A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity of the Human Cytomegalovirus Vaccine (V160) in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 190
- 主要终点
- Percentage of Participants With an Injection-site AE
研究概览
简要总结
This study will evaluate the safety, tolerability, and immunogenicity of various doses, formulations, and routes of administration of Human Cytomegalovirus (HCMV) vaccine V160 administered in a 3-dose regimen in healthy adults. The initial treatment arm of HCMV seropositive participants will receive V160 Low Dose without adjuvant by intramuscular injection. Escalation of the V160 dose, inclusion of adjuvant, administration by intradermal injection, and vaccination of HCMV seronegative participants will be performed only after review of safety data of previous treatment arms. The purpose of the study is to identify vaccine formulations associated with optimal safety profile and HCMV-specific immune response for evaluation in subsequent clinical studies of V160.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy based on medical history and physical examination
- •Serologically confirmed to be HCMV seronegative or HCMV seropositive
- •Agrees to avoid unusual, unaccustomed strenuous, vigorous physical exercise/activity from 72 hours before through 72 hours after each dose of study vaccine
- •Body weight ≥110 lbs (50 kg) and body mass index (BMI) of 19 to 32 kg/m^2
- •If of reproductive potential, agrees to the following during the study and for 4 weeks after the last dose of study vaccine: 1) practice abstinence from heterosexual activity, or 2) use or have their partner use 2 allowable methods of birth control during heterosexual activity
排除标准
- •Has previously received any cytomegalovirus vaccine
- •Has history of allergic reaction or anaphylactic reaction to any vaccine component that required medical intervention
- •Has history of any severe allergic reaction that required medical intervention
- •Is pregnant or breastfeeding or expecting to conceive from 2 weeks before the study through 1 month after the last dose of study vaccine
- •Plans to donate eggs or sperm from study start through 1 month after the last dose of study drug
- •Has impairment of immunologic function including, but not limited to autoimmune disease, splenectomy, or human immunodeficiency virus acquired immunodeficiency syndrome (HIV/AIDS)
- •Received systemic corticosteroids for ≥14 consecutive days and has not completed treatment within 30 days of study start
- •Received immunosuppressive therapy including, but not limited to rapamycin and equivalents, tacrolimus, FK-506, fujimycin, or other therapies used for solid organ/cell transplant, radiation therapy, immunosuppressive/cytotoxic chemotherapy, or other therapy known to interfere with the immune response within 1 year of study start
- •Has a condition in which repeated venipuncture or injections pose more than minimal risk, such as hemophilia, thrombocytopenia or other severe coagulation disorders, or significantly impaired venous access
- •Has a condition that requires active medical intervention or monitoring such as diabetes mellitus, autoimmune disease, or a clinically significant chronic medical condition that is considered progressive
- •Has history within the past 5 years or current drug or alcohol abuse
- •Has major psychiatric illness
- •Is legally or mentally incapacitated
- •Has participated in another clinical study in the past 4 weeks, or plans during the present study to participate in a treatment-based study or a study in which an invasive procedure is performed
- •Has received valganciclovir, ganciclovir, valacyclovir, foscarnet, or cidofovir from 4 weeks prior to 1 month following each V160 vaccination
结局指标
主要结局
Percentage of Participants With an Injection-site AE
时间窗: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
Injection-site AEs are defined as redness, swelling, and pain/tenderness.
Percentage of Participants With a Serious Adverse Event (SAE)
时间窗: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
A serious adverse event is any adverse event occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event
Percentage of Participants With a Systemic AE
时间窗: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
A Systemic AE includes, but is not exclusive of, the following AEs: fatigue, myalgia, headache and joint pain
Percentage of Participants With an Adverse Event (AE)
时间窗: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Percentage of Participants With a Serious Vaccine-Related Adverse Event
时间窗: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
A serious adverse event is any adverse event occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. A serious vaccine-related adverse event was determined by the investigator to be related to the vaccine.
Percentage of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to Month 6
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Percentage of Participants With Events of Clinical Interest (ECI)
时间窗: Up to 18 months
An event of clinical interest (ECI) is identified as any overdose, elevated liver values meeting threshold criteria (aspartate aminotransferase or alanine aminotransferase ≥3x upper limit of normal (ULN); total bilirubin ≥2x ULN, and, at the same time, alkaline phosphatase \<2xULN). Additionally, confirmed, diagnosed autoimmune conditions are considered ECIs.
Geometric Mean Titer of HCMV-specific Neutralizing Antibody After Vaccination 3
时间窗: Month 7 (1 month after vaccination 3 at Month 6)
Serum samples for measuring neutralizing antibodies using the Merck Neutralizing Antibody (NAb) assay were collected at month 7. The LiCor-based near-infrared dye (NIRDye) In-Cell Western (ICW) HCMV microneutralization assay was used to detect and quantify anti-HCMV neutralizing antibodies. The primary hypothesis was that for HCMV-seronegative participants, at least 1 of the vaccination groups receiving V160 formulated with or without adjuvant would exhibit higher HCMV-specific neutralizing antibody titers than the placebo group.
次要结局
- Geometric Mean Concentration of Interferon-Gamma After Stimulation of Whole Blood Sample With Pooled HCMV Antigen Peptides(Month 7 (1 month after vaccination 3 at Month 6))
- Geometric Mean Count of Peripheral Blood Mononuclear Cells Secreting Interferon-Gamma(Month 7 (1 month after vaccination 3 at Month 6))
- Geometric Mean Titer of HCMV-specific Neutralizing Antibody After Vaccinations 1 and 2(Month 1 and 2 (one month after vaccination 1 [Day 1] and vaccination 2 [Month 1]))