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Chimpanzee Adenovirus and Self-Amplifying mRNA Prime-Boost Prophylactic Vaccines Against SARS-CoV-2 in Healthy Adults

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ClinicalTrials.gov Identifier: NCT04776317
Recruitment Status : Recruiting
First Posted : March 1, 2021
Last Update Posted : April 20, 2021
Sponsor:
Collaborator:
Gritstone Oncology, Inc.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a multicenter, US-only, phase 1, open-label, dose and age escalation, parallel design (heterologous and homologous prime-boost) study to examine safety, tolerability, and immunogenicity of investigational Chimpanzee Adenovirus serotype 68 (ChAd) and self-amplifying mRNA (SAM) vectors expressing either Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike alone, or spike plus additional SARS-CoV-2 T cell epitopes (TCE) in healthy adult subjects. Stage 1 will compare ChAd and SAM vaccines encoding only the spike protein in a 2-group dose escalation trial in subjects 18-60 years old, and a 3-group dose escalation trial in subjects over 60 years old, focusing on heterologous ChAd prime/SAM boost and homologous SAM prime/SAM boost regimens including sentinels, and staggered enrollment for dose and age escalations. Stage 2 will compare optimal doses of ChAd and SAM vaccines (determined in Stage 1) encoding both spike and TCE, in subjects 18 years and older enrolled into up to 6 groups simultaneously to receive homologous SAM prime/SAM boost, homologous ChAd prime/ChAd boost and heterologous ChAd prime/SAM boost combinations. Up to 70 (Stage 1) and up to 70 (Stage 2) males and non-pregnant females >/= 18 years of age who are in good health, do not have high risks for SARS-CoV-2 infection or for severe Coronavirus Disease 2019 (COVID-19) disease progression, and meet all eligibility criteria will be enrolled. Subjects will be enrolled at one of at least 3 distinct US-based Infectious Diseases Clinical Research Consortium (IDCRC) sites into different groups based on their age (18-60 and >60 years old). The primary objective of this study is to assess the safety and tolerability of different doses of ChAd-S (or ChAd-S-TCE) and SAM-S (or SAM-S-TCE) when administered as prime and/or boost in healthy adult subjects including older adult subjects.

Condition or disease Intervention/treatment Phase
COVID-19 Biological: ChAdV68-S Biological: ChAdV68-S-TCE Biological: SAM-LNP-S Biological: SAM-LNP-S-TCE Other: Sodium Chloride, 0.9% Phase 1

Detailed Description:
This is a multicenter, US-only, phase 1, open-label, dose and age escalation, parallel design (heterologous and homologous prime-boost) study to examine safety, tolerability, and immunogenicity of investigational Chimpanzee Adenovirus serotype 68 (ChAd) and self-amplifying mRNA (SAM) vectors expressing either Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike alone, or spike plus additional SARS-CoV-2 T cell epitopes (TCE) in healthy adult subjects. Stage 1 will compare ChAd and SAM vaccines encoding only the spike protein in a 2-group dose escalation trial in subjects 18-60 years old, and a 3-group dose escalation trial in subjects over 60 years old, focusing on heterologous ChAd prime/SAM boost and homologous SAM prime/SAM boost regimens including sentinels, and staggered enrollment for dose and age escalations. Stage 2 will compare optimal doses of ChAd and SAM vaccines (determined in Stage 1) encoding both spike and TCE, in subjects 18 years and older enrolled into up to 6 groups simultaneously to receive homologous SAM prime/SAM boost, homologous ChAd prime/ChAd boost and heterologous ChAd prime/SAM boost combinations. Up to 70 (Stage 1) and up to 70 (Stage 2) males and non-pregnant females >/= 18 years of age who are in good health, do not have high risks for SARS-CoV-2 infection or for severe Coronavirus Disease 2019 (COVID-19) disease progression, and meet all eligibility criteria will be enrolled. Subjects will be enrolled at one of at least 3 distinct US-based Infectious Diseases Clinical Research Consortium (IDCRC) sites into different groups based on their age (18-60 and >60 years old). The primary objective of this study is to assess the safety and tolerability of different doses of ChAd-S (or ChAd-S-TCE) and SAM-S (or SAM-S-TCE) when administered as prime and/or boost in healthy adult subjects including older adult subjects. The secondary objective of this study is to assess the humoral and T cell responses to ChAd-S (or ChAd-S-TCE) and SAM-S (or SAM-S-TCE) when administered to healthy adult subjects including older adult subjects.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 1 Trial to Evaluate the Safety, Immunogenicity, and Reactogenicity of Heterologous and Homologous Chimpanzee Adenovirus and Self-Amplifying mRNA Prime-Boost Prophylactic Vaccines Against SARS-CoV-2 in Healthy Adults
Actual Study Start Date : March 25, 2021
Estimated Primary Completion Date : September 19, 2022
Estimated Study Completion Date : September 19, 2022

