A Phase 2 Randomized, Observer-Blind, Placebo-Controlled Study to Assess the Safety, Reactogenicity, and Immunogenicity of the SARS CoV-2 Vaccine ARCT-021 in Healthy Adult Participants
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 581
- 试验地点
- 15
- 主要终点
- Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Each Priming Vaccination
研究概览
简要总结
This is a Phase 2, randomized, placebo-controlled, and observer-blind study in healthy adults.
The study will evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 RNA vaccine candidate against COVID-19:
As 2 doses (at two different dose levels), separated by 28 days or as 1 dose
In adults 18 years of age and older
详细描述
This is a multiregional, multicenter, Phase 2, randomized, observer-blind study designed to evaluate the safety, reactogenicity, and immunogenicity of the study vaccine in younger and older adult participants. Enrolled participants will be randomly assigned to receive either study vaccine ARCT-021 or placebo (sterile saline).
Approximately 600 participants (300 each in younger [18 to <56 years of age in United States or 21 to <56 years of age in Singapore] and older [≥56 years of age] participants) will be enrolled (including at least 50% of participants in the older cohort ≥65 years of age). Participants will be stratified by age and then randomly assigned (3 ARCT-021:1 placebo) to receive 2 doses of study vaccine separated by 28 days. At 180 days after second study vaccination (Day 208), participants in Study Groups 1, 2, and 3 will be randomly assigned again to receive a single booster dose of study vaccine (randomly assigned as 1 ARCT-021:1 placebo). Study Group 4 will not be randomized but will receive 1 dose of placebo at Day 208. Study Groups are summarized in Table 1. Study vaccine will be administered in an observer-blind fashion. Participants will be followed for safety and immunogenicity through 180 days after booster vaccination (Day 388). At a subset of clinical sites, all enrolled participants will also undergo blood sampling for evaluation of CMI responses.
Vaccine doses will be assigned as follows:
Younger Age Cohort:
Study Group 1: n= 75 participants, ARCT-021 7.5 µg (first dose), Placebo (second dose Study Group 2: n= 75 participants, ARCT-021 5.0 µg (first dose), 5.0 µg (second dose) Study Group 3: n= 75 participants, ARCT-021 7.5 µg (first dose), 7.5 µg (second dose) Study Group 4: n= 75 participants, Placebo (first dose), Placebo (second dose)
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)
盲法说明
Observer blind
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
- •Individuals who:
- •are able to provide consent
- •agree to comply with all study visits and procedures
- •are willing and able to adhere to study restrictions
- •are sexually active and willing to adhere to contraceptive requirements
- •are male or female ≥18 or (in Singapore) ≥21 years of age
- •are medically stable
排除标准
- •Individuals who:
- •have had SARS-CoV-2 infection or COVID-19 disease.
- •have had cancer except for cancers that were treated and that have low risk of returning
- •have chronic kidney disease
- •have some chronic lung diseases
- •have some heart conditions
- •have compromised immune systems
- •have sickle cell disease or some other blood disorders
- •are current smokers and/or use illegal drugs
- •have Type 2 diabetics
- •are immunocompromised, immunodeficient or have had a transplant
- •have autoimmune disease
- •have other severe or uncontrolled diseases or disease that may interfere with the interpretation of the study
- •have a positive test for hepatitis B or C or human immunodeficiency virus
- •have had a severe reaction to previous investigational vaccines
- •have a fever or are feeling sick close to the time of the first vaccination of the study
- •have positive drug test at screening
- •are pregnant
- •are breastfeeding
- •have a bleeding disorder
- •have previously received an investigational coronavirus vaccine (SARS-CoV(1) or MERS) or who plan to be in other COVID-19 studies
- •have recently been vaccinated with other vaccines
- •have recently received blood products
- •who work at one of the clinic sites participating in this study, work at Arcturus, who work at other companies that monitor the study or close family members to the sites, Arcturus, or partners involved in study monitoring
- •other restrictions may apply
研究组 & 干预措施
Study Group 1, Younger Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, one dose of Placebo (saline) on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: ARCT-021 single dose priming (Biological)
Study Group 1, Younger Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, one dose of Placebo (saline) on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: Randomized booster (Biological)
Study Group 2, Younger Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: ARCT-021 two lower dose priming (Biological)
Study Group 2, Younger Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: Randomized booster (Biological)
Study Group 3, Younger Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: ARCT-021 two higher dose priming (Biological)
Study Group 3, Younger Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: Randomized booster (Biological)
Study Group 4, Younger Adult Participants
Participants will receive one of Placebo (Saline) on Day 0, one dose of Placebo on Day 28, and one dose of Placebo on Day 208
干预措施: Placebo (two doses), priming (Biological)
Study Group 4, Younger Adult Participants
Participants will receive one of Placebo (Saline) on Day 0, one dose of Placebo on Day 28, and one dose of Placebo on Day 208
干预措施: Placebo booster (Biological)
Study Group 1, Older Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, one dose of Placebo (saline) on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: ARCT-021 single dose priming (Biological)
