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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 2,200
- 试验地点
- 95
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 16 Years 至 35 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
V160 3-Dose Regimen
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.
干预措施: V160 (Biological)
V160 2-Dose Regimen
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.
干预措施: V160 (Biological)
V160 2-Dose Regimen
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.
干预措施: Placebo (Drug)
Placebo
Participants received placebo (saline solution) by IM injection on Day 1, Month 2, and Month 6.
干预措施: Placebo (Drug)
结局指标
主要结局
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)
时间窗: 4 weeks post last vaccination (Month 7) up to ~Month 24
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.
Number of Participants With Solicited Injection-site Adverse Events
时间窗: Up to 5 days after each vaccination
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.
Number of Participants With Solicited Systemic AEs
时间窗: Up to 14 days after each vaccination
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.
Number of Participants With Vaccine-related Serious Adverse Events
时间窗: Up to 14 days after each vaccination
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.
次要结局
- 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)(4 weeks post last vaccination (Month 7) up to ~Month 24)