Arm Intervention/treatment
Experimental: Stage 1 Group 1
5 x 10^10 viral particles of ChAdV68-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants from 18 to 60 years of age. N=10
Biological: ChAdV68-S
Chimpanzee Adenovirus serotype 68 - Spike (ChAdV68-S) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5 mL or 1.0 mL intramuscular injection (depending on dose level) will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Biological: SAM-LNP-S
Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 1 Group 2
1 x 10^11 viral particles of ChAdV68-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants from 18 to 60 years of age. N=10
Biological: ChAdV68-S
Chimpanzee Adenovirus serotype 68 - Spike (ChAdV68-S) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5 mL or 1.0 mL intramuscular injection (depending on dose level) will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Biological: SAM-LNP-S
Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 1 Group 3
30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and Day 29 in participants from 18 to 60 years of age. N=10
Biological: SAM-LNP-S
Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 1 Group 4
100 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and Day 29 in participants from 18 to 60 years of age. N=10
Biological: SAM-LNP-S
Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 1 Group 5
5 x 10^10 viral particles of ChAdV68-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants older than 60 years of age. N=10
Biological: ChAdV68-S
Chimpanzee Adenovirus serotype 68 - Spike (ChAdV68-S) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5 mL or 1.0 mL intramuscular injection (depending on dose level) will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Biological: SAM-LNP-S
Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 1 Group 6
1 x 10^11 viral particles of ChAdV68-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants older than 60 years of age. N=10
Biological: ChAdV68-S
Chimpanzee Adenovirus serotype 68 - Spike (ChAdV68-S) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5 mL or 1.0 mL intramuscular injection (depending on dose level) will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Biological: SAM-LNP-S
Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 1 Group 7
5 x 10^11 viral particles of ChAdV68-S administered through 1.0 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants older than 60 years of age. N=10
Biological: ChAdV68-S
Chimpanzee Adenovirus serotype 68 - Spike (ChAdV68-S) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5 mL or 1.0 mL intramuscular injection (depending on dose level) will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Biological: SAM-LNP-S
Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 2 Group 10
1 x 10^11 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and Day 113 in participants from 18 to 60 years of age. N=10
Biological: ChAdV68-S-TCE
Chimpanzee Adenovirus 68 - Spike plus additional SARS-CoV-2 T cell epitopes (ChAdV68-S-TCE) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5- or 1.0-mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 2 Group 11
1 x 10^11 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and Day 113 OR 5 x 10^11 viral particles of ChAdV68-S-TCE administered through 1.0 mL intramuscular injection in the deltoid muscle on Day 1 and Day 113 in participants older than 60 years of age. N=10
Biological: ChAdV68-S-TCE
Chimpanzee Adenovirus 68 - Spike plus additional SARS-CoV-2 T cell epitopes (ChAdV68-S-TCE) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5- or 1.0-mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 2 Group 12
10 mcg of SAM-LNP-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 years of age or older. N=10.
Biological: SAM-LNP-S-TCE
Self-Amplifying mRNA - Lipid Nanoparticles -Spike plus additional SARS-CoV-2 T cell epitopes (SAM-S-TCE) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 2 Group 13
30 mcg of SAM-LNP-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 years of age and older. N=10
Biological: SAM-LNP-S-TCE
Self-Amplifying mRNA - Lipid Nanoparticles -Spike plus additional SARS-CoV-2 T cell epitopes (SAM-S-TCE) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 2 Group 14
100 mcg of SAM-LNP-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 years of age and older. N=10
Biological: SAM-LNP-S-TCE
Self-Amplifying mRNA - Lipid Nanoparticles -Spike plus additional SARS-CoV-2 T cell epitopes (SAM-S-TCE) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 2 Group 8
5 x 10^10 viral particles of ChAdV68-S-TCE OR 1 x 10^11 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 57 in participants from 18 to 60 years of age. N=10
Biological: ChAdV68-S-TCE
Chimpanzee Adenovirus 68 - Spike plus additional SARS-CoV-2 T cell epitopes (ChAdV68-S-TCE) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5- or 1.0-mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Biological: SAM-LNP-S-TCE
Self-Amplifying mRNA - Lipid Nanoparticles -Spike plus additional SARS-CoV-2 T cell epitopes (SAM-S-TCE) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.

