NCT04639466已完成1 期
Phase 1/2 Dose Escalation Study To Evaluate the Safety and Biologically Effective Dose of GEO-CM04S1, a Synthetic MVA-based SARS-CoV-2 Vaccine, Administered as One or Two Injections or as a Booster to Healthy Adult Volunteers
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- GeoVax, Inc.
- 入组人数
- 119
- 试验地点
- 3
- 主要终点
- Incidence of adverse events (Phase I)
研究概览
简要总结
This phase I trial evaluates the side effects and best dose of GEO-CM04S1 (previously designated as COH04S1), a synthetic modified vaccinia Ankara (MVA)-based SARS-CoV-2 vaccine, for the prevention of COVID-19 infection. COVID-19 infection is caused by the SARS-CoV-2 virus. SARS-CoV-2 has demonstrated the capability to spread rapidly, leading to significant impacts on healthcare systems and causing societal disruption. GEO-CM04S1 was created by placing small pieces of SARS-CoV-2 DNA (the chemical form of genes) into synthetic MVA, which may be able to induce immunity (the ability to recognize and fight against an infection) to SARS-CoV-2. The purpose of the Phase 1 study is to determine the safety and the optimal dose of the GEO-CM04S1 vaccine.
The Phase 2 study is designed as a multi-center, double-blind, randomized, parallel, study to evaluate the safety profile of 2 dose levels of GEO-CM04S1 as a single booster shot to assess the immune response measured by the fold-increase in antibody against SARS-CoV-2 Spike protein at day 28 post-injection among healthy adult volunteers.
详细描述
PRIMARY OBJECTIVE:
I. Safety and tolerability of the synthetic MVA-based SARS-CoV-2 vaccine GEO-CM04S1 vaccine at three different dose levels (DL): 1.0x10^7 plaque-forming unit (PFU)/dose, 1.0x10^8 PFU/dose, and 2.5x10^8 PFU/dose. (Phase I)
II. Evaluate the safety profile of a single-dose vaccine boost at day 7 post-injection of GEO-CM04S1. (Phase II)
III. Determine whether the GEO-CM04S1 dose levels tested (1.0x10^7 or 1.0x10^8) generate promising immune responses (>5-fold increase of Spike IgG over baseline) after single-dose booster injection, and select a promising dose to use for further study. (Phase II)
SECONDARY OBJECTIVES:
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •PHASE I: Documented informed consent of the participant
- •PHASE I: Age: >= 18 years and < 55 years
- •PHASE I: Ability to read and understand English, Spanish, or Mandarin for consenting
- •PHASE I: Platelets >= 100,000/mm^3 (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: White blood cells (WBCs) 3,600-10,100/mm^3 (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Total bilirubin < 1.1 x upper limit of normal (ULN) (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Aspartate aminotransferase (AST) < 1.5 x ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Alanine aminotransferase (ALT) < 1.5 x ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Alkaline phosphatase (AP) < 1.1 x ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Blood urea nitrogen (BUN) < 1.25 x ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Creatinine less than or equal to the ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Sodium 137-145 mEq/L (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Potassium 3.5-5.1 mEq/L (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Carbon dioxide 22-30 mmol/L (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Glucose 80-128 mg/dL (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Albumin 3.5-5.0 g/dL (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Hemoglobin (HGB) > 10.5 gm/dL (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Hematocrit (Hct) (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •For females: 34.5-44.6 %
- •For males: 37.6-47.2 %
- •PHASE I: Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
- •PHASE I: History negative for COVID-19 and nasopharyngeal test results pending for SARS-CoV2 performed at City of Hope (COH) on nasal wash samples using the Diasorin Simplexa test (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •Baseline SARS-CoV2serologic test will be performed at TGen using the InBios assay; the result will not be required for eligibility
- •PHASE I: A documented electrocardiogram (ECG) and cardiac troponin must be within normal institutional limits in the past 30 days; "normal ECG with sinus tachycardia" or "normal ECG with sinus bradycardia" is allowable based on a history of absent cardiac/exercise related symptoms as determined by the principal investigator (P.I.) in consultation with a senior staff cardiologist (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE I: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •PHASE I: 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)
- •PHASE II: Prior COVID-19 mRNA vaccination with EUA or FDA-approved vaccine, >= 6 months prior
- •PHASE II: ECOG performance score 0-1
- •PHASE II: Documented informed consent of the participant
- •PHASE II: Age: >= 18 years