Study Group 1, Older Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, one dose of Placebo (saline) on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: Randomized booster (Biological)
Study Group 2, Older Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: ARCT-021 two lower dose priming (Biological)
Study Group 2, Older Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: Randomized booster (Biological)
Study Group 3, Older Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: ARCT-021 two higher dose priming (Biological)
Study Group 3, Older Adult Participants
Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo
干预措施: Randomized booster (Biological)
Study Group 4, Older Adult Participants
Participants will receive one dose of Placebo (saline) on Day 0, a second dose of Placebo on Day 28 and a third dose of Placebo on Day 208
干预措施: Placebo (two doses), priming (Biological)
Study Group 4, Older Adult Participants
Participants will receive one dose of Placebo (saline) on Day 0, a second dose of Placebo on Day 28 and a third dose of Placebo on Day 208
干预措施: Placebo booster (Biological)
结局指标
主要结局
Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Each Priming Vaccination
时间窗: For 7 days following each dose administration (Day 0 up to Day 7 for Vaccination 1 and Day 29 up to Day 35 for Vaccination 2)
Per prespecified analysis, solicited local adverse events were defined as pain, erythema, swelling, or injection site tenderness. Solicited adverse reactions were recorded by the participant in an eDiary. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Booster Vaccination
时间窗: For 7 days following each dose administration (Day 208 up to Day 215)
Per prespecified analysis, solicited local adverse events were defined as pain, erythema, swelling, or injection site tenderness. Solicited adverse reactions were recorded by the participant in an eDiary. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Each Priming Vaccination
时间窗: For 7 days following each dose administration (Day 0 up to Day 7 for Vaccination 1 and Day 29 up to Day 35 for Vaccination 2)
Per prespecified analysis, solicited systemic adverse events were defined as fever, headache, fatigue, myalgia, arthralgia, nausea, chills, diarrhea, dizziness, and vomiting. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Booster Vaccination
时间窗: For 7 days post booster dose administration (Day 208 up to Day 215)
Per prespecified analysis, solicited systemic adverse events were defined as fever, headache, fatigue, myalgia, arthralgia, nausea, chills, diarrhea, dizziness, and vomiting. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Each Priming Vaccination
时间窗: 28 days following each dose administration (Day 0 up to Day 28 for Vaccination 1 and Day 29 up to Day 56 for Vaccination 2)
An unsolicited AE was defined as any AE (serious and nonserious) occurring after administration of first dose of study vaccine and before the end of study. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Booster Vaccination
时间窗: 28 days following each dose administration (Day 208 up to 236 days)
An unsolicited AE was defined as any AE (serious and nonserious) occurring after administration of first dose of study vaccine and before the end of study. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Treatment-Emergent Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE) and New Onset of Chronic Disease (NOCD) Post Each Priming Vaccination
时间窗: Up to Day 207
SAEs were defined as any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, resulted in a congenital anomaly or birth defect, or was an important medical event. An NOCD was defined as any AE that led to the new diagnosis of a chronic medical condition that was not present or suspected prior to enrollment. An MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) to a healthcare practitioner. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Treatment-emergent Serious Adverse Events, Medically Attended Adverse Events and New Onset of Chronic Disease Post Booster Vaccination
时间窗: Day 208 to early termination (up to 396 days)
SAEs were defined as any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, resulted in a congenital anomaly or birth defect, or was an important medical event. An NOCD was defined as an AE that led to the new diagnosis of a chronic medical condition that was not present or suspected prior to enrollment. An MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) to a healthcare practitioner. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Geometric Mean Titer (GMT) of Serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies Post Priming Vaccination
时间窗: Day 1
GMT of SARS-CoV-2 Neutralizing Antibodies Post Priming Vaccination
时间窗: Day 56
GMT of SARS-CoV-2 Neutralizing Antibodies Post Booster Vaccination
时间窗: Day 236
Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Neutralizing Antibody Titers Post Priming Vaccination
时间窗: Day 56
GMFR is reported as a ratio to baseline (Day 0).
Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Neutralizing Antibody Titers Post Booster Vaccination
时间窗: Day 208
GMFR is reported as a ratio to baseline (Day 0).
Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 208
时间窗: Baseline up to Day 208
GMFR in SARS-CoV-2 Neutralizing Antibody Titers Post Booster Vaccination
时间窗: Day 236
GMFR is reported as a ratio to baseline (Day 0).
Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 56
时间窗: Baseline up to Day 56
Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 236
时间窗: Baseline up to Day 236
次要结局
- Percentage of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels(Day 56)
- Geometric Mean Concentration of SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Post Priming Vaccination(Days 0 and 56)
- Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Before Vaccination to Day 56(Day 56)
- Geometric Mean Concentration of SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Post Booster Vaccination(Day 208 and 236)