A Phase 2, Randomized, Observer-Blind, Placebo-Controlled, Dose Confirmation Study to Evaluate the Safety, Tolerability, and Immunogenicity of Zika Vaccine mRNA-1893 in Adults Aged 18 Through 65 Years and Living in Endemic and Non-Endemic Flavivirus Areas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 808
- 试验地点
- 9
- 主要终点
- Number of Participants With Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
研究概览
简要总结
This clinical study will evaluate the safety, tolerability, and reactogenicity of 2 dose levels of messenger RNA (mRNA)-1893 Zika vaccine in comparison to a placebo control in healthy participants who are flavivirus-seronegative and in participants who are flavivirus-seropositive.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Understands and agrees to comply with the study procedures and provides written informed consent.
- •According to investigator assessment, is in good general health and can comply with study procedures.
- •Female participants of childbearing potential may be enrolled in the study if the participant: has a negative pregnancy test at the Eligibility Visit and on the day of the first investigational product (IP) injection; has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first IP injection; has agreed to continue adequate contraception through 3 months following the last IP injection; and is not currently breastfeeding.
排除标准
- •Participant is acutely ill or febrile (temperature ≥38.0°Celsius/100.4°Farenheight) on the day of the first or second vaccination.
- •Participant had prior administration of a ZIKV vaccine candidate during a clinical study investigation.
- •Participant had prior administration of a marketed dengue vaccine or dengue vaccine candidate under clinical study investigation.
- •Participant has a body mass index (BMI) from ≤18 or ≥35 kilograms (kg)/square meter (m^2).
- •Participant has a history of myocarditis, pericarditis, or myopericarditis.
- •Participant has a history of a diagnosis or condition that, in the judgement of the investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. "Clinically unstable" is defined as a diagnosis or condition requiring significant changes in management or medication within the 2 months prior to screening and includes ongoing work-up of an undiagnosed illness that could lead to a new diagnosis or condition.
- •Participant has any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that in the opinion of the investigator, might pose a risk due to participation in the study or could interfere with the interpretation of study results.
- •Participant has as a history of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine, including an mRNA vaccine or any components of an mRNA vaccine.
- •Participant has received or plans to receive a nonstudy vaccine (including authorized or approved vaccines for the prevention of COVID-19) ≤28 days prior to the first IP injection or within 28 days prior to or after any IP injection. Licensed influenza vaccine received within 14 days prior to the first IP injection or plans to receive a licensed influenza vaccine 14 days prior to through 14 days following each IP injection are not exclusionary.
- •Participant has received systemic immunoglobulins or blood products within 3 months prior to the day of enrollment.
- •Participant has donated ≥450 milliliters (mL) of blood products within 28 days of the Day 1 Visit.
- •Participant has participated in an interventional clinical study within 28 days prior to the day of enrollment or plans to do so while enrolled in this study.
研究组 & 干预措施
mRNA-1893 Low Dose (2-Dose Regimen)
Participants will receive mRNA-1893 at a low dose level administered as a 2-dose regimen with 28-day (-3/+7 days) interval between vaccinations (administered on Day 1 and Day 29).
干预措施: mRNA-1893 (Biological)
mRNA-1893 High Dose (2-Dose Regimen)
Participants will receive mRNA-1893 at a high dose level administered as a 2-dose regimen with 28-day (-3/+7 days) interval between vaccinations (administered on Day 1 and Day 29).
干预措施: mRNA-1893 (Biological)
mRNA-1893 High Dose (1-Dose Regimen)
Participants will receive placebo matching to mRNA-1893 on Day 1 and mRNA-1893 at a high dose level administered as a 1-dose regimen (administered on Day 29). There will be 28-day (-3/+7 days) interval between vaccinations.
干预措施: mRNA-1893 (Biological)
mRNA-1893 High Dose (1-Dose Regimen)
Participants will receive placebo matching to mRNA-1893 on Day 1 and mRNA-1893 at a high dose level administered as a 1-dose regimen (administered on Day 29). There will be 28-day (-3/+7 days) interval between vaccinations.
干预措施: Placebo (Biological)
Placebo
Participants will receive placebo matching to mRNA-1893 administered as a 2-dose regimen with 28-day (-3/+7 days) interval between vaccinations (administered on Day 1 and Day 29).
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Participants With Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
时间窗: Up to 7 days post-vaccination
Solicited ARs (local and systemic) were collected in the electronic diary. Local ARs included: pain, erythema (redness), swelling/induration (hardness). Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, body temperature (potentially fever), and chills. A summary of all serious adverse events (SAEs) and all nonserious adverse events (AEs) ("Other"), regardless of causality, is in Reported "Adverse Events" section.