- •PHASE II: Platelets >= 100,000/mm^3 (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: WBCs 3,600-10,100/mm^3 (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: Total bilirubin < 1.1 X ULN (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: AST < 1.5 x ULN (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: ALT < 1.5 x ULN (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: AP < 1.1 x ULN (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: BUN < 1.25 x ULN (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: Creatinine less than or equal to the ULN (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: Sodium 137-145 mEq/L (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: Potassium 3.5-5.1 mEq/L (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: Carbon dioxide 22-30 mmol/L (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: Glucose 80-128 mg/dL (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: Albumin 3.5-5.0 g/dL (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: HGB > 10.5 gm/dL (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •PHASE II: Hematocrit (Hct) (performed within 30 days prior to day 0 of protocol therapy unless otherwise stated)
- •For females: 34.5-44.6 %
- •For males: 37.6-47.2 %
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排除标准
- •PHASE I: Participants at increased risk of exposure to SARS-CoV-2, such as patient-facing health care workers and emergency responders are excluded
- •PHASE I: Participants who would be at higher risk for severe COVID-19 according to known risk factors are excluded e.g. type 2 diabetes, obesity (body mass index [BMI] >= 35), congestive heart failure (New York Heart Association class >= I), history of coronary artery disease, or chronic obstructive pulmonary disease
- •PHASE I: Participants using investigational or licensed agents that may prevent or treat SARS-CoV-2 are excluded
- •PHASE I: Participants are excluded, who have any history of allergic diatheses as defined by a history of asthma, anaphylaxis, or generalized urticaria, or by daily use of antihistamines, episodic (more than once in past 3 months) inhalational medications including steroidal agents, non-steroidal agents, or cromolyn sodium
- •PHASE I: Any previous condition, or one that becomes known during the screening period, which would suggest that the technicians and health professionals involved in the study would be exposed to specific infectious risk
- •PHASE I: Surgery in past 6 months that required general anesthesia. Minor procedures, such as dental surgery and superficial diagnostic biopsies, are permitted
- •PHASE I: Taking daily medications for chronic or intercurrent illness. Medications excluded from this rule are: thyroid replacement, estrogen replacement, dietary vitamins and protein supplements, mild anti-depressant and anxiety medication, and any medication not known or likely to be immunosuppressive, as determined by the P.I.
- •PHASE I: Participants who have had 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
- •PHASE I: Treatment with medication for high cholesterol or other lipid abnormality. Prophylactic medication is acceptable
- •PHASE I: History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
- •PHASE I: History of adverse event with a prior smallpox vaccination
- •PHASE I: Any previous condition, or one that becomes known during the screening period, that would suggest that the individual could be immunologically impaired, or for which this study would pose a danger to him/herself or about which the P.I., in evaluating the subject for eligibility, determines that this exclusion is appropriate
- •PHASE I: Participants are excluded who have history of cancer other than basal cell skin cancer, or any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc. as determined by the P.I.)
- •PHASE I: Participants with severe migraine headaches (more than one per month on average in the past 6 months or requiring preventive medication) are excluded but those on effective medication (less than one migraine per month) are allowed to enroll
- •PHASE I: History of heart disease, e.g. previous treated arrhythmia or myocardial infarction
- •PHASE I: Horizontal positioning- induced or activities of normal living exercise-induced shortness of breath
- •PHASE I: History of stroke or claudication
- •PHASE I: Any of the following cardiac findings of ECG abnormality: 1) conduction disturbance (complete left or right bundle branch block, intraventricular conduction disturbance with QRS > 120 ms, atrioventricular block [AV] block of any degree, and corrected QT [QTc] prolongation > 450 msec for men and > 460 msec for women); 2) repolarization (ST segment or T wave) abnormality; 3) significant atrial or ventricular arrhythmia, including frequent ectopy (e.g., 2 premature ventricular contractions in a row); and 4) evidence of past myocardial infarction.
