A Phase 2 Randomized, Multi-center Study of GEO-CMO4S1 (SARS-CoV-2 Vaccine) Versus mRNA SARS-CoV-2 Vaccine in Patients Post Cellular Therapy for Hematological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- GeoVax, Inc.
- 入组人数
- 63
- 试验地点
- 6
- 主要终点
- Biological response
研究概览
简要总结
This phase 2 trial studies the immune response to GEO-CM04S1 (previously designated as COH04S1) compared to standard of care (SOC) mRNA SARS-COV-2 vaccine in patients with blood cancer who have received stem cell transplant or cellular therapy.
GEO-CM04S1 belongs to a category called modified vaccinia Ankara (MVA) vaccines, created from a new version of MVA, called synthetic MVA. GEO-CM04S1 works by inducing immunity (the ability to recognize and fight against an infection) to SARS-CoV-2. The immune system is stimulated to produce antibodies against SARS-CoV-2 that would block the virus from entering healthy cells. The immune system also grows new disease fighting T cells that can recognize and destroy infected cells. Giving GEO-CM04S1 after cellular therapy may work better in reducing the chances of contracting coronavirus disease 2019 (COVID-19) or developing a severe form of COVID-19 disease in patients with blood cancer compared to SOC mRNA SARS-CoV-2 vaccine.
详细描述
PRIMARY OBJECTIVE:
I. Evaluate the biological activity and the role of timing of 2 injections of GEO-CM04S1 vaccine administered at 2.5e8 PFU/dose compared to SOC mRNA vaccine.
SECONDARY OBJECTIVES:
I. Assess safety of GEO-CM04S1 vaccine. II. Evaluation of SARS-CoV-2 S and N-specific Th1 vs Th2 polarization. III. Evaluate T-cell levels and function. IV. Evaluate activated/cycling and memory phenotype markers. V. Evaluate durability of immune responses. VI. Evaluate maintenance of immunity that can be associated with protection over the study period.
EXPLORATORY OBJECTIVE:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (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
- 否
入选标准
- •Documented informed consent of the participant
- •Age >=18 years
- •Eastern Cooperative Oncology Group (ECOG) =<1
- •Allogeneic or autologous hematopoietic cell transplant (HCT), cellular therapy (chimeric antigen receptor [CAR] T-cell) recipients who are at >= 3 months of infusion date of respective regimen
- •Platelets >= 50,000/mm^3 (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •White blood cells (WBCs) >= 1000/mm^3 (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •Total bilirubin < 1.5 X upper limit of normal (ULN) (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •Aspartate aminotransferase (AST) < 2.5 X ULN (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •Alanine aminotransferase (ALT) < 2.5 X ULN (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •Creatinine < 1.5 X ULN (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •Negative COVID-19 PCR test
- •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed within 30 days prior to day 0 of protocol therapy unless otherwise stated). If the urine pregnancy test is inconclusive a serum pregnancy test will be required
- •Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 weeks after the last dose of protocol therapy
- •Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
排除标准
- •Systemic corticosteroids required for chronic conditions at doses > 0.5mg/kg/day prednisone equivalent within 7 days of enrollment
- •Prior Evusheld or other anti-SARS CoV-2 prophylaxis < 2 weeks prior to enrollment
- •Therapies that cause profound T-cell or B cell depletion within 30 days of enrollment
- •Maintenance therapies (e.g. rituximab, Bruton tyrosine kinase inhibitors, Janus kinase inhibitors) within 30 days of enrollment
- •Received investigational or licensed SARS-CoV-2 vaccines after their qualifying cellular therapy. Patients who received a SARS- CoV-2 vaccine prior to cellular therapy are eligible for this trial, as revaccination for these patients (e.g. flu and shingles vaccine) is standard of care.
- •Received a live vaccine ≤30 days prior to administration of study vaccine or subjects who are =< 2 weeks within administration of inactivated vaccines (e.g. influenza vaccine). Flu shots are allowed > 2 weeks before the first injection and > 2 weeks post 2nd injection
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to vaccine agents
- •History of adverse event with a prior smallpox vaccination
- •Any MVA vaccine or poxvirus vaccine in the last 12 months
- •History (suspected or confirmed) of myocarditis or pericarditis
- •Clinically significant uncontrolled illness
- •Females only: Pregnant or breastfeeding
- •Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
- •Anyone considered to be in a vulnerable population as defined in 45 CFR §46.111 (a)(3) and 45 CFR §46, Subparts B-D
研究组 & 干预措施
Arm I (GEO-CM04S1)
Patients receive one dose of GEO-CM04S1 IM in the upper arm on days 0 and 28.
干预措施: Diagnostic Laboratory Biomarker Analysis (Other)
Arm I (GEO-CM04S1)
Patients receive one dose of GEO-CM04S1 IM in the upper arm on days 0 and 28.
干预措施: Synthetic MVA-based SARS-CoV-2 Vaccine GEO-CM04S1 (Biological)
Arm II (SOC mRNA SARS-CoV-2 vaccine)
Patients receive one dose of SOC mRNA SARS-CoV-2 vaccine IM in the upper arm on days 0 and 28.
结局指标
主要结局
Biological response
时间窗: At 28 days post the second vaccine injection
Based on at least a 3-fold increase in severe acute respiratory syndrome coronavirus 2 (SARSCoV-2)- neutralizing antibodies or interferon (IFN)-gamma levels. Will compare the immune response at day 28 post the second injection between GEO-CM04S1 and SOC mRNA SARS-CoV-2 vaccine using a one-sided stratified Cochran-Mantel-Haenszel test. The point estimate and 95% confidence interval will be calculated per arm for immune response at day 28 post the second injection. Bar charts will be generated to show the immune response rate by arm overall, and by arm and strata.
次要结局
- Incidence of graft-versus-host disease (GVHD)(Up to 365 days)
- Percentages of activated/cycling and memory phenotype markers on the surface of antigen-specific T cells(Up to 365 days)
- Incidence of moderate adverse events (AEs)(Up to 365 days)
- Incidence of unacceptable AEs(Up to 365 days)
- Non-relapse mortality(Up to 365 days)
- Incidence of Severe coronavirus disease 2019 (COVID-19)(Up to 365 days)
- Antigen specific T cell responses to the COH04S1 vaccine(Up to 365 days)
- Humoral immunity(Up to 365 days)
- Th1 vs Th2 polarization(Up to 365 days)
- Neutralizing antibodies(Up to 365 days)