Safety and Immunogenicity of CRV-101 Vaccine for the Prevention of Herpes Zoster in Adults Aged 50 Years and Older

NCT05304351 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CRV-101-101
• Study Type: interventional
• Target: 1,516
• Locations: 1 country
• Sites: 14

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

Conditions

Herpes Zoster; Shingles

Keywords

Herpes Zoster; Shingles; Varicella Zoster Virus; Vaccine

Outcome Measures

Primary Outcomes (9)

• Occurrence of solicited local and systemic signs and symptoms

  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)

  Day 0-Day 6 for each vaccination timepoint

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

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

  Day 0-Day 6 for each vaccination timepoint

• Occurrence of unsolicited non-serious adverse events

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

  Day 0-Day 28 following each vaccination

• Occurrence of serious adverse events (SAEs)

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

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

• Occurrence of adverse events (AEs) of special interest

  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 \[Month 14\])

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

• To evaluate safety as measured by hematology and biochemistry parameters

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

  Day 7 and Day 63

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

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

  Month 3

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

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

  Month 3

• To compare the humoral immune response of Shingrix® to amezosvatein

  Comparison of humoral response between amezosvatein and Shingrix at Month 3

  Month 3

Secondary Outcomes (6)

• 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

Other Outcomes (11)

• Vaccine protein-specific antibody concentrations elicited by response to vaccination for durability post Month 3

  Month 14, and LTFU up to 5 additional years.

• Fold rise of vaccine protein-specific antibody concentrations elicited in response to vaccination post Month 3

  Month 14, and LTFU up to 5 additional years.

• Frequency of vaccine protein-specific CD4+ T cells expressing at least 2 activation markers in response to vaccination for durability post Month 3

  Month 0, Month 14, and in LTFU up to 5 additional years.

Study Arms (13)

Arm A

EXPERIMENTAL

Investigational Vaccine

Biological: Amezosvatein Antigen High Dose Arm A

Arm B

EXPERIMENTAL

Investigational Vaccine

Biological: Amezosvatein Antigen Low Dose Arm B

Arm C

ACTIVE COMPARATOR

Active comparator

Biological: Shingrix

Arm D

EXPERIMENTAL

Investigational Vaccine

Biological: Amezosvatein Adjuvant Dose Arm D

Arm E

ACTIVE COMPARATOR

Active Comparator

Biological: Shingrix

Arm F

EXPERIMENTAL

Investigational Vaccine

Biological: Amezosvatein Adjuvant Dose Arm F

Arm G

ACTIVE COMPARATOR

Active Comparator

Biological: Shingrix

Arm H

EXPERIMENTAL

Investigational Vaccine

Biological: Amezosvatein Adjuvant Dose Arm H

I

ACTIVE COMPARATOR

Active Comparator

Biological: Shingrix

Arm J

EXPERIMENTAL

Investigational Vaccine

Biological: Amezosvatein Adjuvant Dose Arm J

Arm K

ACTIVE COMPARATOR

Active Comparator

Biological: Shingrix

Arm L

EXPERIMENTAL

Investigational Vaccine

Biological: Amezosvatein Adjuvant Dose Arm L

Arm M

ACTIVE COMPARATOR

Active Comparator

Biological: Shingrix

Interventions

Amezosvatein Antigen High Dose Arm A BIOLOGICAL

Suspension for injection administered intramuscularly (IM) in the deltoid region of the non-dominant arm in Month 0 and Month 2 per study schedule

Arm A

Amezosvatein Antigen Low Dose Arm B BIOLOGICAL

Suspension for injection administered intramuscularly (IM) in the deltoid region of the non-dominant arm in Month 0 and Month 2 per study schedule

Arm B

Shingrix BIOLOGICAL

Suspension for injection administered intramuscularly (IM) in the deltoid region of the non-dominant arm in Month 0 and Month 2 per study schedule

Arm C; Arm E; Arm G; Arm K; Arm M; I

Amezosvatein Adjuvant Dose Arm D BIOLOGICAL

Suspension for injection administered intramuscularly (IM) in the deltoid region of the non-dominant arm in Month 0 and Month 2 per study schedule

Arm D

Amezosvatein Adjuvant Dose Arm F BIOLOGICAL

Suspension for injection administered intramuscularly (IM) in the deltoid region of the non-dominant arm in Month 0 and Month 2 per study schedule

Arm F

Amezosvatein Adjuvant Dose Arm H BIOLOGICAL

Suspension for injection administered intramuscularly (IM) in the deltoid region of the non-dominant arm in Month 0 and Month 2 per study schedule

Arm H

Amezosvatein Adjuvant Dose Arm J BIOLOGICAL

Suspension for injection administered intramuscularly (IM) in the deltoid region of the non-dominant arm in Month 0 and Month 2 per study schedule

Arm J

Amezosvatein Adjuvant Dose Arm L BIOLOGICAL

Suspension for injection administered intramuscularly (IM) in the deltoid region of the non-dominant arm in Month 0 and Month 2 per study schedule

