A First-in-Human Study to Evaluate JCXH-105, an srRNA-based Herpes Zoster Vaccine

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess the safety and immunogenicity of a self-replicating (sr) RNA-based vaccine, JCXH-105, in the prevention of Shingles (Herpes Zoster) Participant will be randomized to receive either JCXH-105 or Shingrix.

Detailed Description
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This Phase 1 study plans to enroll a total of 75 participants. Three cohorts with 3 different dose levels of JCXH-105 will be explored and each cohort will enroll 25 participants (20 randomized to JCXH-105 and 5 randomized to Shingrix) for a total of 75 participants. The dose level of JCXH-105 will depend on the time the participant joins the study. Each participant will receive two single intramuscular (IM) injections of study treatment (JCXH-105 or Shingrix) on day 1 and day 61 (±2 days on day 61)

Official Title
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A Phase 1 Randomized, Double-Blinded, Active-Controlled, 2-Dose Study to Assess the Safety and Immunogenicity of a Herpes Zoster (HZ) Vaccine, JCXH-105, in Healthy Subjects 50 to 69 Years of Age.

Conditions
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Herpes Zoster (HZ), Shingles, Infectious Disease

Intervention / Treatment
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* Biological: JCXH-105
* Biological: Active Control (Shingrix)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sex: Male or female; female subjects may be of childbearing potential, of nonchildbearing potential, or postmenopausal. Age: 50 to 69 years of age, inclusive, at screening. Status: Healthy subjects. Note: Healthy status as defined by the absence of evidence of any clinically significant active or chronic disease, in the opinion of the Investigator, following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG) recording, hematology, blood chemistry, serology, and urinalysis. Healthy subjects may have stable pre-existing disease defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks prior to enrollment. Subjects must agree to not be vaccinated with any HZ vaccine while participating in this study. All values for hematology and clinical chemistry tests of blood and urine within the normal range OR showing no clinically relevant deviations based on medical history, considering stable pre-existing diseases (see Healthy Subjects above), as judged by the Investigator. Exclusion Criteria: Subjects with a history of HZ or current diagnosis of shingles. Previous vaccination against HZ. Subjects with any respiratory illness deemed clinically relevant by the Investigator within the past month OR hospitalization >24 hours for any reason within the past month prior to the first vaccine administration (JCXH-105 or Shingrix). Subjects with history of myocarditis or pericarditis, or with AEs after mRNA vaccination that are in nature and severity beyond the common expected AEs necessitating medical intervention. Subjects who have received an mRNA-based vaccine (e.g., Spikevax, Comirnaty, etc.) 30 days prior to Day 1. Subjects who received any non-live vaccine within 14 days prior to the first vaccine administration (JCXH-105 or Shingrix). Subjects who received within 28 days prior to first vaccine administration (JCXH-105 or Shingrix): (1) Any live vaccine, (2) Immunomodulators or immune-suppressive medication, (3) Granulocyte-macrophage colony-stimulating factor, (4) Three or more consecutive days of systemic corticosteroids. Note: subjects on stable-dose steroid replacement (for chronic disease such as iatrogenic deficiency) of prednisone ≤10 mg/day or equivalent are allowed, and (5) Other investigational agents or devices. Subjects with active or suspected immunosuppression, immunodeficiency, or autoimmune disease. Subjects receiving systemic antiviral therapy. Subjects with a positive screening test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or anti-human HIV-1 and 2 antibodies. Subjects with a positive screening test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Subjects with a known history of active or latent tuberculosis (bacillus tuberculosis).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 69 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational Product<br>Participants randomized to this arm will be given the investigational product (JCXH-105). | Biological: JCXH-105<br>* As IM injection<br>|
| Active Comparator: Active Control<br>Participants randomized to this arm will be given the FDA approved Shingrix. | Biological: Active Control (Shingrix)<br>* As IM injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAE Frequency | Frequency of SAEs characterized by type, severity, duration, and relationship to the vaccine (JCXH-105 or Shingrix) recorded from Day 1 post-vaccine administration through follow-up completion | Day 1 - Day 241 | 
| Injection site reaction | Solicited local injection site reactions characterized by frequency, severity, and duration recorded within 7 days after each vaccine administration (JCXH-105 or Shingrix) | 7 days after the first and second vaccination | 
| Solicited systemic reaction frequency | Solicited systemic adverse reactions characterized by frequency, severity, and duration recorded within 7 days after each vaccine administration (JCXH-105 or Shingrix) | 7 days after the first and second vaccination | 
| AE frequency | Adverse events (AEs) including unsolicited AEs, characterized by type, severity, duration, and relationship to the vaccine (JCXH-105 or Shingrix) recorded from Day 1 post-vaccine administration to within 30 days following each vaccine administration | 30 days after the first and second vaccination | 
| Medically attended AE frequency | Medically attended AEs (MAAEs) characterized by frequency, severity, duration, and relationship to the vaccine (JCXH-105 or Shingrix) recorded from Day 1 post-vaccine administration (JCXH-105 or Shingrix) through follow-up completion | Day 1 - Day 241 | 
| The frequency of potential immune-mediated adverse events | Potential immune-mediated disease (pIMDs) characterized by frequency, severity, duration, and relationship to the vaccine (JCXH-105 or Shingrix) recorded from Day 1 post-vaccine administration (JCXH-105 or Shingrix) through follow-up completion | Day 1 - Day 241 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cellular immunogenicity of the JCXH-105 and Shingrix vaccine | Frequency of glycoprotein E (gE)-specific CD4+ T cells expressing 2 or more markers of activation in peripheral blood mononuclear cells (PBMCs) analyzed with flow cytometry on Day 1 pre-dose (baseline) and Days 15, 31, 75, 91, and 241 (Follow-up visit) | Day 1 - Day 241 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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srRNA vaccine, Shingles vaccine, Herpes Zoster (HZ) vaccine, Healthy adult participants (aged 50 to 69 years)