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Clinical Trials/NCT05304351
NCT05304351
Active, not recruiting
Phase 2

A Randomized, Observer-Blind, Phase 2 Study To Assess the Safety and Immunogenicity of CRV-101 Vaccine Head-To-Head With SHINGRIX® for the Prevention of Herpes Zoster in Adults Aged 50 Years and Older

Curevo Inc1 site in 1 country1,516 target enrollmentFebruary 2, 2022

Overview

Phase
Phase 2
Intervention
Amezosvatein Antigen High Dose Arm A
Conditions
Herpes Zoster
Sponsor
Curevo Inc
Enrollment
1516
Locations
1
Primary Endpoint
Occurrence of serious adverse events (SAEs)
Status
Active, not recruiting
Last Updated
7 months ago

Overview

Brief Summary

The purpose of this study is to assess the safety and immunogenicity of amezosvatein (CRV-101), an investigational vaccine compared to Shingrix® for the prevention of herpes zoster in adults aged 50 years and older

Detailed Description

In the first part of the trial, participants will be randomized 1:1:1 to amezosvatein high antigen dose (Arm A), amezosvatein low antigen dose (B), or Shingrix (C). In the second part of the trial, participants will be randomized 5:1 to receive amezosvatein adjuvant dose D or Shingrix (E), adjuvant dose F or Shingrix (G), or adjuvant dose H or Shingrix (I). In the third part of the trial, participants will be randomized 3:1 to receive amezosvatein adjuvant dose J or Shingrix (K) or amezosvatein adjuvant dose L or Shingrix (M). Both study vaccines, amezosvatein and Shingrix, will be administered by intramuscular injection on Month 0 and Month 2. Safety, reactogenicity, and immunogenicity analysis will be performed overall and by age group. Participants will be followed for safety, immunogenicity, and herpes zoster cases from Day 0 to the main study end (Month 14), and through the long-term follow up (LTFU) extension period of up to 5 additional years.

Registry
clinicaltrials.gov
Start Date
February 2, 2022
End Date
March 6, 2032
Last Updated
7 months ago
Study Type
Interventional
Study Design
Parallel
Sex
All

Investigators

Sponsor
Curevo Inc
Responsible Party
Sponsor

Eligibility Criteria

Inclusion Criteria

  • Not provided

Exclusion Criteria

  • Not provided

Arms & Interventions

Arm A

Investigational Vaccine

Intervention: Amezosvatein Antigen High Dose Arm A

Arm B

Investigational Vaccine

Intervention: Amezosvatein Antigen Low Dose Arm B

Arm C

Active comparator

Intervention: Shingrix

Arm D

Investigational Vaccine

Intervention: Amezosvatein Adjuvant Dose Arm D

Arm E

Active Comparator

Intervention: Shingrix

Arm F

Investigational Vaccine

Intervention: Amezosvatein Adjuvant Dose Arm F

Arm G

Active Comparator

Intervention: Shingrix

Arm H

Investigational Vaccine

Intervention: Amezosvatein Adjuvant Dose Arm H

I

Active Comparator

Intervention: Shingrix

Arm J

Investigational Vaccine

Intervention: Amezosvatein Adjuvant Dose Arm J

Arm K

Active Comparator

Intervention: Shingrix

Arm L

Investigational Vaccine

Intervention: Amezosvatein Adjuvant Dose Arm L

Arm M

Active Comparator

Intervention: Shingrix

Outcomes

Primary Outcomes

Occurrence of serious adverse events (SAEs)

Time Frame: Day 0 - Day 421 [Month 14] (as noted in description)

Occurrence and relationship to vaccination of all serious adverse events (SAE) from after first vaccination (Day 0) to main study end (Day 421 \[Month 14\])

Occurrence of solicited local and systemic signs and symptoms

Time Frame: Day 0-Day 6 for each vaccination timepoint

Occurrence, severity, and duration of solicited local injection site reactions within 7 days (Day 0-Day 6) following each vaccination. (i.e., pain, redness, swelling) Occurrence, severity, and duration of solicited systemic reactions within 7 days (Day 0-Day 6) following each vaccination. (i.e., myalgia, fatigue, headache, chills, fever)

To compare the reactogenicity of amezosvatein to that of the standard 2-dose schedule of Shingrix®

Time Frame: Day 0-Day 6 for each vaccination timepoint

Comparison of the proportion of participants reporting solicited local and systemic reactogenicity events following each vaccination

Occurrence of unsolicited non-serious adverse events

Time Frame: Day 0-Day 28 following each vaccination

Occurrence, severity, and relationship to vaccination of unsolicited adverse events within 29 days (Day 0-Day 28) following each vaccination

