Back to resultsSARS-CoV-2 Vaccine (COH04S1) Versus EUA SARS-COV-2 Vaccine for the Treatment of COVID-19 in Patients With Blood Cancer
Primary Purpose
COVID-19 Infection, Hematopoietic and Lymphoid System Neoplasm, Leukemia
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
COVID-19 Vaccine
Diagnostic Laboratory Biomarker Analysis
Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 Infection
Eligibility Criteria
Inclusion Criteria:
- Documented informed consent of the participant
- Age >=18 years
- Eastern Cooperative Oncology Group (ECOG) =< 2
- 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)
- 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)
Exclusion Criteria:
- Patients who have received second allogeneic HCT are not eligible (patients who have undergone a previous autologous HCT are eligible
- Systemic corticosteroids required for chronic conditions at doses > 0.5mg/kg/day prednisone equivalent
- Patients on maintenance therapies (e.g. rituximab, Bruton tyrosine kinase inhibitors, Janus kinase inhibitors), who may have significantly attenuated response to vaccination
- Subjects using investigational or licensed agents that may prevent or treat SARS-CoV-2 are excluded such as any previous SARS-CoV-2 vaccine
- 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
- 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
- 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
Sites / Locations
- City of Hope Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm I (COH04S1)
Arm II (EUA SARS-CoV-2 vaccine)
Arm Description
Patients receive one dose of COH04S1 IM in the upper arm on days 0 and 28.
Patients receive one dose of EUA SARS-CoV-2 vaccine IM in the upper arm on days 0 and 28.
Outcomes
Primary Outcome Measures
Biological response
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 COH04S1 and Emergency Use Authorization 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.
Secondary Outcome Measures
Incidence of moderate adverse events (AEs)
Will assess grade 2 AEs based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at least probably related to protocol treatment.
Incidence of unacceptable AEs
Will assess grade 3-5 AEs based on CTCAE version 5.0, at least probably related to protocol treatment.
Non-relapse mortality
Defined as death from any cause other than relapse of underlying hematologic malignancy recorded from the first injection to day 365 among all subjects.
Incidence of graft-versus-host disease (GVHD)
Will assess the incidence of moderate/severe chronic and late-onset grade III-IV acute GVHD among allogeneic hematopoietic cell transplantation recipients only.
Incidence of Severe coronavirus disease 2019 (COVID-19)
Will assess for confirmed COVID-19 infection with one of the following additional features from the first injection to day 365:
Clinical sign at rest indicative of severe systemic illness (respiratory rate >= 30 breaths per minute, heart rate >= 125 beats per minute, oxygen saturation =< 93% on room air at sea level, or partial pressure of oxygen/fraction of inspired oxygen < 300 mm Hg);
Respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation);
Evidence of shock (systolic blood pressure <90 mmHg, diastolic blood pressure < 60 mmHg, or requiring vasopressors);
Significant acute renal, hepatic, or neurologic dysfunction;
Admission to an intensive care unit;
Death
Th1 vs Th2 polarization
Will evaluate SARS-CoV-2-S and -N specific Th1 (IFN gamma ng/ml) and Th2 (IL-4 ng/ml) cytokine levels following stimulation with overlapping peptide libraries specific for SARSCoV-2. Will perform dual fluorescence ELISPOT assay to detect and quantify cells secreting IFN gamma and IL-4.
Antigen specific T cell responses to the COH04S1 vaccine
Assessed using overlapping S and N peptide libraries specific for SARS-CoV-2.
Percentages of activated/cycling and memory phenotype markers on the surface of antigen-specific T cells
In vaccine responders, SARS-CoV-2 specific T cells will be further evaluated by measuring levels percentages of CD137 surface marker expressed on CD3+ CD8+ and CD3+ CD4+ T cells stimulated for 24 hours with either SARS-CoV-2-S or SARS-CoV-2-N overlapping peptide libraries. Will also assess the activated/cycling phenotype percentages by using the CD38, HLA-DR, Ki67 and PD1 surface markers.
Humoral immunity
Will measure SARS-CoV-2 specific antibodies, including IgA, IgG, and IgM, in serum and saliva by enzyme linked immunosorbent assay (ELISA). Pools of SARS-CoV-2 convalescent serum or SARS-CoV-2 negative serum will be used as a positive- and negative-controls (University of California at San Diego), respectively. Antibody levels in recipients will be graphed on a time plot and compared to baseline level in donors.
