A Phase I/II Study to Investigate the Safety and Immunogenicity of Quadrivalent Influenza mRNA Vaccines MRT5421, MRT5424, and MRT5429 in Healthy Participants Aged 18 Years and Above
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 908
- 试验地点
- 33
- 主要终点
- HAI Ab titer ≥ 40 (1/dil)
研究概览
简要总结
The purpose of this study was to evaluate the safety and immunogenicity of a single intramuscular (IM) injection of different formulations of Quadrivalent Influenza Vaccine (QIV) messenger ribonucleic acid (mRNA) (MRT5421, MRT5424, and MRT5429) compared to an active control (QIV- standard dose (SD), QIV- high dose (HD) [adults ≥ 65 years of age only], or quadrivalent recombinant influenza vaccine (RIV4)) in adults 18 years of age and older.
详细描述
Study duration per participant was approximately 12 months.
- Treatment duration: 1 injection of one of the 7 QIV mRNA or one of the controls
- Dose escalation with sequential enrollment
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)
盲法说明
Modified double-blind (Participants; Sites except for those preparing/administering study intervention; Sponsor's except Sponsor unblinded internal safety review committee)
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
- •Aged from 18 years on the day of inclusion or aged from 21 years on the days of inclusion, depending on the countries.
- •A female participant was eligible to participate if she was not pregnant or breastfeeding and one of the following conditions applied:
- •Was of non-childbearing potential. To be considered of non-childbearing potential, a female must of been postmenopausal for at least 1 year, or surgically sterile OR
- •Was of childbearing potential and agreed to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration.
- •A female participant of childbearing potential must of had a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before the 1st dose of study intervention
排除标准
- •Participants were excluded from the study if any of the following criteria applied:
- •Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- •Known systemic hypersensitivity to any of the study intervention components (eg, polyethylene glycol, polysorbate); history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances; any allergic reaction (eg, anaphylaxis) after administration of mRNA vaccine
- •Previous history of myocarditis, pericarditis, and / or myopericarditis
- •Known history of previous episodes of Gillian-Barre Syndrome (GBS), neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis
- •Participants with an ECG that is consistent with possible myocarditis or pericarditis or, in the opinion of the investigator, demonstrates clinically relevant abnormalities that may affect participant safety or study results
- •Self-reported thrombocytopenia, contraindicating Intramuscular vaccination based on Investigator's judgment
- •Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating Intramuscular vaccination based on Investigator's judgment
- •Chronic illness that, in the opinion of the Investigator, was at a stage where it might have interfered with study conduct or completion
- •Moderate or severe acute illness / infection (according to Investigator's judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of vaccination. A prospective participant was not included in the study until the condition was resolved or the febrile event subsided
- •Participant who had acute infection symptoms or a positive SARS-CoV-2 RT-PCR or antigen test in the past 10 days prior to the 1st visit (V01)
- •Receipt of any vaccine in the 4 weeks preceding study intervention administration or planned receipt of any vaccine in the 4 weeks following study intervention administration
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months
- •Previous vaccination against influenza in the previous 6 months with an investigational or marketed vaccine
- •Receipt of any mRNA vaccine/product in the 2 months preceding study intervention administration
- •NOTE: The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 3
participants received a single dose of QIV mRNA vaccine MRT5429
干预措施: Quadrivalent Influenza mRNA Vaccine MRT5429 (Biological)
Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 2
participants received a single dose of QIV mRNA vaccine MRT5424
干预措施: Quadrivalent Influenza mRNA Vaccine MRT5424 (Biological)
Quadrivalent Influenza RIV4 Vaccine
participants received a single dose of RIV4 vaccine
