A Phase 2/3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus (RSV), in Adults ≥60 Years of Age
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36,814
- 试验地点
- 535
- 主要终点
- Part A: Number of Participants With Any Solicited Adverse Reactions (ARs) (Solicited Local and/or Systemic ARs)
研究概览
简要总结
The main purpose of Part A of this study is to evaluate the safety and tolerability of mRNA-1345 vaccine and to demonstrate the efficacy of a single dose of mRNA-1345 vaccine in the prevention of a first episode of RSV-associated lower respiratory tract disease (RSV-LRTD) as compared with placebo from 14 days postinjection through 12 months.
The main purpose of Part B of this study is to evaluate the safety, tolerability and immunogenicity of a booster dose (BD) of mRNA-1345 administered 24 months after the primary dose.
详细描述
The study will be conducted in 2 phases: Phase 2 and Phase 3. In the Part A Phase 2 segment, up to 2,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio.
In the Part A Phase 3 segment, approximately 35,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio.
In the Part B substudy, 1500 participants who received a dose of mRNA-1345 in Part A Phase 3 will be randomly assigned in a 2:1 randomization ratio to receive a single BD injection of either mRNA-1345 at the selected dose or 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults ≥ 60 years of age who are primarily responsible for self-care and activities of daily living. Participants may have one or more chronic medical diagnoses (including chronic heart failure [CHF] and chronic obstructive pulmonary disease [COPD]), but should be medically stable
- •Body mass index from ≥18 kilograms (kg)/square meter (m^2) to ≤35 kg/m^2
- •Key Inclusion Criteria (Part B):
- •Randomized to and were subsequently vaccinated with the mRNA-1345 study injection in Part A at least 21 months prior to Screening.
排除标准
- •Participation in another clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of the Day 1 study injection.
- •Current participation in research involving receipt of any investigational RSV product
- •History of a serious reaction to any prior vaccination or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization.
- •Received or plans to receive any non-study vaccine within 28 days before or after the Day 1 study injection.
- •Key Exclusion Criteria (Part B):
- •Participation in another clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of BD study injection (BD Day 1).
- •History of a serious reaction to any prior vaccination, or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization.
- •Received or plans to receive any non-study vaccine (including authorized or approved vaccines for the prevention of coronavirus disease 2019 (COVID-19) regardless of type of vaccine) within 14 days before or after the BD Day 1 study injection.
- •Received or plans to receive any commercial RSV vaccination at any time prior to BD study injection (BD Day 1) or during the substudy.
- •Other inclusion and/or exclusion criteria may apply.
研究组 & 干预措施
Placebo
Single injection of mRNA-1345 matching-placebo on Day 1.
干预措施: Placebo (Drug)
mRNA-1345
Single injection of mRNA-1345 on Day 1.
干预措施: mRNA-1345 (Drug)
mRNA-1345 BD
Single injection of mRNA-1345 on BD Day 1.
干预措施: mRNA-1345 (Drug)
结局指标
主要结局
Part A: Number of Participants With Any Solicited Adverse Reactions (ARs) (Solicited Local and/or Systemic ARs)
时间窗: Up to 7 days postinjection
Solicited ARs were collected in an electronic diary (eDiary). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.
Part B: Number of Participants With Solicited Local and Systemic ARs
时间窗: Up to 7 days post-BD injection
Solicited ARs were recorded daily using electronic diaries (eDiaries). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Part A: Number of Participants With Unsolicited Adverse Events (AEs)
时间窗: Up to 28 days postinjection
An unsolicited AE was defined as any AE reported by the participant that was not specified as a solicited AR in the protocol. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Part B: Number of Participants With Unsolicited AEs
时间窗: Up to 28 days post-BD injection
An unsolicited AE was defined as any AE reported by the participant that was not specified as a solicited AR in the protocol. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Part A: Number of Participants With Medically Attended AEs (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Study Discontinuation
时间窗: Up to 24 months postinjection
MAAEs were AEs that led to an unscheduled visit to a healthcare provider. AESIs were AEs (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 was required. SAEs were AEs that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly or birth defect, or was a medically important event. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Part B: Number of Participants With MAAEs, AESIs, SAEs, and AEs Leading to Study Discontinuation
时间窗: Up to BD Day 181
MAAEs were AEs that led to an unscheduled visit to a healthcare provider. AESIs were AEs (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 was required. SAEs were AEs that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly or birth defect, or was a medically important event. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Part A: Number of Participants With Respiratory Syncytial Virus- Associated Lower RSV-LRTD With 2 or More Symptoms From 14 Days Postinjection up to 12 Months Postinjection
时间窗: From 14 days postinjection up to 12 months postinjection
RSV-LRTD: Reverse transcriptase polymerase chain reaction (RT PCR) confirmed RSV infection PLUS new or worsening of ≥2 of the following symptoms: shortness of breath, cough and/or fever (≥37.8 degrees Celsius \[°C\]), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥ 2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours.