Experimental: Stage 2 Group 9
5 x 10^10 viral particles of ChAdV68-S-TCE OR 1 x 10^11 viral particles of ChAdV68-S-TCE OR 5 x 10^11 viral particles of ChAdV68-S-TCE administered through 0.5 mL or 1.0 mL (for 5 x 10^11 viral particles) intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 57 in participants older than 60 years of age. N=10
Biological: ChAdV68-S-TCE
Chimpanzee Adenovirus 68 - Spike plus additional SARS-CoV-2 T cell epitopes (ChAdV68-S-TCE) is a replication-defective, E1, E3 E4Orf2-4 deleted adenoviral vector based on chimpanzee adenovirus 68 (C68, 68/SAdV-25, originally designated as Pan 9), which belongs to the sub-group E adenovirus family. A single 0.5- or 1.0-mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Biological: SAM-LNP-S-TCE
Self-Amplifying mRNA - Lipid Nanoparticles -Spike plus additional SARS-CoV-2 T cell epitopes (SAM-S-TCE) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.

Other: Sodium Chloride, 0.9%
The diluent used for this study will be 0.9% Sodium Chloride Injection, USP, and is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each milliliter (mL) contains sodium chloride 9 mg. It contains no bacteriostat, antimicrobial agent or added buffer and is supplied only in single-dose containers to dilute or dissolve drugs for injection. 0.308 mOsmol/mL (calc.). 0.9% Sodium Chloride Injection, USP contains no preservatives.




Primary Outcome Measures :
  1. Frequency by grade of solicited local reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post each vaccination ]
  2. Frequency by grade of solicited systemic reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post each vaccination ]
  3. Frequency by grade of unsolicited adverse events (AEs) [ Time Frame: Through 28 days post each vaccination ]
  4. Frequency of Adverse Events of Special Interest (AESIs) [ Time Frame: Day 1 through Day 478 ]
    Including potentially immune-mediated medical conditions (PIMMCs), medically attended adverse events (MAAEs), and new onset chronic medical conditions (NOCMCs)

  5. Frequency of clinical safety laboratory adverse events by severity grade [ Time Frame: Through 7 days post each vaccination ]
    Parameters to be evaluated include: white blood cell count (WBC), hemoglobin (HgB), platelets (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (T Bili), creatine kinase (CK), and creatinine (Cr)

  6. Frequency of Serious Adverse Events (SAEs) [ Time Frame: Day 1 through Day 478 ]

Secondary Outcome Measures :
  1. Geometric mean fold rise from baseline in titer measured by a SARS-CoV-2 neutralization assay, for wild-type virus and emergent viral strains [ Time Frame: Day 1 through Day 478 ]
  2. Geometric mean fold rise from baseline in titer of receptor-binding domain (RBD) specific Immunoglobulin G (IgG) [ Time Frame: Day 1 through Day 478 ]
    Measured by an Enzyme-Linked Immunosorbent Assay (ELISA), for RBD from wild-type virus and emergent viral strains

  3. Geometric mean fold rise from baseline in titer of Spike-specific Immunoglobulin G (IgG) [ Time Frame: Day 1 through Day 478 ]
    Measured by an Enzyme-Linked Immunosorbent Assay (ELISA), for spike protein from wild-type virus and emergent viral strains

  4. Geometric mean titer measured by a SARS-CoV-2 neutralization assay, for wild-type virus and emergent viral strains [ Time Frame: Day 1 through Day 478 ]
  5. Geometric mean titer of receptor-binding domain (RBD) specific Immunoglobulin G (IgG) [ Time Frame: Day 1 through Day 478 ]
    Measured by an Enzyme-Linked Immunosorbent Assay (ELISA), for RBD from wild-type virus and emergent viral strains

  6. Geometric mean titer of Spike-specific Immunoglobulin G (IgG) [ Time Frame: Day 1 through Day 478 ]
    Measured by an Enzyme-Linked Immunosorbent Assay (ELISA), for spike protein from wild-type virus and emergent viral strains

  7. Percent of cells expressing a cytokine by cell type (CD4+ or CD8+), cytokine set (Th1 or Th2 cytokine for CD4+ and CD8+ cytokine for CD8+ or other combinations of interest) and peptide pool (covering spike and T cell epitope regions) [ Time Frame: Day 1 through Day 478 ]
    As determined by ICS

  8. Percentage of subjects who seroconverted, for RBD from wild-type virus and emergent viral strains [ Time Frame: Day 1 through Day 478 ]
    Seroconversion defined as a 4-fold change in receptor-binding domain (RBD) specific IgG from baseline measured by ELISA. Including against emergent viral strains, e.g., B.1.1.7. Assessed by a range of assays measuring total Spike-specific Immunoglobulin G (IgG) (Enzyme-Linked Immunosorbent Assay (ELISA)-based) and function (neutralization, receptor-binding domain (RBD) binding, or similar) in serum

