V160 2-Dose and 3-Dose Regimens in Healthy Cytomegalovirus (CMV) Seronegative Females (V160-002)

Study Overview
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Brief Summary
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This study evaluated the safety, tolerability, and efficacy of the cytomegalovirus (CMV) vaccine (V160) administered in a 2-dose or 3-dose regimen to healthy seronegative women 16 to 35 years of age. Participants received blinded V160 on Day 1, Month 2, and Month 6 (3-dose regimen), V160 on Day 1 and Month 6 and placebo at Month 2 (2-dose regimen), or placebo on Day 1, Month 2, and Month 6, and were followed to approximately Month 24. The primary hypothesis of the study was that administration of a 3-dose regimen of V160 will reduce the incidence of primary CMV infection compared to placebo.

Official Title
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Double-Blind, Randomized, Placebo-Controlled Phase 2b, Multi-center Study to Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of a 2-Dose and a 3-Dose Regimen of V160 (Cytomegalovirus [CMV] Vaccine) in Healthy Seronegative Women, 16 to 35 Years of Age

Conditions
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Cytomegalovirus (CMV) Infections

Intervention / Treatment
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* Biological: V160
* Drug: 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 seronegative prior to receiving the first dose of V160/placebo Have direct exposure to young children (≤5 years of age) at home or occupationally Of childbearing potential Agrees to avoid becoming pregnant during the 6-month treatment period and for at least 4 weeks after the last dose of study drug by either 1) practicing abstinence from heterosexual activity, or 2) use a highly-effective method of birth control (as specified in the protocol) during heterosexual activity. Exclusion Criteria: Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might expose the participant to risk by participating in the trial, confound the results of the trial, or interfere with participation for the full duration of the trial, as assessed by the investigator Has history of allergic reaction or anaphylactic reaction to any vaccine component that required medical intervention or of any severe allergic reaction to any vaccine component that required medical intervention. Has a recent (<72 hours) history of febrile illness (temperature ≥100.4°F/38.0°C, oral equivalent) 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 pose more than minimal risk for the participant. A woman of childbearing potential (WOCBP) who has a positive pregnancy test at screening or within 24 hours before the first dose of study treatment. Has previously received a 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 any dose of trial vaccine. Had any inactivated vaccine administered or scheduled within the period from 14 days prior to, through 14 days following, any dose of trial vaccine. Had administration of any immune globulin or blood product within 90 days prior to injection with V160/placebo or scheduled within 30 days thereafter. 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 trial entry. 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 trial). Received any anti-viral agent with proven or potential activity against CMV two weeks prior to vaccination or is likely to receive such an agent within 2 weeks after vaccination. Receiving or has received in the year prior to enrollment immunosuppressive therapies 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 2 weeks prior to, or 2 weeks following a V160 dose. 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. Plans donation of eggs at any time from signing the informed consent through 1 month after receiving the last dose of the trial V160/placebo.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V160 3-Dose Regimen<br>Participants received 3 doses of vaccine V160 (100 Units/0.5 mL dose with Merck aluminum phosphate adjuvant [MAPA], 4°C stable formulation) administered by intramuscular (IM) injection on Day 1, Month 2, and Month 6. | Biological: V160<br>* V160 was administered as a 0.5 mL (100 Units/0.5 mL dose with Merck aluminum phosphate adjuvant [MAPA], 4°C stable formulation) IM injection.<br>* Other names: Human cytomegalovirus vaccine;|
| Experimental: V160 2-Dose Regimen<br>Participants received 2 doses of vaccine V160 (100 Units/0.5 mL dose with MAPA, 4°C stable formulation) administered IM on Day 1 and Month 6 and a placebo-saline solution at Month 2. | Biological: V160<br>* V160 was administered as a 0.5 mL (100 Units/0.5 mL dose with Merck aluminum phosphate adjuvant [MAPA], 4°C stable formulation) IM injection.<br>* Other names: Human cytomegalovirus vaccine;Drug: Placebo<br>* Saline solution administered as a 0.5 mL IM injection<br>|
| Placebo Comparator: Placebo<br>Participants received placebo (saline solution) by IM injection on Day 1, Month 2, and Month 6. | Drug: Placebo<br>* Saline solution 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 |
| --- | --- | --- |
| Number of Participants Who Became Infected With Wild-Type Cytomegalovirus Infection Starting at 4 Weeks Post Last Dose (V160 3-dose Regimen Group and Placebo Group) | Cytomegalovirus infection (CMVi) was defined as the detection of wild-type cytomegalovirus (CMV) (non vaccine type) by polymerase chain reaction in a single saliva or urine sample in a previously CMV-uninfected participant. CMVi cases in the 3-dose regimen and placebo groups were reported and incidence rate (per 100 person-years) calculated based on follow-up time starting at 4 weeks post last dose (Month 7) through approximately Month 24 (or time point to reach required cases for assessment). The percent reduction in CMVi incidence rate in the 3-dose regimen group compared to the placebo group was assessed. | 4 weeks post last vaccination (Month 7) up to  Month 24 | 
| Number of Participants With Solicited Injection-site Adverse Events | An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. Following vaccination with V160 or placebo, the number of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were redness/erythema, swelling, and pain. | Up to 5 days after each vaccination | 
| Number of Participants With Solicited Systemic AEs | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. Following vaccination with V160 or placebo, the number of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were fatigue, joint pain/arthralgia, muscle pain/myalgia, and headache. | Up to 14 days after each vaccination | 
| Number of Participants With Vaccine-related Serious Adverse Events | A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator. Following vaccination with V160 or placebo, the number of participants with vaccine-related serious adverse events was assessed. | Up to 14 days after each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Became Infected With Wild-Type CMV Infection Starting at 4 Weeks Post Last Dose (V160 2-dose Regimen Group and Placebo Group) | CMVi is defined as detection of wild-type CMV (non-vaccine type) by polymerase chain reaction in a single saliva or urine sample in a previously CMV-uninfected participant. CMVi cases in the 2-dose regimen and placebo groups were reported and incidence rate (per 100 person-years) calculated based on follow-up time starting at 4 weeks post last dose (Month 7) through approximately Month 24 (or time point to reach required cases for assessment). The percent reduction in CMVi incidence rate in the 2-dose regimen group compared to the placebo group was assessed. | 4 weeks post last vaccination (Month 7) up to  Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention of cytomegalovirus infection (CMVi)