- •PHASE I: Poxvirus vaccine in the last 12 months
- •PHASE I: Any MVA vaccine or poxvirus vaccine in the last 12 months
- •PHASE I: Any previous SARS-CoV-2 vaccine
- •PHASE I: History of or prior treatment for diabetes type 1 or diabetes type 2; BMI < 18 or >
- •BMI can be rounded to the nearest integer
- •PHASE I: Clinically significant uncontrolled illness
- •PHASE I: Active infection requiring treatment
- •PHASE I: Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
- •PHASE I: Diagnosis which has been associated with immunodeficiency
- •PHASE I: Females only: Pregnant or breastfeeding
- •PHASE I: Men with partners of child-bearing potential and women of children-bearing potential who are not willing to use medically effective birth control methods, e.g. contraceptive pill, condom, or diaphragm, and continue this for 6 weeks after the second and last dose of vaccine
- •PHASE I: Participants who are employed by or are a student at City of Hope and are in a chain of command that reports directly to persons listed on the protocol as principal investigator or co-investigators; or are relatives or partners of the investigators
- •PHASE I: 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
- •PHASE I: 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)
- •PHASE I: Anyone considered to be in a vulnerable population as defined in 45 CFR 46.111 (a)(3) and 45 CFR 46, Subparts B-D
- •PHASE II: Participants who would be at higher risk for severe COVID-19 according to known risk factors are excluded e.g. type 2 diabetes, obesity (BMI > 35), congestive heart failure (New York Heart Association Class >= I), history of coronary artery disease, cardiomyopathies, sickle cell disease, smoking, chronic kidney disease, immunocompromised state from solid organ transplant, or chronic obstructive pulmonary disease, or active cancers other than basal cell skin cancer at discretion of the investigator.
- •PHASE II: Participants are excluded, who have any history of allergic diatheses as defined by a history of asthma, anaphylaxis, or generalized urticaria, episodic (more than once in past 3 months) inhalational medications including steroidal agents, non-steroidal agents, or cromolyn sodium
- •PHASE II: Any previous condition, or one that becomes known during the screening period, which would suggest that the technicians and health professionals involved in the study would be exposed to specific infectious risk
- •PHASE II: Taking daily medications for chronic or intercurrent illness. Medications excluded from this rule are: thyroid replacement, estrogen replacement, dietary vitamins and protein supplements, mild anti-depressant and anxiety medication, and any medication not known or likely to be immunosuppressive, as determined by the P.I.
- •PHASE II: Participants who have had a live vaccine =< 30 days prior to administration of study vaccine or participants who are =< 2 weeks within administration of inactivated vaccines (e.g. influenza vaccine). Flu shots are allowed > 2 weeks before the booster injection and > 2 weeks post booster injection
- •PHASE II: Intensive cytotoxic therapies, B- or T-cell depleting therapies, or checkpoint inhibitors within 30 days of enrollment
- •PHASE II: Systemic corticosteroids required for chronic conditions at doses > 0.5 mg/kg/day prednisone equivalent within 14 days of enrollment
- •PHASE II: Previously received a COVID-19 vaccine booster injection
- •PHASE II: History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
- •PHASE II: History (suspected or confirmed) of myocarditis or pericarditis
- •PHASE II: History of adverse event with a prior smallpox vaccination
- •PHASE II: Any previous condition, or one that becomes known during the screening period, that would suggest that the individual could be immunologically impaired, or for which this study would pose a danger to him/herself or about which the P.I., in evaluating the participant for eligibility, determines that this exclusion is appropriate.
- •PHASE II: Participants are excluded who have any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc. as determined by the P.I.)
