Safety and Immunogenicity of the Human Cytomegalovirus (CMV) Vaccine (V160) in Healthy Japanese Men (V160-003)

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety and tolerability of a 3-dose regimen of V160 administered by intramuscular (IM) injection in healthy Japanese male participants by cytomegalovirus (CMV) serostatus. There is no formal hypothesis.

Official Title
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A Phase I Randomized, Double-Blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Immunogenicity of V160 (Human Cytomegalovirus Vaccine) in Healthy Japanese Men

Conditions
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Cytomegalovirus Infections

Intervention / Treatment
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* Biological: V160
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy based on medical history and physical examination Serologically confirmed to be CMV seropositive or CMV seronegative at Visit 1 If of reproductive potential, agrees to the following from randomization through at least 4 weeks after the last dose of V160-/placebo (from Day 1 through Month 7): 1) practice abstinence from heterosexual activity and remain abstinent, or 2) use contraception unless confirmed to be azoospermic as detailed in the protocol Exclusion Criteria: History of any allergic reaction or anaphylactic reaction to any vaccine component that required medical intervention Plans donation of sperm any time from signing the informed consent through 1 month after receiving the last dose of study drug Is currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition that requires immunosuppressive medication. Has a condition in which repeated venipuncture or injections post more than minimal risk for the participant, such as hemophilia, thrombocytopenia, other severe coagulation disorders, or significantly impaired venous access Has major psychiatric illness including: any history or schizophrenia or severe psychosis, bipolar disorder requiring therapy, or suicidal ideation within 3 years. Has previously received any CMV vaccine Had any live virus vaccine administered or scheduled to be administered in the period from 4 weeks prior to, and 4 weeks following receipt of study drug Had any inactivated vaccine administered or scheduled within the period from 14 days prior to, through 14 days following study drug Had administration of any immune globulin or blood product within 90 days prior to injection with study drug or scheduled within 30 days thereafter Has received systemic corticosteroids (equivalent of ≥2 mg/kg total daily dose of prednisone or ≥20 mg/d for persons weighing >10 kg) for ≥14 consecutive days and has not completed treatment at least 30 days prior to study entry Has received systemic corticosteroids exceeding physiologic replacement doses (≈5 mg/d prednisone equivalent) within 14 days prior to the first vaccination (participants using inhaled, nasal, or topical steroids are considered eligible for the study) Has received any anti-viral agent (e.g. letermovir, ganciclovir, valganciclovir, foscarnet, and valacyclovir) with proven or potential activity against CMV 14 days prior to vaccination or is likely to receive such an agent within 14 days after vaccination Receiving or has received in the year prior to enrollment immunosuppressive therapies including but not limited to rapamycin (also sirolimus), tacrolimus (also FK-506), or other therapies used for solid organ/cell transplant, radiation therapy, immunosuppressive/cytotoxic immunotherapy, chemotherapy and other immunosuppressive therapies known to interfere with the immune response. Topical tacrolimus is allowed provided that it is not used within 14 days prior to, or 14 days following study drug Has participated in another clinical trial in the past 4 weeks, or plans to participate in a treatment-based trial or a trial in which an invasive procedure is to be performed while enrolled in this trial.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V160<br>Participants will receive V160 vaccination by IM injection on Day 1, Month 2, and Month 6. | Biological: V160<br>* V160 administered as a 0.5 mL (100 Units) IM injection containing 225 mcg aluminum phosphate adjuvant (APA)<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo by IM injection on Day 1, Month 2, and Month 6. | Other: Placebo<br>* Saline solution (0.9% sodium chloride [NaCl] administered as a 0.5 mL IM injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Solicited Injection-site Adverse Event (AE) | Participants used the vaccination report card (VRC) to document the presence of any solicited injection-site AEs (pain/tenderness, erythema/redness, and swelling) that occurred in the 5 days after each vaccination. The percentage of participants with a solicited injection-site AE was reported. | Up to 5 days after each vaccination | 
| Percentage of Participants With a Solicited Systemic Adverse Event (AE) | Participants used the vaccination report card (VRC) to document the presence of any solicited systemic AEs (headache, fatigue, muscle pain, joint pain) that occurred in the 14 days after each vaccination. The percentage of participants with a solicited systemic AE is reported. | Up to 14 days after each vaccination | 
| Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE) | An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical event. The percentage of participants with an SAE considered to be at least possibly related to the study intervention will be reported | Up to 14 days after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of CMV-specific Neutralizing Antibody (NAb) | The NAb GMT in initially CMV-seronegative participants vaccinated with a 3-dose regimen of V160 administered IM was assessed. | 1 month after third vaccination (at 7 months) | 
| Number of Participants With Viral Detection of V160 in Plasma | The number of participants with positive viral detection in plasma (defined by viral load in plasma ≥assay defined threshold cutoff value) was assessed. | Day 1 (predose, at dosing, and 3 hours postdose), Day 3, Day 7, and Day 14 | 
| Number of Participants With Wild-Type CMV Detection in Urine and Saliva | The number of participants with positive wild-type viral shedding in urine or saliva (defined by viral load in saliva/urine ≥ assay defined threshold cutoff value) will be assessed. | Day 1 (predose), 3, 7, and 14 and Months 2, 6, and 7 | 
| Number of Participants With Viral Detection of V160 in Injection-site Swab and Adhesive Tape Swab | The number of participants with positive viral leakage in injection-site swab and adhesive tape swab (defined by viral load in injection-site swab/adhesive tape swab ≥ assay defined threshold cutoff value) will be assessed. | Day 1: 0, 10, 20, and 30 minutes postvaccination |