Study to Evaluate Safety, Tolerability, and Immunogenicity of Candidate Human Cytomegalovirus Vaccine in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety and effectiveness of four different doses of cytomegalovirus vaccines in healthy adults.

Detailed Description
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This study is designed to assess safety and immunogenicity of four dose formulations of cytomegalovirus (CMV) vaccine (0.5 μg gB content with aluminum phosphate (alum), 1.0 μg glycoprotein B (gB) content with alum, 2.0 μg gB content with alum, or 1.0 μg gB content (without alum) as compared with placebo in approximately 125 healthy CMV-seronegative volunteer participants between 18 and 40 years of age.

Official Title
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A Phase 1 Randomized, Observer-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability, and Immunogenicity of the Candidate Human Cytomegalovirus Vaccine (VBI-1501) in Healthy Adults

Conditions
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Cytomegalovirus Infections

Intervention / Treatment
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* Drug: VBI-1501A 0.5 μg
* Drug: VBI-1501A 1.0 μg
* Drug: VBI-1501A 2.0 μg
* Drug: VBI-1501 1.0 μg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy adult female and male 18 to 40 years of age, inclusive; Serologically confirmed to be CMV seronegative at screening; Female volunteers must agree to use an adequate contraception method as deemed appropriate by the investigator Sign an informed consent document indicating understanding of the purpose and procedures required for the study and willingness to participate in the study Exclusion Criteria: History of or current clinically significant medical illness or any other illness that in the opinion of the investigator interferes with the interpretation of the study results Clinically significant abnormal physical examination, vital signs, or clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening as determined by the investigator Previous receipt of any cytomegalovirus vaccine History of allergic reactions or anaphylactic reaction to any vaccine component Pregnant or breastfeeding or plans to conceive from two weeks before the study start through six months after the last dose of study vaccine Known or suspected impairment of immunological function, including but not limited to autoimmune diseases, splenectomy, or HIV/AIDS Chronic administration (defined as more than 14 days in total) of immune-suppressive or other immune-modifying drug with six months prior to the product dose (for corticosteroids, this is defined as prednisone ≥20 mg/day or equivalent). Inhaled and topical steroids are allowed Participation in another clinical study within 30 days or plans to participate in another treatment based clinical study during the conduct of the present study Any skin abnormality or tattoo that would limit post-vaccination injection site assessment Any history of cancer requiring chemotherapy or radiation within 5 years of randomization or current disease Are family members of study center staff

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VBI-1501A: 0.5µg with adjuvant<br>0.5µg CMV vaccine with adjuvant | Drug: VBI-1501A 0.5 μg<br>* VBI-1501A: 0.5 μg with alum-administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168<br>|
| Experimental: VBI-1501A: 1.0µg with adjuvant<br>1.0µg CMV vaccine with adjuvant | Drug: VBI-1501A 1.0 μg<br>* VBI-1501A: 1.0 μg with alum with alum-administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168<br>|
| Experimental: VBI-1501A: 2.0 µg with adjuvant<br>2.0 µg CMV vaccine with adjuvant | Drug: VBI-1501A 2.0 μg<br>* VBI-1501A: 2.0 μg with alum-administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168<br>|
| Experimental: VBI-1501: 1.0µg without adjuvant<br>1.0µg CMV vaccine without adjuvant | Drug: VBI-1501 1.0 μg<br>* VBI-1501: 1.0 μg without alum-administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168<br>|
| Placebo Comparator: Placebo<br>Buffer/sucrose used for VBI-1501 suspension | Drug: Placebo<br>* buffer/sucrose used for VBI-1501 suspension- administered as a 0.5 mL intramuscular injection on Days 0, 56, and 168.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Local and Systemic Adverse Events During Seven-Day Follow-Up Period |  | Day of vaccine administration (days 0, 56, 168) and six subsequent days | 
| Number of Participants With Any Adverse Event |  | Following each of the 3 injections of study vaccine, the occurrence of adverse events was captured during a 28-day follow-up period as well as through Day 336 or early withdrawal. | 
| Number of Participants With Any Serious Adverse Event |  | Through Day 336 or early withdrawal | 
| Number of Participants With Any Hematological or Biochemical Laboratory Abnormality | Blood and urine samples were collected at screening for all evaluations with additional blood samples obtained on Days 28, 56, 84, 168, 196, 280, and 336. The following clinical laboratory evaluations were performed: Biochemistry: alanine aminotransferase; aspartate aminotransferase; creatinine; blood urea nitrogen; Hematology: neutrophils, lymphocytes, eosinophils, hemoglobin, platelet count, white blood cell count; Infection status: HIV, hepatitis B, hepatitis C, and cytomegalovirus; and Urinalysis: blood, glucose, protein. | Through Day 336 or early withdrawal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer of Antibody Binding to CMV gB |  | Through Day 336 or early withdrawal | 
| Geometric Mean Titer of Antibody Avidity Index Value Against gB | To measure the avidity of responses against CMV gB protein, a standard ELISA assay using recombinant gB protein which did or did not include treatment with 5M urea for 30 minutes of samples after sera had been incubated with recombinant protein. The reported value, or Avidity Index, represents the percent of signal measured in ELISA after treatment with urea relative to samples not exposed to urea. | Through Day 336 or early withdrawal | 
| Geometric Mean Titer of Neutralizing Antibody Against CMV Infection of Fibroblast Cells |  | Through Day 196 or early withdrawal | 
| Geometric Mean Titer of Neutralizing Antibody Against CMV Infection of Epithelial Cells |  | Through Day 336 or early withdrawal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, VBI-1501A, VBI-1501, prophylactic vaccine, virus diseases, cytomegalovirus (CMV), cytomegalovirus infections, cytomegalovirus vaccines, Herpesviridae Infections, Human Herpesvirus 5 (HHV5), Vaccines, virus-like particle (VLP), enveloped virus-like particle (eVLP)