Neutralizing antibodies
Will measure and isolate the generation of neutralizing antibodies in participants, and test whether they prevent infection of a susceptible cell line with a pseudo-type of the SARS-CoV-2 virus. Evaluation of SARS-CoV-2 neutralizing antibody titers in serum samples of COH04S1 vaccinated volunteers will be performed. Will use SARS-CoV-2 lentiviral pseudovirus expressing the Spike antigen and infecting 293T cell lines engineered to express ACE2. Spike incorporation into the pseudovirus will be verified and quantified by Western blot using Spike-specific antibodies and by ELISA.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04977024
Brief Title
SARS-CoV-2 Vaccine (COH04S1) Versus EUA SARS-COV-2 Vaccine for the Treatment of COVID-19 in Patients With Blood Cancer
Official Title
A Multi-Center, Observer-Blinded, EUA Vaccine-Controlled, Randomized Phase II Study to Evaluate the Biological Activity of COH04S1 (SARS-CoV-2 Vaccine) Compared to EUA SARS-CoV-2 Vaccines in Hematology Patients Who Have Received Cellular Therapy (HCT or CAR-T)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 27, 2021 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
January 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GeoVax, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase II trial studies the immune response to COH04S1 compared to Emergency Use Authorization (EUA) SARS-COV-2 vaccine in patients with blood cancer who have received stem cell transplant or cellular therapy.
COH04S1 belongs to a category called modified vaccinia Ankara (MVA) vaccines, created from a new version of MVA, called synthetic MVA. COH04S1 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 COH04S1 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 EUA SARS-CoV-2 vaccine.
Detailed Description
PRIMARY OBJECTIVE:
I. Evaluate the biological activity and the role of timing of 2 injections of COH04S1 vaccine administered at 2.5x10e8 PFU/dose compared to EUA vaccine.
SECONDARY OBJECTIVES:
I. Assess safety of COH04S1 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:
I. Surveillance for incidental COVID-19 infection during follow-up (1 year).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I : Patients receive one dose of COH04S1 intramuscularly (IM) in the upper arm on days 0 and 28.
ARM II : Patients receive one dose of EUA SARS-CoV-2 vaccine IM in the upper arm on days 0 and 28.
After the completion of study treatment, patients are followed up at days 7, 90, 120, 180, and 365.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Infection, Hematopoietic and Lymphoid System Neoplasm, Leukemia, Lymphoma, Plasma Cell Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
240 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm I (COH04S1)
Arm Type
Experimental
Arm Description
Patients receive one dose of COH04S1 IM in the upper arm on days 0 and 28.
Arm Title
Arm II (EUA SARS-CoV-2 vaccine)
Arm Type
Experimental
Arm Description
Patients receive one dose of EUA SARS-CoV-2 vaccine IM in the upper arm on days 0 and 28.
Intervention Type
Biological
Intervention Name(s)
COVID-19 Vaccine
Intervention Description
Receive EUA SARS-CoV-2 vaccine IM
Intervention Type
Other
Intervention Name(s)
Diagnostic Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1
Other Intervention Name(s)
COH04S1, SARS-CoV-2 Vaccine COH04S1, sMVA-based SARS-CoV-2 Vaccine COH04S1
Intervention Description
Given IM
Primary Outcome Measure Information:
Title
Biological response
Description
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 COH04S1 and Emergency Use Authorization 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.
Time Frame
At 28 days post the second vaccine injection
Secondary Outcome Measure Information:
Title
Incidence of moderate adverse events (AEs)
Description
Will assess grade 2 AEs based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at least probably related to protocol treatment.
Time Frame
Up to 365 days
Title
Incidence of unacceptable AEs
Description
Will assess grade 3-5 AEs based on CTCAE version 5.0, at least probably related to protocol treatment.
Time Frame
Up to 365 days
Title
Non-relapse mortality
Description
Defined as death from any cause other than relapse of underlying hematologic malignancy recorded from the first injection to day 365 among all subjects.
Time Frame
Up to 365 days
Title
Incidence of graft-versus-host disease (GVHD)
Description
Will assess the incidence of moderate/severe chronic and late-onset grade III-IV acute GVHD among allogeneic hematopoietic cell transplantation recipients only.
