A Phase 3, Multicenter, Observer-blind, Randomized, Controlled Study to Evaluate the Immunogenicity, Reactogenicity, and Safety of a Self-Amplifying RNA COVID-19 Vaccine (ARCT-2303), Administered Concomitantly With Quadrivalent Influenza Vaccines, in Adults
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,514
- 试验地点
- 29
- 主要终点
- Groups 2a and 2b and ARCT-154-J01 Historical Control: Geometric Mean Titers (GMT) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibody Titers Against Omicron XBB.1.5 Subvariant at Day 29
研究概览
简要总结
This is a multicenter, observer-blind, randomized, controlled phase 3 study to evaluate the immunogenicity, reactogenicity, and safety of an investigational self-amplifying RNA COVID-19 vaccine (ARCT-2303) administered concomitantly with quadrivalent influenza vaccines or standalone in adults who previously received authorized COVID-19 vaccine.
详细描述
Approximately 1680 participants previously vaccinated with authorized COVID-19 vaccine will be enrolled in this study in two age cohorts (younger adults and older adults). Within each cohort, participants will be randomly assigned in a ratio of 1:1:1 to receive the ARCT-2303 vaccine concomitantly with a quadrivalent influenza vaccine, the ARCT-2303 vaccine and placebo, or the quadrivalent influenza vaccine and placebo. The assessment of immunogenicity will be performed 28 days after vaccination. To provide equal benefit from the participation in the study and complete seasonal vaccination against COVID-19 and influenza, a switchover vaccine dose (influenza, ARCT-2303 or placebo) will be administered 28 days after initial vaccination. All participants will be followed up for safety assessment until the end of the study.
A historical control group vaccinated on a similar schedule (ARCT-154 vaccine) from a previous study (ARCT-154-J01) will be used to compare with the immunogenicity of the ARCT-2303 vaccine.
Cohort A (younger adults; approximately 1200 participants):
- Group 1a (ARCT-2303/Influenza vaccine): participants will receive one dose of ARCT-2303 and one dose of Influenza vaccine (opposite arms) on Day 1, and one dose of placebo on Day 29.
- Group 2a (ARCT-2303): participants will receive one dose of ARCT-2303 and one dose of placebo (opposite arms) on Day 1, and one dose of Influenza vaccine on Day 29.
- Group 3a (Influenza vaccine): participants will receive one dose of Influenza vaccine and one dose of placebo (opposite arms) on Day 1, and one dose of ARCT-2303 on Day 29.
Cohort B (older adults; approximately 480 participants):
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •1, Individuals are male, female, or transgender adults ≥18 years of age.
- •2. Healthy participants or participants with pre-existing stable medical conditions.
- •3. Participant or legally authorized representatives must freely provide documented informed consent prior to study procedures being performed.
- •4. Individuals must have been previously vaccinated with COVID-19 vaccines.
- •5. Individuals of childbearing potential must be willing to adhere to contraceptive requirements.
排除标准
- •Individuals with acute medical illness or febrile illness.
- •Individuals with a positive SARS-CoV-2 rapid antigen test at Screening.
- •Individuals with a history of COVID-19 or virologically confirmed SARS-CoV-2 infection within the past 5 months or history of COVID-19 with ongoing sequelae.
- •Individuals with a known history of severe hypersensitivity reactions, including anaphylaxis, or other significant adverse reactions to any components of mRNA vaccine, or influenza vaccine, including egg protein.
- •Individuals who have a positive pregnancy test at the Screening visit or who intend to become pregnant or breastfeed during the study.
- •Individuals with a history of myocarditis, pericarditis, myopericarditis or cardiomyopathy.
- •Individuals with a history of Guillain-Barré syndrome, encephalomyelitis, or transverse myelitis.
- •Individuals with a history of congenital or acquired immunodeficiency.
- •Individuals who have received immunomodulatory, immunostimulatory, or immunosuppressant drugs within 3 months of Screening; or individuals requiring systemic corticosteroids exceeding 10 mg/day of prednisone equivalent for ≥10 days within 30 days of Screening.
- •Individuals who have received immunoglobulins and/or any blood or blood products within the 3 months before the first vaccine administration or plan to receive such products at any time during the study.
- •Individuals with a documented history of HIV infection, or who are currently known to have active tuberculosis.
- •Individuals receiving treatment with another investigational drug, biological agent, or device.
- •Individuals who have received any investigational COVID-19 vaccines.
- •Individuals who received any influenza vaccine within 6 months prior to enrollment or plan to receive an influenza vaccine during the study period.
- •Individuals who have received any other licensed vaccines within 14 days prior to enrollment in this study or who are planning to receive any vaccine up to 14 days after the study vaccination.
- •Individuals who are investigator site staff members, employees of the Sponsor or the Clinical Research Organization directly involved in the conduct of the study, or site staff members otherwise supervised by the investigator or immediate family members of any of the previously mentioned individuals.
研究组 & 干预措施
Group 1a (ARCT-2303/Influenza vaccine)
Participants will receive one 0.5-mL IM (intramuscular) dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29.
干预措施: ARCT-2303 (Biological)
Group 1a (ARCT-2303/Influenza vaccine)
Participants will receive one 0.5-mL IM (intramuscular) dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29.
干预措施: Influenza vaccine (Biological)
Group 1a (ARCT-2303/Influenza vaccine)
Participants will receive one 0.5-mL IM (intramuscular) dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29.