Geometric Mean Titer (GMT) of Zika Virus (ZIKV)-Specific Neutralizing Antibodies (nAbs) at Day 57, as Measured by 50% Plaque Reduction Neutralization Test (PRNT50)
时间窗: Day 57
Antibody values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5 \* LLOQ. Values that were greater than the upper limit of quantification (ULOQ) were converted to the ULOQ. LLOQ=91; ULOQ=24814. 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.
Number of Participants With Unsolicited Adverse Events (AEs)
时间窗: Up to 28 days post-vaccination
An unsolicited AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Unsolicited AEs were AEs that were not included in the protocol-defined solicited ARs. A treatment-emergent adverse event (TEAE) was defined as any AE not present before exposure to vaccine or any AE already present that worsened in intensity or frequency after exposure. A summary of all SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.
Percentage of Participants With Seroconversion at Day 57, as Measured by PRNT50
时间窗: Day 57
Seroconversion was defined as an increase in ZIKV-specific nAb titer from below the LLOQ to a titer equal to or above LLOQ, or an increase of at least 4-fold in ZIKV-specific nAb titer in participants with pre-existing nAb titers. LLOQ=91; ULOQ=24814.
Percentage of Participants With Seroconversion at Day 57, as Measured by PRNT80
时间窗: Day 57
Seroconversion was defined as an increase in ZIKV-specific nAb titer from below the LLOQ to a titer equal to or above LLOQ, or an increase of at least 4-fold in ZIKV-specific nAb titer in participants with pre-existing nAb titers. LLOQ=91; ULOQ=24814.
Number of Participants With Serious Adverse Events (SAEs), AEs of Special Interest (AESIs)
时间窗: Day 1 through Day 196 for Main Study and Day 197 through Day 700 for Extension Period
An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was a congenital anomaly/birth defect, or was an important medical event. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor were required. A summary of all SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.
Number of Participants With Medically Attended AEs (MAAEs)
时间窗: Day 1 through Day 196 for Main Study and Day 197 through Day 700 for Extension Period
An MAAE was an AE that led to an unscheduled visit to a healthcare practitioner. Note that the generation of the tables for the MAAE data for the Main Study occurred after the start of the Extension Period. Therefore, some of the MAAE data for this outcome measure may appear both in the Main Study and the Extension Period. A summary of all SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.
GMT of ZIKV-specific nAbs at Day 57, as Measured by 80% Plaque Reduction Neutralization Test (PRNT80)
时间窗: Day 57
Antibody values reported as below the LLOQ were replaced by 0.5 \* LLOQ. Values that were greater than the ULOQ were converted to the ULOQ. LLOQ=91; ULOQ=24814. 95% CI was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.
次要结局
- Geometric Mean Fold Rise (GMFR) of ZIKV-Specific nAbs at Days 8, 29, 36, and 57, as Measured by PRNT50 and PRNT80(Days 8, 29, 36, and 57)
- GMFR of ZIKV-Specific nAbs at Days 8, 29, 36, and 57, as Measured by MN(Days 8, 29, 36, and 57)
- Percentage of Initially Seronegative Participants With a Seroresponse at Days 8, 29, and 36, as Measured by PRNT50 and PRNT80(Days 8, 29, and 36)
- Percentage of Initially Seronegative Participants With a Seroresponse at Days 8, 29, 36, and 57, as Measured by MN(Days 8, 29, 36, and 57)
- GMT of ZIKV-Specific nAbs at Days 1, 8, 29, 36, and 57, as Measured by Microneutralization (MN)(Days 1, 8, 29, 36, and 57)
- GMT of ZIKV-Specific nAbs at Days 1, 8, 29, and 36, as Measured by PRNT50 and PRNT80(Days 1, 8, 29, and 36)
- Percentage of Participants With Seroconversion at Days 8, 29, and 36, as Measured by PRNT50 and PRNT80(Days 8, 29, and 36)
- Percentage of Participants With Seroconversion at Days 8, 29, 36, and 57, as Measured by MN(Days 8, 29, 36, and 57)
- Percentage of Initially Seropositive Participants With a 2-Fold Increase in ZIKV-Specific nAb Titers as Compared With Baseline, as Measured by PRNT50 and PRNT80(Days 8, 29, 36, and 57)
- Percentage of Initially Seropositive Participants With a 4-Fold Increase in ZIKV-Specific nAb Titers as Compared With Baseline, as Measured by PRNT50 and PRNT80(Days 8, 29, 36, and 57)
- Percentage of Initially Seropositive Participants With a 2-Fold Increase in ZIKV-Specific nAb Titers as Compared With Baseline, as Measured by MN(Days 8, 29, 36, and 57)
- Percentage of Initially Seropositive Participants With a 4-Fold Increase in ZIKV-Specific nAb Titers as Compared With Baseline, as Measured by MN(Days 8, 29, 36, and 57)