干预措施: Quadrivalent Recombinant Influenza Vaccine (Biological)
Quadrivalent Influenza mRNA Vaccine MRT5424 Dose 1
participants received a single dose of QIV mRNA vaccine MRT5424
干预措施: Quadrivalent Influenza mRNA Vaccine MRT5424 (Biological)
Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 2
participants received a single dose of QIV mRNA vaccine MRT5429
干预措施: Quadrivalent Influenza mRNA Vaccine MRT5429 (Biological)
Quadrivalent Influenza SD Vaccine
participants received a single dose of QIV-SD vaccine
干预措施: Quadrivalent Influenza Standard Dose Vaccine (Biological)
Quadrivalent Influenza HD Vaccine
participants received a single dose of QIV -HD vaccine (for adults ≥ 65 years of age only)
干预措施: Quadrivalent Influenza High-Dose Vaccine (Biological)
Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 4
participants received a single dose of QIV mRNA vaccine MRT5429
干预措施: Quadrivalent Influenza mRNA Vaccine MRT5429 (Biological)
Quadrivalent Influenza mRNA Vaccine MRT5429 Dose 1
participants received a single dose of QIV mRNA vaccine MRT5429
干预措施: Quadrivalent Influenza mRNA Vaccine MRT5429 (Biological)
Quadrivalent Influenza mRNA Vaccine MRT5421 Dose 1
participants received a single dose of QIV mRNA vaccine MRT5421
干预措施: Quadrivalent Influenza mRNA Vaccine MRT5421 (Biological)
结局指标
主要结局
HAI Ab titer ≥ 40 (1/dil)
时间窗: Day 29
HAI Ab titer ≥ 40 (1/dil) at D29
Number of participants with immediate unsolicited systemic adverse events (AEs)
时间窗: Within 30 minutes after injection
Unsolicited systemic AEs that occur within 30 minutes after vaccination
Number of participants with solicited injection site reactions
时间窗: Up to 7 days after injection
Adverse reactions pre-listed in the protocol and case report form (CRF) Injection site reactions: Injection site pain, Injection site erythema, and Injection site swelling
Number of participants with solicited systemic reactions
时间窗: Up to 7 days after injection
Adverse reactions pre-listed in the protocol and case report form (CRF) Systemic reactions: fever, headache, fatigue, myalgia, arthralgia, chills
Number of participants with unsolicited AEs
时间窗: Up to 28 days after injection
AEs that do not fulfill the conditions of solicited reactions
Number of participants with medically attended adverse events (MAAEs)
时间窗: Up to 180 days after injection
MAAEs reported up to 180 days after injection
Number of participants with serious adverse events (SAEs)
时间窗: Throughout the study (approximately 12 months)
SAEs reported throughout the study
AESIs reported throughout the study
时间窗: AESIs reported throughout the study (approximatley 12 months)
AESIs reported throughout the study (approximately 12 months)
Number of participants with adverse events of special interests (AESIs)
时间窗: Throughout the study (approximately 12 months)
AESIs reported throughout the study
Number of participants with out-of-range biological test results
时间窗: Up to 8 days after injection
Out-of-range biological test results (including shift from baseline values)
Geometric Mean Titer (GMT)
时间窗: At Day 1 and Day 29
Hemagglutinin inhibition (HAI) antibody (Ab) titers at D01 and D29
Geometric Mean of individual Titer Ratio (GMTR)
时间窗: At Day 1 and Day 29
Individual HAI Ab titer ratio D29/D01
Seroconversion
时间窗: At Day 1 and Day 29
Number of participants with HAI Ab titer \< 10 \[1/dil\] at Day 1 and post-vaccination titer ≥ 40 \[1/dil\] at Day 29, or titer ≥ 10 \[1/dil\] at Day 1 and a ≥ 4-fold-rise in titer \[1/dil\] at Day 29
Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs) After Vaccine Administration
时间窗: Within 30 minutes after vaccine administration on Day 1
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions, that is, pre-listed in the case report form in terms of diagnosis and onset window post-vaccination. Systemic AEs are all AEs that were not injection or administration site reactions. Immediate events are recorded to capture medically relevant unsolicited systemic AEs which occur within the first 30 minutes after vaccination.
Number of Participants With Solicited Injection Site Reactions After Vaccine Administration
时间窗: Within 7 days after vaccine administration on Day 1
An adverse reaction (AR) is any noxious and unintended response to a study vaccine related to any dose. Solicited injection site reactions are reactions at and around the injection site of the vaccine observed and reported under the conditions (nature and onset) pre-listed in the protocol and case report form.