干预措施: Placebo (Other)
Group 2a (ARCT-2303)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29.
干预措施: ARCT-2303 (Biological)
Group 2a (ARCT-2303)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29.
干预措施: Influenza vaccine (Biological)
Group 2a (ARCT-2303)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29.
干预措施: Placebo (Other)
Group 3a (Influenza vaccine)
Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29.
干预措施: ARCT-2303 (Biological)
Group 3a (Influenza vaccine)
Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29.
干预措施: Influenza vaccine (Biological)
Group 3a (Influenza vaccine)
Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29.
干预措施: Placebo (Other)
Group 1b (ARCT-2303/ Influenza vaccine)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29.
干预措施: ARCT-2303 (Biological)
Group 1b (ARCT-2303/ Influenza vaccine)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29.
干预措施: Influenza vaccine, adjuvanted (Biological)
Group 1b (ARCT-2303/ Influenza vaccine)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of influenza vaccine on Day 1 followed by a 0.5-mL IM dose of placebo on Day 29.
干预措施: Placebo (Other)
Group 2b (ARCT-2303)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29.
干预措施: ARCT-2303 (Biological)
Group 2b (ARCT-2303)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29.
干预措施: Influenza vaccine, adjuvanted (Biological)
Group 2b (ARCT-2303)
Participants will receive one 0.5-mL IM dose of ARCT-2303 and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of influenza vaccine on Day 29.
干预措施: Placebo (Other)
Group 3b (Influenza vaccine)
Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29.
干预措施: ARCT-2303 (Biological)
Group 3b (Influenza vaccine)
Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29.
干预措施: Influenza vaccine, adjuvanted (Biological)
Group 3b (Influenza vaccine)
Participants will receive one 0.5-mL IM dose of influenza vaccine and one 0.5-mL IM dose of placebo on Day 1 followed by a 0.5-mL IM dose of ARCT-2303 on Day 29.
干预措施: Placebo (Other)
结局指标
主要结局
Groups 2a and 2b and ARCT-154-J01 Historical Control: Geometric Mean Titers (GMT) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibody Titers Against Omicron XBB.1.5 Subvariant at Day 29
时间窗: Day 29
Groups 2a and 2b and ARCT-154-J01 Historical Control: Number of Participants With Seroconversion to SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29
时间窗: Day 29
Seroconversion was defined as either a pre-vaccination titer below the lower limit of quantitation (LLOQ) and a postvaccination titer ≥4xLLOQ; or a pre-vaccination titer ≥LLOQ and a ≥4-fold increase in post-vaccination titer.
Groups 1a and 3a: Adjusted Hemagglutination Inhibition (HI) GMTs Against Influenza Vaccine Strains at Day 29
时间窗: Day 29
Influenza vaccine strains were A/H1N1, A/H3N2, B/Victoria, and B/Yamagata.
Groups 1a and 2a: Adjusted GMTs of SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant at Day 29
时间窗: Day 29
次要结局
- Groups 1a and 2a: GMT of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181(Group 1a: Days 1 and 29; Group 2a: Days 1, 29, and 181)
- Groups 1a and 2a: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181(Group 1a: Day 29; Group 2a: Days 29 and 181)
- Groups 1a and 2a: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29(Day 29)
- Groups 1a and 2a: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29(Days 1 and 29)
- Groups 1a and 3a: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29(Days 1 and 29)
- Groups 1a and 3a: GMFR of HI Assay Titers Against Influenza Vaccine Strains at Day 29(Day 29)
- Groups 1a and 3a: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29(Day 29)
- Groups 1a and 3a: Number of Participants With HI Titer ≥1:40 at Days 1 and 29(Days 1 and 29)
- Groups 1b and 2b: GMTs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 1, 29 and 181(Group 1b: Days 1 and 29, Group 2b: Days 1, 29 and 181)
- Groups 1b and 2b: GMFRs of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Days 29 and 181(Group 1b: Day 29 and Group 2b: Days 29 and 181)
- Groups 1b and 2b: Number of Participants With Seroconversion of SARS-CoV-2 Neutralizing Antibodies Against Omicron XBB.1.5 Subvariant at Day 29(Day 29)
- Groups 1b and 2b: Number of Participants With SARS-CoV-2 Neutralizing Antibody Against Omicron XBB.1.5 Subvariant Titer ≥ LLOQ at Days 1 and 29(Days 1 and 29)
- Groups 1b and 3b: GMTs of HI Assay Titers Against Influenza Vaccine Strains at Days 1 and 29(Days 1 and 29)
- Groups 1b and 3b: GMFRs of of HI Assay Titers Against Influenza Vaccine Strains at Day 29(Day 29)
- Groups 1b and 3b: Number of Participants With Seroconversion of HI Assay Titers Against Influenza Vaccine Strains at Day 29(Day 29)
- Groups 1b and 3b: Number of Participants With HI Titer ≥1:40 at Days 1 and 29(Days 1 and 29)
- Number of Participants With Local and Systemic Adverse Events (AEs)(Day 8 and Day 36 (up to 7 days after each study vaccination))
- Number of Participants With Unsolicited AEs(Up to Day 29 (Up to 28 days after first study vaccination) and up to Day 57 (28 days after second study vaccination))
- Number of Participants With Serious Adverse Events (SAEs), AEs Leading to Early Termination From Study, Medically Attended Adverse Event (MAAEs), and Adverse Event of Special Interest (AESIs)(Day 1 up to Day 181)