Arm L

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Male and non-pregnant female participant must be ≥50 years of age inclusive, at the time of signing the informed consent.
• Arms A, B, C, J, K, L, and M will enroll participants ≥50 years of age
• Arms D, E, F, G, H, and I will enroll participants ≥50 to \<70 years of age
• Participants who are healthy as determined by medical evaluation including comprehensive medical history, comprehensive physical examination, vital signs\*, and screening laboratory tests conducted no more than 30 days prior to first study injection administration (Day 0).
• Vital signs within grade 1 on the severity grading scale, excluding temperature, are allowed. If vital sign parameter meets grade 2 criteria, then subject must be excluded. Vital signs may be repeated 3 times after a period of rest as needed if transient abnormal fluctuation is suspected.
• (Applicable only for arms A through I) Completed an Emergency Use Authorization (EUA) or Conditional Marketing Authorization or licensed initial COVID-19 vaccine series (as applicable) ≥30 days prior to enrollment (i.e., at least 30 days prior to the Day 0 visit).
• Screening laboratory values \[sodium, potassium, blood urea nitrogen (BUN), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), total bilirubin, alkaline phosphatase, creatinine, random glucose, white blood cell count with differential, hemoglobin, and platelet count\] must be within normal ranges or considered not clinically significant by the PI.\*\*
• Negative HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody at screening. If HIV 1/2 antibody is positive, and confirmation testing is negative the participant may be enrolled.
• Normal urinalysis or, if abnormal, urinalysis determined to be not clinically significant by the PI at screening.\*\*
• Screening laboratory values that are abnormal but are considered abnormal due to an acute illness or process may be repeated once. Careful consideration regarding enrolling subjects with screening lab values meeting grade 2 severity that are considered not clinically significant must be made as there is less room for fluctuations to increase to gr ade 3 (severe) lab events.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
• Is a woman of nonchildbearing potential (WONCBP). OR
• Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as defined below during the 30 days prior to Day 0 (i.e., the first study vaccine) and is willing to continue to do so during the study until at least 90 days after the last dose of study vaccine, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relation to the timing of the first dose of study vaccine.
• A WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the day of each study vaccine (prior to vaccination). If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• History of herpes zoster (shingles).
• History or presence of acute or chronic illness (including cardiovascular, pulmonary, neurological, hepatic, rheumatic, hematological, metabolic, gastrointestinal, endocrinologic or renal disorders, or uncontrolled hypertension) which in the opinion of the Principal Investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
• History of autoimmune disease or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, HIV infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders) that is likely to affect the immune response to vaccination as determined by the PI.
• Rash, tattoos, or any other dermatological condition that could adversely affect the vaccine injection site or interfere with its evaluation.
• Abnormal blood pressure \>150 mm Hg systolic or \>95 mm Hg diastolic prior to first study injection administration (Day 0).\*\*\*
• \*\*\* If abnormal, BP may be repeated up to 3 times after a rest period of 5 minutes between each measurement.
• History of significant psychiatric illness (including history of suicidal ideation or attempt) with or without current medication.
• Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to less than 4 years).
• Acute disease and/or fever at the time of enrollment (Day 0).
• Fever is defined as body temperature ≥38 °C (100.4 °F); oral acquisition will be the preferred route for recording temperature throughout this study.
• Participants with a minor illness (such as mild diarrhea or mild upper respiratory infection) without fever may be enrolled after resolution of the minor illness, at the discretion of the investigator.
• Immunized with a vaccine against herpes zoster (Zostavax®, Shingrix®, other licensed or investigational HZ vaccine).
• Prior varicella vaccination at any time.
• Received any vaccine within 30 days prior to enrollment (Day 0) or received any non-investigational immunizations while on study except for seasonal influenza, pneumococcal vaccines, other vaccines per the ACIP recommendations, or any licensed or emergency use authorization or conditional marketing authorized COVID-19 booster. Administration of these immunizations must not occur until 30 days after the final study vaccination and completion of the Day 84 immunology blood draw and must not occur within the 30 days prior to each on-study immunology blood draw after Day 84. Receipt of any VZV vaccine is prohibited on the study.

Sponsors & Collaborators

• Curevo Inc: lead

Study Sites (14)

Curevo Investigational Site

Tempe, Arizona, 85281, United States

Location

Curevo Investigational Site

Coral Gables, Florida, 33134, United States

Location

Curevo Investigational Site

Tampa, Florida, 33616, United States

Location

Curevo Investigational Site

Oak Brook, Illinois, 60523, United States

Location

Curevo Investigational Site

Lenexa, Kansas, 66219, United States

Location

Curevo Investigational Site

Newton, Kansas, 67114, United States

Location

Curevo Investigational Site

Lexington, Kentucky, 40509, United States

Location

Curevo Investigational Site

Las Vegas, Nevada, 89119, United States

Location

Curevo Investigational Site

Edmond, Oklahoma, 73013, United States

Location

Curevo Investigational Site

Knoxville, Tennessee, 37909, United States

Location

Curevo Investigational Site

Austin, Texas, 78745, United States

Location

Curevo Investigational Site

Dallas, Texas, 75251, United States

Location

Curevo Investigational Site

Euless, Texas, 76040, United States

Location

Curevo Investigational Site

Salt Lake City, Utah, 84107, United States

Location

MeSH Terms

Conditions

Herpes Zoster; Chickenpox

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Lisa Shelton, ARNP

  Curevo Inc

  STUDY DIRECTOR

• Guy De La Rosa, MD

  Curevo Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: March 31, 2022
• Study Start: February 2, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): March 6, 2032
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)