A Phase 1/2, Randomized, Observer-Blind, Controlled, Dose-Ranging Study of mRNA-1608, an HSV-2 Therapeutic Candidate Vaccine, in Healthy Adults 18 to 55 Years of Age With Recurrent HSV-2 Genital Herpes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 303
- 试验地点
- 43
- 主要终点
- Number of Participants with Unsolicited Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to generate safety and immunogenicity data and establish a proof-of-concept of clinical benefit of the mRNA-1608 vaccine candidate.
详细描述
Participants with a history of recurrent genital herpes will be randomly assigned in a 1:1:1:1 ratio to receive mRNA-1608 at 1 of the 3 dose levels or control (BEXSERO) administered as 2 doses at 0 and 2 months (Day 1 and Day 57).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant has a diagnosis of genital HSV-2 infection for at least 1 year before the Screening Visit.
- •Seropositive for HSV-2 as determined by Western Blot.
- •Participant has a history of recurrent genital herpes defined as at least 3 and no more than 9 reported genital herpes recurrences in the 12 months preceding the Screening Visit, or if currently on suppressive therapy, prior to initiation of suppressive therapy.
- •Willing to refrain from taking suppressive antiviral therapy from the Screening Visit until the end of the study.
- •Willing to refrain from the use of episodic antiviral therapy during the three 28-day anogenital swabbing periods. Episodic therapy may be used outside the three 28-day swabbing periods.
- •For female participants of childbearing potential: negative pregnancy test, adequate contraception, and not currently breastfeeding.
排除标准
- •Prior immunization with a vaccine containing HSV antigens.
- •History of any form of ocular HSV infection, HSV-related erythema multiforme, or HSV-related neurological complications.
- •History of genital HSV-1 infection.
- •History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) types 1 or 2 (HIV-1, HIV-2).
- •Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mRNA vaccine(s) or any components of the mRNA vaccines.
- •Previously received BEXSERO or other vaccine to prevent serogroup B meningococcal disease (also known as meningitis B).
- •History of allergic disease or reactions likely to be exacerbated by any component of BEXSERO vaccine.
- •Has received or plans to receive any licensed or authorized vaccine, including COVID-19 vaccines, ≤ 28 days prior to the first study injection (Day 1), or plans to receive a licensed or authorized vaccine within 28 days before or after study injection with the exception of licensed influenza vaccines, which may be received more than 14 days before or after any study injection.
- •Note: Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
mRNA-1608 Dose A
Participants will receive 2 intramuscular (IM) injections of mRNA-1608 at Dose Level A, each dose administered at 0 and 2 months (Day 1 and Day 57).
干预措施: mRNA-1608 (Biological)
mRNA-1608 Dose C
Participants will receive 2 IM injections of mRNA-1608 at Dose Level C, each dose administered at 0 and 2 months (Day 1 and Day 57).
干预措施: mRNA-1608 (Biological)
BEXSERO
Participants will receive 2 IM injections of BEXSERO, each dose administered at 0 and 2 months (Day 1 and Day 57).
干预措施: BEXSERO (Biological)
mRNA-1608 Dose B
Participants will receive 2 IM injections of mRNA-1608 at Dose Level B, each dose administered at 0 and 2 months (Day 1 and Day 57).
干预措施: mRNA-1608 (Biological)
结局指标
主要结局
Number of Participants with Unsolicited Adverse Events (AEs)
时间窗: Up to Day 85 (28 days after each injection)
Number of Participants with AEs Leading to Discontinuation From Study
时间窗: Day 1 to Day 393 (EoS)
Number of Participants with Adverse Events of Special Interest (AESIs)
时间窗: Day 1 to Day 393 (EoS)
Number of Participants with Serious Adverse Events (SAEs)
时间窗: Day 1 to Day 393 (end of study [EoS])
Number of Participants with Medically-Attended AEs (MAAEs)
时间窗: Day 1 through 6 months after last study injection (Day 225)
Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
时间窗: Up to Day 64 (7 days after each injection)
次要结局
- Number of Genital Herpes Recurrences, Counted Starting 14 Days After the Second Study Injection to 6 Months After Second Study Injection(Day 71 to Day 225)
- Change From Baseline (28 Days Prior to the First Study Injection) to 6 Months After the Second Study Injection in Genital Herpes Lesion Rate (Proportion of Days With Lesions Present)(Baseline (Day -27 to Day 1), Day 197 to Day 225)
- Change From Baseline (28 Days Prior to the First Study Injection) to 6 Months After the Second Study Injection in HSV-2 Genital Shedding Rate (Proportion of HSV-2 DNA Positive Anogenital Swabs)(Baseline (Day -27 to Day 1), Day 197 to Day 225)
- Change From Baseline (28 Days Prior to the First Study Injection) to 2 Months After the Second Study Injection in Genital Herpes Lesion Rate (Proportion of Days With Lesions Present)(Baseline (Day -27 to Day 1), Day 85 to Day 113)
- Number of Participants With Vaccine Seroresponse(Baseline (Day 1), Days 85 and 225)
- Number of Genital Herpes Recurrences, Counted Starting 14 Days After the Second Study Injection to 12 Months After Second Study Injection(Day 71 to Day 393)
- Change From Baseline (28 Days Prior to the First Study Injection) to 2 Months After the Second Study Injection in HSV-2 Genital Shedding Rate (Proportion of HSV-2 Deoxyribonucleic acid [DNA] Positive Anogenital Swabs)(Baseline (Day -27 to Day 1), Day 85 to Day 113)
- Geometric Mean Titer (GMT) of mRNA-1608 Antigen-Specific Binding Antibodies (bAbs) at 1 and 6 Months After the Second Study Injection(Days 85 and 225)
- Geometric Mean Fold Rise (GMFR) of mRNA-1608 Antigen-Specific bAbs From Baseline to 1 and 6 Months After the Second Study Injection(Baseline (Day 1), Days 85 and 225)