Part A: Number of Participants With RSV-LRTD With 3 or More Symptoms From 14 Days Postinjection up to 12 Months Postinjection
时间窗: From 14 days postinjection up to 12 months postinjection
RSV-LRTD: RT PCR confirmed RSV infection PLUS new or worsening of ≥3 of the following symptoms: shortness of breath, cough and/or fever (≥37.8°C), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥ 2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours.
Part B: Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) and Respiratory Syncytial Virus Subtype B (RSV-B) Neutralizing Antibodies (nAb) at BD Day 29 Compared to Primary Dose Day 29
时间窗: Primary Dose Day 29 and BD Day 29
Antibody values reported as below lower limit of quantification (LLOQ) replaced by 0.5 \* LLOQ. Values greater than upper limit of quantification (ULOQ) replaced by ULOQ. LLOQ = 13 international units (IU)/milliliter (mL), ULOQ = 259061 IU/mL for RSV-A nAb. LLOQ = 10, ULOQ = 112476 for RSV-B nAb. Part B Per-protocol (PP) Set: all Part B randomized participants who received both Parts A and B assigned study intervention doses, had RSV immunogenicity titer results at pre-Primary Dose (baseline), had RSV immunogenicity titer results at Primary Dose Day 29, had at least 1 valid result at Revaccination Day 29, and had no major protocol deviations affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. Participants were analyzed according to the study intervention group to which they were randomized.
Number of Participants with Unsolicited Adverse Events (AEs)
时间窗: Up to 28 days after each injection
Vaccine Efficacy (VE) of mRNA-1345 to Prevent a First Episode of RSV-LRTD with 2 or More Symptoms
时间窗: From 14 days postinjection up to 12 months postinjection
VE of mRNA-1345 to prevent reverse transcription polymerase chain reaction (RT-PCR) confirmed protocol-defined RSV-LRTD, defined as 100\*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo).
Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) and Respiratory Syncytial Virus Subtype B (RSV-B) Neutralizing Antibodies
时间窗: BD Day 29
Number of Participants With Medically Attended AEs (MAAEs), Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Withdrawal
时间窗: Up to BD Day 181
VE of mRNA-1345 to Prevent a First Episode of RSV-LRTD with 3 or More Symptoms
时间窗: From 14 days postinjection up to 12 months postinjection
VE of mRNA-1345 to prevent reverse transcription polymerase chain reaction (RT-PCR) confirmed protocol-defined RSV-LRTD, defined as 100\*(1-HR ratio), where HR is the hazard ratio (mRNA-1345 versus placebo).