Time Frame
Up to 365 days
Title
Incidence of Severe coronavirus disease 2019 (COVID-19)
Description
Will assess for confirmed COVID-19 infection with one of the following additional features from the first injection to day 365:
Clinical sign at rest indicative of severe systemic illness (respiratory rate >= 30 breaths per minute, heart rate >= 125 beats per minute, oxygen saturation =< 93% on room air at sea level, or partial pressure of oxygen/fraction of inspired oxygen < 300 mm Hg);
Respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation);
Evidence of shock (systolic blood pressure <90 mmHg, diastolic blood pressure < 60 mmHg, or requiring vasopressors);
Significant acute renal, hepatic, or neurologic dysfunction;
Admission to an intensive care unit;
Death
Time Frame
Up to 365 days
Title
Th1 vs Th2 polarization
Description
Will evaluate SARS-CoV-2-S and -N specific Th1 (IFN gamma ng/ml) and Th2 (IL-4 ng/ml) cytokine levels following stimulation with overlapping peptide libraries specific for SARSCoV-2. Will perform dual fluorescence ELISPOT assay to detect and quantify cells secreting IFN gamma and IL-4.
Time Frame
Up to 365 days
Title
Antigen specific T cell responses to the COH04S1 vaccine
Description
Assessed using overlapping S and N peptide libraries specific for SARS-CoV-2.
Time Frame
Up to 365 days
Title
Percentages of activated/cycling and memory phenotype markers on the surface of antigen-specific T cells
Description
In vaccine responders, SARS-CoV-2 specific T cells will be further evaluated by measuring levels percentages of CD137 surface marker expressed on CD3+ CD8+ and CD3+ CD4+ T cells stimulated for 24 hours with either SARS-CoV-2-S or SARS-CoV-2-N overlapping peptide libraries. Will also assess the activated/cycling phenotype percentages by using the CD38, HLA-DR, Ki67 and PD1 surface markers.
Time Frame
Up to 365 days
Title
Humoral immunity
Description
Will measure SARS-CoV-2 specific antibodies, including IgA, IgG, and IgM, in serum and saliva by enzyme linked immunosorbent assay (ELISA). Pools of SARS-CoV-2 convalescent serum or SARS-CoV-2 negative serum will be used as a positive- and negative-controls (University of California at San Diego), respectively. Antibody levels in recipients will be graphed on a time plot and compared to baseline level in donors.
Time Frame
Up to 365 days
Title
Neutralizing antibodies
Description
Will measure and isolate the generation of neutralizing antibodies in participants, and test whether they prevent infection of a susceptible cell line with a pseudo-type of the SARS-CoV-2 virus. Evaluation of SARS-CoV-2 neutralizing antibody titers in serum samples of COH04S1 vaccinated volunteers will be performed. Will use SARS-CoV-2 lentiviral pseudovirus expressing the Spike antigen and infecting 293T cell lines engineered to express ACE2. Spike incorporation into the pseudovirus will be verified and quantified by Western blot using Spike-specific antibodies and by ELISA.
Time Frame
Up to 365 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Documented informed consent of the participant
Age >=18 years
Eastern Cooperative Oncology Group (ECOG) =< 2
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)
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)
Exclusion Criteria:
Patients who have received second allogeneic HCT are not eligible (patients who have undergone a previous autologous HCT are eligible
Systemic corticosteroids required for chronic conditions at doses > 0.5mg/kg/day prednisone equivalent
Patients on maintenance therapies (e.g. rituximab, Bruton tyrosine kinase inhibitors, Janus kinase inhibitors), who may have significantly attenuated response to vaccination
Subjects using investigational or licensed agents that may prevent or treat SARS-CoV-2 are excluded such as any previous SARS-CoV-2 vaccine
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
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chief Medical Officer
Phone
678-384-7220
Email
info@geovax.com
First Name & Middle Initial & Last Name or Official Title & Degree
Director Clinical Operations
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Medical Officer
Organizational Affiliation
GeoVax, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sanjeet S. Dadwal
Phone
626-218-8202
Email
sdadwal@coh.org
First Name & Middle Initial & Last Name & Degree
Sanjeet S. Dadwal
12. IPD Sharing Statement
Learn more about this trial
SARS-CoV-2 Vaccine (COH04S1) Versus EUA SARS-COV-2 Vaccine for the Treatment of COVID-19 in Patients With Blood Cancer
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