A Synthetic MVA-based SARS-CoV-2 Vaccine, COH04S1, for the Prevention of COVID-19

Overview

This phase I trial evaluates the side effects and best dose of COH04S1, a synthetic modified vaccinia Ankara (MVA)-based SARS-CoV-2 vaccine, for the prevention of COVID-19. COVID-19 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. COH04S1 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 this study is to determine the safety and the optimal dose of the COH04S1 vaccine.

Full Title of Study: “Phase 1 Dose Escalation Study to Evaluate the Safety and Biologically Effective Dose of COH04S1, a Synthetic MVA-Based SARS-CoV-2 Vaccine, Administered as One or Two Injections to Healthy Adult Volunteers”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: November 10, 2022

Detailed Description

PRIMARY OBJECTIVE: I. Safety and tolerability of the COH04S1 vaccine at three different dose levels (DL): 1.0x10e7 plaque-forming unit (PFU)/dose, 1.0x10e8 PFU/dose, and 2.5x10e8 PFU/dose. SECONDARY OBJECTIVES: I. Longitudinal evaluation of humoral immunity. II. Quality and properties of cellular and humoral immunity elicited as a result of the vaccination. III. Explore the role of two injections versus one injection, and evaluate a placebo group. EXPLORATORY OBJECTIVE: I. Surveillance for incidental coronavirus disease 2019 (COVID-19) during follow-up (1 year). OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 3 arms. ARM I: Participants receive COH04S1 intramuscularly (IM) in the non-dominant upper arm on day 0 and day 28 in the absence of unacceptable toxicity. ARM II: 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. ARM III: Participants receive placebo IM in the non-dominant upper arm on day 0 and day 28 in the absence of unacceptable toxicity. Participants are followed up at 7, 14, 35, 42, 56, 90, 120, 180, 270, and 365 days.

Interventions

  • Drug: Placebo Administration
    • Given IM in the non-dominant upper arm
  • Biological: Vaccine Therapy
    • Given COH04S1 IM in the non-dominant upper arm

Arms, Groups and Cohorts

  • Experimental: Arm I (COH04S1)
    • Participants receive COH04S1 IM in the non-dominant upper arm on day 0 and day 28 in the absence of unacceptable toxicity.
  • Active Comparator: Arm II (COH04S1, placebo)
    • 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.
  • Placebo Comparator: Arm III (placebo)
    • Participants receive placebo IM in the non-dominant upper arm on day 0 and day 28 in the absence of unacceptable toxicity.

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of adverse events
    • Time Frame: Up to 365 days
    • Evaluated based on the Division of Microbiology and Infectious Diseases criteria.

Secondary Measures

  • Humoral immunity
    • Time Frame: During 1 year of observation
    • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific IgA, IgG, and IgM measured in serum and saliva by enzyme-linked immunosorbent assay.
  • Level of SARS-CoV-2-specfic neutralizing antibodies
    • Time Frame: Up to 365 days
    • Level of neutralizing antibodies and percentage of participants with neutralizing antibodies as determined by a pseudotyped lentivirus-S assay.
  • Th1 vs Th2 polarization
    • Time Frame: Up to 365 days
    • SARS-CoV-2-specific IFN-gamma, TNF-alpha, IL-2, IL-4, IL6, IL-13 cytokine levels will be measured to assess Th1 vs Th2 polarization.
  • SARS-CoV-2- antigen specific T cell responses to the COH04S1 vaccine
    • Time Frame: Up to 365 days
    • Percentage of participants with T cell immunity to SARS-CoV-2 S and N proteins post vaccination.
  • 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
    • Time Frame: Up to 365 days
    • Percentage of participants with activated/cycling and memory phenotype markers on the surface of SARS-CoV-2- specific T cells elicited as a result of the COH04S1 vaccination
  • Comparison of one vaccine injection vs two vaccine injections for immunogenicity
    • Time Frame: Up to 365 days
    • Immunogenicity will be evaluated based on the percentage of participants with SARS-CoV-2 S and N antibodies and T cell immunity post vaccination.
  • Comparison of one vaccine injection vs two vaccine injections for adverse events
    • Time Frame: Up to 365 days
    • Safety will be evaluated based on the Division of Microbiology and Infectious Diseases criteria.

Participating in This Clinical Trial

Inclusion Criteria

  • Documented informed consent of the participant – Ability to read and understand English or Spanish for questionnaires – Platelets >= 100,000/mm^3 (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – White blood cells (WBCs) 4,500-11,000/mm^3 (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Total bilirubin < 1.1 x upper limit of normal (ULN) (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Aspartate aminotransferase (AST) < 1.5 x ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Alanine aminotransferase (ALT) < 1.5 x ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Alkaline phosphatase (AP) < 1.1 x ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Blood urea nitrogen (BUN) < 1.25 x ULN (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Creatinine normal (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Sodium 137-145 mEq/L (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Potassium 3.5-5.1 mEq/L (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Carbon dioxide 22-30 mmol/L (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Glucose 60-100 mg/dL (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Lactate dehydrogenase (LDH) 140-271 U/L (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Albumin 3.5-5.0 g/dL (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Hemoglobin (HGB) > 10.5 gm/dL (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – Hematocrit (Hct) (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – For females: 34.4-44.6 % – For males: 37.6-47.2 % – 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 – Meets other institutional and federal requirements for infectious disease titer requirements – Note: Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy – Seronegative and viremia negative for SARS-CoV2 (within 30 days prior to day 0 of protocol therapy unless otherwise stated) – The viremic test will be performed at City of Hope (COH) on nasal wash samples using the Diasorin Simplexa test – The serologic test will be performed at TGen using the InBios assay – 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) – 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 – 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) Exclusion Criteria:
  • Subjects at increased risk of exposure to SARS-CoV-2, such as patient-facing health care workers and emergency responders are excluded – Subjects 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 – Subjects using investigational or licensed agents that may prevent or treat SARS-CoV-2 are excluded – Subjects 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 – 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 – Surgery in past 6 months that required general anesthesia. Minor procedures, such as dental surgery and superficial diagnostic biopsies, are permitted – No diagnosis which has been associated with immunodeficiency – 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. – Subjects 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 – Treatment with medication for high cholesterol or other lipid abnormality – History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent – History of adverse event with a prior smallpox vaccination – 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 – Subjects 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.) – Subjects with severe migraine headaches (more than one per month on average in the past 6 months or requiring preventive medication) are excluded – History of heart disease, e.g. previous treated arrhythmia or myocardial infarction – Horizontal positioning- induced or activities of normal living exercise-induced shortness of breath – History of stroke or claudication – 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. – Poxvirus vaccine in the last 12 months – Any MVA vaccine, or treatment with whole or subunit SARS-CoV-2 or poxvirus vaccine in the last 12 months – History of or prior treatment for diabetes type 1 or diabetes type 2; BMI < 18 or > 30 – Clinically significant uncontrolled illness – Active infection requiring treatment – Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection – Diagnosis which has been associated with immunodeficiency – Females only: Pregnant or breastfeeding – 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 – Subjects 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 – 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
  • Gender Eligibility: All

    Minimum Age: 18 Years

    Maximum Age: 55 Years

    Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

    Investigator Details

    • Lead Sponsor
      • City of Hope Medical Center
    • Collaborator
      • National Cancer Institute (NCI)
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • John Zaia, Principal Investigator, City of Hope Medical Center

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