti-receptor antibody levels | SARS-CoV-2 anti-receptor binding domain (RBD) antibody levels as compared to baseline (Day 1 predose) at 7, 14, and 28 days after dosing, and 2, 4, and 6 months after dosing Geometric mean concentrations (GMCs) at each time point GMFR from before vaccination to each subsequent time point after vaccination SRR defined as the proportion of subjects achieving ≥4-fold rise from before vaccination to each subsequent time point after vaccination | Day 1- Day 181 ( 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA Vaccine, COVID vaccination, Healthy subjects