- •PHASE II: Participants with severe migraine headaches (more than one per month on average in the past 6 months or requiring preventive medication) are excluded but those on effective medication (less than one migraine per month) are allowed to enroll.
- •PHASE II: History of heart disease, e.g. previous treated arrhythmia or myocardial infarction
- •PHASE II: History of stroke or claudication.
- •PHASE II: Any MVA vaccine or poxvirus vaccine in the last 12 months;
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研究组 & 干预措施
Phase I Arm I (COH04S1)
Experimental
Participants receive COH04S1 IM in the non-dominant upper arm on day 0 and day 28 in the absence of unacceptable toxicity.
干预措施: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1 (Biological)
Phase I Arm II (COH04S1, placebo)
Active Comparator
Participants receive COH04S1 IM in the non-dominant upper arm on day 0 and placebo IM in the non-dominant upper arm on day 28 in the absence of unacceptable toxicity.
干预措施: Placebo Administration (Drug)
Phase I Arm II (COH04S1, placebo)
Active Comparator
Participants receive COH04S1 IM in the non-dominant upper arm on day 0 and placebo IM in the non-dominant upper arm on day 28 in the absence of unacceptable toxicity.
干预措施: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1 (Biological)
Phase I Arm III (placebo)
Placebo Comparator
Participants receive placebo IM in the non-dominant upper arm on day 0 and day 28 in the absence of unacceptable toxicity.
干预措施: Placebo Administration (Drug)
Phase II Arm I (low dose COH04S1 booster)
Experimental
Participants receive low dose COH04S1 booster IM in non-dominant upper arm on day 1 in the absence of unacceptable toxicity.
干预措施: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1 (Biological)
Phase II Arm II (high dose COH04S1 booster)
Experimental
Participants receive high dose COH04S1 booster IM in non-dominant upper arm on day 1 in the absence of unacceptable toxicity.
干预措施: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1 (Biological)
结局指标
主要结局
Incidence of adverse events (Phase I)
时间窗: Up to 365 days
Evaluated based on the Division of Microbiology and Infectious Diseases criteria.
Incidence of adverse events (Phase II)
时间窗: Within the first 7 days following booster injection
Evaluated based on the Division of Microbiology and Infectious Diseases criteria.
Fold increase of Spike IgG levels (Phase II)
时间窗: At 28 days post-injection
Antibody levels to SARS CoV-2 Spike protein (Phase II)
时间窗: Up to 365 days
Assessed by Ortho VITROS Anti-SARS-CoV-2 IgG Quantitative assay.
次要结局
- Level of SARS-CoV-2-specfic neutralizing antibodies (Phase I)(Up to 365 days)
- SARS-CoV-2- antigen specific T cell responses to the COH04S1 vaccine (Phase I)(Up to 365 days)
- Humoral immunity (Phase I)(During 1 year of observation)
- Th1 vs Th2 polarization (Phase I)(Up to 365 days)
- T lymphocyte production of cytokines in response to in vitro peptide library stimulation (Phase II)(Up to 365 days)
- COVID-19 disease that is moderate, severe, or critical (Phase II)(Up to 365 days)
- Evolution of activated/cycling and memory phenotype markers on the surface of SARS-CoV-2- specific T cells elicited as a result of the COH04S1 vaccination (Phase I)(Up to 365 days)
- Comparison of immunogenicity and adverse events (Phase I)(Up to 365 days)
- T lymphocyte production of cytokines in response to in vitro stimulation with overlapping peptide libraries specific for SARS-CoV-2 (Phase II)(Up to 365 days)
- SARS-CoV-2-S and -N specific IFNγ (Th1) and IL-4 (Th2) cytokine levels (Phase II)(Up to 365 days)
- Neutralizing Ab levels (Phase II)(Up to 365 days)
- Antibody to SARS CoV-2 Spike protein (Phase II)(Up to 365 days)
- Confirmed COVID-19 infection by PCR viral load (Phase II)(Up to 365 days)
- Moderna or Pfizer vaccine received previously (Phase II)(Up to 365 days)
研究者
研究点 (3)
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