Number of Participants With Solicited Systemic Reactions After Vaccine Administration
时间窗: Within 7 days after vaccine administration on Day 1
An AR is any noxious and unintended response to a study vaccine related to any dose. Solicited systemic reactions are systemic AEs observed and reported under the conditions (nature and onset) pre-listed in the protocol and case report form.
Number of Participants With Unsolicited Adverse Events After Vaccine Administration
时间窗: Within 28 days after vaccine administration on Day 1
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE is an observed AE that does not fulfill the conditions of solicited reactions, that is, pre-listed in the case report form in terms of diagnosis and onset window post-vaccination.
Number of Participants With Medically Attended Adverse Events (MAAEs)
时间窗: Within 180 days after vaccine administration on Day 1
An MAAE is a new onset or a worsening of a condition that prompts the participant or participant's parent/legally acceptable representative to seek unplanned medical advice at a physician's office or emergency department.
Number of Participants With Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs)
时间窗: From the vaccine administration (Day 1) until 12 months after vaccine administration, approximately 366 days
An SAE is any untoward medical occurrence that at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event. An AESI (serious or non-serious) is 1 of scientific and medical concern specific to the Sponsor's study vaccine or program, for which ongoing monitoring and rapid communication by the investigator to the Sponsor can be appropriate. The AESIs was defined as anaphylactic reactions (including bronchospasms, and laryngeal spasms), Guillain-Barré syndrome, neuritis (including Bell's palsy), myocarditis, pericarditis, myopericarditis and vasculitis.
Number of Participants With Abnormal Biological Test Results
时间窗: Within 8 days after vaccine administration on Day 1
Blood samples were collected for the assessment of abnormal hematology and clinical chemistry parameters. Only participants with outside the normal range hematology and clinical chemistry parameters are reported.
Geometric Mean of Hemagglutination Inhibition (HAI) Antibody (Ab) Titer at Day 1
时间窗: Day 1
The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% confidence interval (CI) was based on the Clopper-Pearson method.
Geometric Mean of Hemagglutination Inhibition Antibody Titer at Day 29
时间窗: Day 29
The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI was based on the Clopper-Pearson method.
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 1
时间窗: Day 1
The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Detectable Hemagglutination Inhibition Antibody Titer >=1:10 at Day 29
时间窗: Day 29
The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Geometric Mean Ratio of Hemagglutination Inhibition Antibody Titer at Day 29
时间窗: Days 1 and 29
The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The geometric mean ratio of antibody titer at post-vaccination over pre-vaccination is reported. The 95% CI was based on the Clopper-Pearson method.
Percentage of Participants With Seroconversion of Hemagglutination Inhibition Antibody Titer at Day 29
时间窗: Day 29
The seroconversion was defined as titer \<10 on Day 1 and post-injection titer \>=40 on Day 29; or defined as titer \>=10 on Day 1 and a \>=4-fold increase in titer on Day 29. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With Hemagglutination Inhibition Antibody Titer >=1:40 at Day 29
时间窗: Day 29
The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
Percentage of Participants With >=2 and >=4 Fold Increase in Hemagglutination Inhibition Antibody Titer at Day 29
时间窗: Days 1 and 29
The HAI Ab was measured by hemagglutinin inhibition using quality control sera (sheep, ferret and/or human sera) measurement method. The 95% CI for the single percentage was based on the Clopper-Pearson method. The percentages are rounded off to the tenth decimal place.
次要结局
- Neutralizing Ab titers at D01 and D29(At Day 1 and Day 29)
- Individual neutralizing antibodies titer ratio(At Day 1 and Day 29)
- 2-fold and 4-fold increase in neutralizing titers(Day 1 through Day 29)
- Geometric Mean of Neutralization Test (NT) Antibody Titer at Days 1 and 29(Days 1 and 29)
- Geometric Mean Ratio of Neutralization Test Antibody Titer at Day 29(Days 1 and 29)
- Percentage of Participants With >=2 and >=4 Fold Increase in Neutralization Test Antibody Titer at Day 29(Days 1 and 29)