A Phase 2, Multicenter, Double-Blind, Randomized, Controlled Trial of the Safety and Immunogenicity of a Self-Amplifying mRNA COVID-19 Vaccine in Adult Hematopoietic Cell Transplant Recipients
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Geometric mean titer (GMT) of neutralizing antibody (nAb) against spike protein matching the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant
概览
简要总结
This phase IIb trial compares the effect of LUNAR-COV19 vaccine to Comirnaty vaccine in treating adult patients who have received a hematopoietic cell transplant (HCT). Guidelines recommend repeating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination of 3 messenger ribonucleic acid (mRNA) vaccines followed by a fourth booster 3-6 months after treatment. However, vaccination is less effective in HCT patients compared to healthy people due to impaired immune responses. LUNAR-COV19, a self-amplifying mRNA vaccine, may help the body's own immune system recognize the SARS-CoV-2 spike protein and fight the virus by using a special mRNA that copies itself for a stronger response. Vaccines made from mRNA with SARS-CoV-2, such as Comirnaty, may help the body build an effective immune response. This may provide active protection against SARS-CoV-2 infection. LUNAR-COV19 may be safe and tolerable and may generate a better and more durable immune response than the Comirnaty vaccine in adult patients who have received a HCT.
详细描述
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive LUNAR-COV19 intramuscularly (IM) on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
ARM II: Patients receive SARS-CoV-2 Comirnaty IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
After completion of study treatment, patients are followed up at days 115, 120, 127, 141 and 281.
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
- Double (Participant, Investigator)
盲法说明
Participants will be blinded to the treatment assignment, All investigative study center personnel involved in participant evaluations will remain blinded to the treatment assignments
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years
- •Willing and able to provide written informed consent, or with a legal representative who can provide informed consent (where locally approved)
- •Have received an allogeneic HCT within the prior 365 days
- •Have no relapse or progression of underlying malignancy
- •Have platelets ≥ 30,000/mm\^3
- •Not pregnant (confirmed with negative urine or serum pregnancy test, if applicable)
- •Willingness to take study vaccine and complete necessary study procedures
- •If of childbearing potential, must agree to use a highly effective method of birth control or abstain from heterosexual activity for the course of the study through at least 60 days after the last dose of the study vaccine
排除标准
- •Current infection with SARS-CoV-2 or infection within the prior 28 day period
- •Positive for SARS-CoV-2 by nasal swab polymerase chain reaction (PCR) at screening
- •Currently receiving any approved, authorized, or investigational direct-acting antiviral drug against SARS-CoV-2
- •Received any approved, authorized, or investigational monoclonal anti-SARS-CoV-2 antibody therapy within the prior 180 days before screening
- •Received a SARS-CoV-2 vaccine after HCT or within 28 days prior to HCT
- •Participation in any other concurrent clinical trial of an experimental treatment or prevention for SARS-CoV-2
- •Receiving \> 1 mg/kg/day corticosteroids within the prior 7 days
- •Active infection that is not adequately controlled, as determined by the investigator
- •Have received therapies that cause profound T-cell or B-cell depletion within 30 days of enrollment, or anticipated to receive such therapies within 3 months of enrollment
- •Have received immunoglobulin replacement therapy (IGRT) within 30 days of enrollment, or anticipated to receive IGRT within 3 months of enrollment
研究组 & 干预措施
Arm I (LUNAR-COV19)
Patients receive LUNAR-COV19 IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
干预措施: SARS-CoV-2 mRNA Vaccine ARCT-021 (Biological)
Arm I (LUNAR-COV19)
Patients receive LUNAR-COV19 IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (LUNAR-COV19)
Patients receive LUNAR-COV19 IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
干预措施: Electronic Health Record Review (Other)
Arm I (LUNAR-COV19)
Patients receive LUNAR-COV19 IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
干预措施: Survey Administration (Other)
Arm II (Comirnaty)
Patients receive SARS-CoV-2 Comirnaty IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
干预措施: Tozinameran (Biological)
Arm II (Comirnaty)
Patients receive SARS-CoV-2 Comirnaty IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (Comirnaty)
Patients receive SARS-CoV-2 Comirnaty IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
干预措施: Electronic Health Record Review (Other)
Arm II (Comirnaty)
Patients receive SARS-CoV-2 Comirnaty IM on days 1, 29 and 113 in the absence of medical conditions or unacceptable toxicity. Additionally, patients undergo nasal swab at screening and at time of suspected SARS-CoV-2 infection, as well as blood sample collection throughout the study.
干预措施: Survey Administration (Other)
结局指标
主要结局
Geometric mean titer (GMT) of neutralizing antibody (nAb) against spike protein matching the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant
时间窗: At 28 days after the third vaccine dose, assessed up through day 141
Will compare log10-transformed SARS-CoV-2 nAb titers at 28 days following the third vaccination (day 141) between study arms using linear mixed effects models with fixed effects for time points when nAb titers are measured up until day 141 (days 29, 113, and 141; baseline as the reference category), study arm, the interaction between time points and study arm, and stratification variables (time since hematopoietic cell transplantation \[HCT\] and site). Subject-specific random effects will be included. Model estimates will be exponentiated and presented as a ratio of GMTs, with 90% confidence intervals, to correspond with the two-sided alpha of 0.10 used for power calculations.
次要结局
- Percentage of participants with one or more solicited local or systemic reactogenicity signs and symptoms(For up to 7 days following each vaccination)
- Percentage of participants with unsolicited adverse events (AEs)(Up to 28 days following each vaccination)
- Percentage of participants with one or more serious AEs, or AEs of special interest (AESIs)(Following first study vaccine dose until 6 months following last vaccination)
- nAb GMT against spike protein matching the SARS-CoV-2 variant included in the vaccine(At 28-84 days after each vaccine dose, and at 6 months after the last dose)
- Anti-spike immunoglobulin G GMT against Spike protein matching the SARS-CoV-2 variant included in the vaccine(At 28-84 days after each vaccine dose, and at 6 months after the last dose)
- Seroresponse rates(At 28-84 days after each vaccine dose, and at 6 months after the last dose)
- Quantitative levels of anti-Spike T cell responses(At 28-84 days after each vaccine dose, and at 6 months after the last dose)
- New events of late-acute or chronic graft-versus-host disease (GVHD) of grade 3 or higher(Up to day 141)