Occurrence of adverse events (AEs) of special interest

Time Frame: Day 0 - Day 421 [Month 14] (as noted in description)

Occurrence of any Potential Immune-Mediated Medical Conditions (PIMMCs) from post first vaccination (Day 0) to main study end (Day 421 \[Month 14\]) Medically attended adverse events (MAAEs) from post first vaccination (Day 0) to study end (Day 421 \[Month 14\])

To evaluate safety as measured by hematology and biochemistry parameters

Time Frame: Day 7 and Day 63

Occurrence, intensity, and relationship to vaccination of clinically significant hematologic and biochemical adverse events at at Day 7 and Day 63

Vaccine protein-specific antibody concentrations (GMC) elicited by vaccination between Month 0 and Month 3

Time Frame: Month 3

Assess humoral immune response as determined by Enzyme-linked Immunosorbent Assay (ELISA)

Vaccine Response Rate (≥ 4 fold increase in antibody concentration from pre-vaccination) at Month 3 for arms A, B, and C

Time Frame: Month 3

• Assess humoral immune response as determined by Enzyme-linked Immunosorbent Assay (ELISA)

To compare the humoral immune response of Shingrix® to amezosvatein

Time Frame: Month 3

Comparison of humoral response between amezosvatein and Shingrix at Month 3

Secondary Outcomes

  • Fold rise of vaccine protein-specific antibody concentrations elicited in response to vaccination for durability post Month 3(Month 3)
  • Anti-Varicella Zoster Virus (VZV) neutralizing antibody titer in response to vaccination between Day 0 and Month 3 for arms A, B, and C(Month 3)
  • Frequency of vaccine protein-specific CD4+ T cells expressing at least 2 activation markers in response to vaccination between Month 0 and Month 3 for arms A, B, and C(Month 3)
  • To compare the frequency of vaccine protein-specific CD4+ T cells expressing at least 2 activation markers of Shingrix® to amezosvatein between Month 0 and Month 3 for arms A, B, and C.(Month 3)
  • CMI Vaccine Response rate (≥ 2-fold increase in the frequency of vaccine protein-specific CD4+ T cell expressing at least 2 activation markers) at Month 3 for arms A, B, and C.(Month 3)
  • Vaccine Response Rate (≥ 4 fold increase in antibody concentration from pre-vaccination) at Month 3 for arms D through M(Month 3)

Study Sites (1)

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Curevo's Amezosvatein Shows Sustained Immunogenicity and Improved Tolerability in Phase 2 Shingles Vaccine Trial- Curevo's amezosvatein maintained non-inferior anti-gE antibody levels compared to Shingrix one year after the second dose in adults aged 50-69. - The Phase 2 trial (NCT05304351) demonstrated that amezosvatein had a statistically significant improvement in Grade 2 and 3 reactogenicity versus Shingrix. - No confirmed shingles cases were observed in the highest antigen dose arms of amezosvatein or the Shingrix arm during the post-hoc analysis. - Curevo plans to advance amezosvatein into global Phase 3 trials in 2025, targeting the multi-billion dollar shingles vaccine market.Curevo's Amezosvatein Shows Zero Shingles Cases in Phase 2 Trial- Curevo's amezosvatein vaccine demonstrated zero confirmed cases of shingles in a Phase 2 trial after 18.8 months of follow-up, contrasting with an expected 10 cases without vaccination. - The Phase 2 trial (NCT05304351) compared amezosvatein head-to-head against Shingrix in 876 participants aged 50 and older, showing comparable safety profiles between the two vaccines. - Amezosvatein exhibited a statistically significant improvement in Grade 2 and Grade 3 reactogenicity compared to Shingrix, potentially improving vaccine accessibility and reducing hesitancy. - The highest dose of amezosvatein met the co-primary immunogenicity endpoint, demonstrating non-inferior immune responses to Shingrix, with similar serum neutralizing antibodies to VZV.Curevo's Amezosvatein Shows Promise in Phase 2 Trial with Improved Tolerability for Shingles Vaccine- Curevo Vaccine's amezosvatein demonstrated non-inferiority to Shingrix in a Phase 2 trial, meeting all primary endpoints for immunogenicity. - The trial, involving 876 participants, showed amezosvatein had a 100% vaccine response rate compared to Shingrix's 97.9%. - Amezosvatein exhibited lower rates of local and systemic adverse events, suggesting improved tolerability over the existing Shingrix vaccine. - Curevo plans to advance amezosvatein into global Phase 3 trials in 2024, targeting the $4 billion shingles vaccine market.