Geometric Mean Ratio (GMR) of Serum RSV-A and RSV-B Neutralizing Antibodies After BD Compared to After Initial Dose
时间窗: BD Day 29
Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)
时间窗: Up to 7 days after each injection
次要结局
- Part A: Number of Participants With RSV-LRTD With 2 or More Symptoms From 14 Days Postinjection up to 24 Months Postinjection(From 14 days postinjection up to 24 months postinjection)
- Part A: Number of Participants With RSV-Associated Acute Respiratory Disease (RSV-ARD) From 14 Days Postinjection up to 12 Months Postinjection(From 14 days postinjection up to 12 months postinjection)
- Part A: Number of Participants With Hospitalization Associated With Protocol-defined RSV-ARD or RSV-LRTD From 14 Days Postinjection up to 12 Months Postinjection(From 14 days postinjection up to 12 months postinjection)
- Part A: Number of Participants With All-Cause Hospitalizations From 14 Days Postinjection up to 12 Months Postinjection(From 14 days postinjection up to 12 months postinjection)
- Part A: Number of Participants With All-Cause LRTD From 14 Days Postinjection up to 12 Months Postinjection(From 14 days postinjection up to 12 months postinjection)
- Part A: Number of Participants With RSV-LRTD With 3 or More Symptoms From 14 Days Postinjection up to 24 Months Postinjection(From 14 days postinjection up to 24 months postinjection)
- Part A: Number of Participants With RSV-LRTD With 2 or More Symptoms by RSV Subtype A and RSV Subtype B From 14 Days Postinjection up to 12 Months Postinjection(From 14 days postinjection up to 12 months postinjection)
- Part A: Number of Participants With RSV-LRTD With 3 or More Symptoms by RSV Subtype A and RSV Subtype B From 14 Days Postinjection up to 12 Months Postinjection(From 14 days postinjection up to 12 months postinjection)
- Part A: Number of Participants With First Hospitalization Associated With Protocol-defined RSV-ARD or RSV-LRTD From 14 Days Postinjection up to 24 Months Postinjection(From 14 days postinjection up to 24 months postinjection)
- Part A: Change in Total Frailty Score From Baseline to 12 Months and 24 Months Postinjection, Using the Edmonton Frail Scale (EFS)(Baseline, 12 months and 24 months postinjection)
- Part A: GMT of Serum RSV nAb(Baseline (Day 1), Days 29, 181, 365, and 730)
- Part A: Geometric Mean Concentration (GMC) of Serum RSV Binding Antibodies(Baseline (Day 1), Days 29, 181, 365, and 730)
- Part A: Percentage of Participants With Seroresponse in RSV nAb(Days 29, 181, 365, and 730)
- Part A: Geometric Mean Fold-Rise (GMFR) of Postbaseline/Baseline Antibody Titers(Days 29, 181, 365, and 730)
- Part A: Percentage of Participants With ≥2-fold Increases in Antibody Titers From Baseline(Days 29, 181, 365, and 730)
- Part B: Percentage of Participants With Seroresponse of Serum RSV-A and RSV-B nAb at BD Day 29 Compared to Primary Dose Day 29(Primary Dose Day 29 and BD Day 29)
- Part B: GMT of Serum RSV-A and RSV-B nAb at BD Day 1 and BD Day 181(BD Day 1 and BD Day 181)
- Part B: GMFR of Serum RSV-A and RSV-B NAb From Pre-primary Dose (Baseline)(BD Day 1, BD Day 29, and BD Day 181)
- Part B: Percentage of Participants With Seroresponse of Serum RSV-A and RSV-B Neutralizing Antibodies From Pre-primary Dose (Baseline)(BD Day 1, BD Day 29, and BD Day 181)
- Seroresponse Rate in RSV Neutralizing Antibodies(Baseline through up to 24 months postinjection)
- GMT of Serum RSV Neutralizing Antibodies(Baseline through up to 24 months postinjection)
- Geometric Mean Concentration (GMC) of Serum RSV Binding Antibodies(Baseline through up to 24 months postinjection)
- GMFR of Serum RSV-A and RSV-B Neutralizing Antibodies from Pre-primary Dose (Baseline)(Baseline, BD Day 1, Day 29 and Day 181)
- VE of mRNA-1345 to Prevent First Hospitalization Associated with RSV-ARD or RSV-LRTD(From 14 days postinjection up to 12 months postinjection)
- Proportion of Participants with ≥4-fold Increases in Antibody Titers from Baseline(Baseline through up to 24 months postinjection)
- Seroresponse Rate (SRR) Difference Between Serum RSV-A and RSV-B Neutralizing Antibodies After BD Compared to After Initial Dose(BD Day 29)
- GMT of Serum RSV-A and RSV-B Neutralizing Antibodies(BD Day 1 and Day 181)
- VE of mRNA-1345 to Prevent a First Episode of RSV-Associated Acute Respiratory Disease (RSV-ARD)(From 14 days postinjection up to 12 months postinjection)
- Geometric Mean Fold-Rise (GMFR) of Postbaseline/Baseline Antibody Titers(Baseline through up to 24 months postinjection)
- SRR of Serum RSV-A and RSV-B Neutralizing Antibodies from Pre-primary Dose (Baseline)(Baseline, BD Day 1, Day 29 and Day 181)