  9. Percentage of subjects who seroconverted, for spike protein from wild-type virus and emergent viral strains [ Time Frame: Day 1 through Day 478 ]
    Seroconversion defined as a 4-fold change in Spike-specific Immunoglobulin G (IgG) from baseline measured by an Enzyme-Linked Immunosorbent Assay (ELISA). Including against emergent viral strains, e.g., B.1.1.7. Assessed by a range of assays measuring total Spike-specific Immunoglobulin G (IgG) (Enzyme-Linked Immunosorbent Assay (ELISA)-based) and function (neutralization, receptor-binding domain (RBD) binding, or similar) in serum

  10. Percentage of subjects who seroconverted, for wild-type virus and emergent viral strains [ Time Frame: Day 1 through Day 478 ]
    Seroconversion defined as a 4-fold change in titer from baseline measured by a SARS-CoV-2 neutralization assay. Including against emergent viral strains, e.g., B.1.1.7. Assessed by a range of assays measuring total Spike-specific Immunoglobulin G (IgG) (Enzyme-Linked Immunosorbent Assay (ELISA)-based) and function (neutralization, receptor-binding domain (RBD) binding, or similar) in serum

  11. Rate of spot-forming cell per million cells by peptide pool (covering spike and T cell epitope regions) [ Time Frame: Day 1 through Day 478 ]
    As determined by interferon (IFN) gamma Enzyme Linked Immunospot Assay (ELISpot)

  12. Responder status, derived from the intracellular cytokine staining (ICS) cell counts for each set of applicable cytokines and each peptide pool [ Time Frame: Day 1 through Day 478 ]
    Covering spike and T cell epitope regions

  13. Responder status, determined by interferon (IFN) gamma Enzyme Linked Immunospot Assay (ELISpot) for each peptide pool [ Time Frame: Day 1 through Day 478 ]
    Covering spike and T cell epitope regions

  14. Th1/Th2 cytokine balance of T cell response [ Time Frame: Through 28 days post boost vaccination ]
    By measuring interleukin (IL) 2, tumor necrosis factor (TNF) alpha, IL-4, IL-10, and IL-13 using a multiplexed cytokine assay with Enzyme Linked Immunospot Assay (ELISpot) supernatants in a subset of subjects



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects eligible to participate in this trial must meet all of the following inclusion criteria:

  1. Provide written informed consent prior to initiation of any study procedures
  2. Able and willing (in the investigator's opinion) to comply with all study requirements
  3. Are males or non-pregnant females aged 18 years or older at enrollment
  4. Are in good health*

    *As defined by absence of clinically significant medical conditions defined by The Centers for Disease Control and Prevention (CDC) as increasing risk for severe coronavirus disease 2019 (COVID-19) disease (see exclusion criteria), or other acute or chronic medical conditions determined by medical history, physical examination, screening laboratory test results, and/or clinical assessment of the investigator that are either listed as exclusion criteria below or in the opinion of the investigator would increase risk for study participation or affect the assessment of the safety of subjects. Chronic medical conditions should be stable for the last 60 days (no hospitalizations, emergency room or urgent care for condition, or invasive medical procedures). This includes no change in chronic prescription medications in the 60 days prior to enrollment

  5. Agree to refrain from blood donation during the course of the study
  6. Plan to remain living in the area for the duration of the study
  7. Women of childbearing potential (WOCBP)* must plan to avoid pregnancy for at least 60 days after the last study vaccination and be willing to use an adequate method of contraception** consistently for 30 days prior to first study vaccine and for at least 60 days after the last study vaccine.

    *Not sterilized via bilateral oophorectomy, tubal ligation/salpingectomy, hysterectomy, or successful Essure (R) placement (permanent, non-surgical, non-hormonal sterilization with documented radiological confirmation test at least 90 days after the procedure); still menstruating; or < 1 year has passed since the last menses if menopausal

    **Acceptable methods of birth control include the following: oral contraceptives, injection hormonal contraceptive, implant hormonal contraceptive, hormonal patch, intrauterine device, spermicidal products and barrier methods (such as cervical sponge, diaphragm, or condom with spermicide), abstinence, monogamous with a vasectomized partner, non-male sexual relationship

  8. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each study vaccination
  9. Vital signs within acceptable ranges:

    • Heart rate > 50 and < 100 beats per minute
    • Systolic blood pressure = / < 140 millimeters of mercury (mmHg)
    • Diastolic blood pressure = / < 90 mmHg
    • Temperature < 37.8°C (100.0°F)
  10. Clinical screening lab evaluations (white blood cell (WBC), hemoglobin (HgB), platelets (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (T Bili), creatine kinase, (CK), serum creatinine (Cr) and prothrombin time (PT)/partial thromboplastin time (PTT)) are within acceptable normal reference ranges at the clinical lab being used, with the exception that ALT, AST, ALP, and creatinine values that are below the reference range will not be exclusionary as these values below reference range are clinically insignificant. Any other screening lab value outside the reference range that is thought to be clinically insignificant by a site investigator must be discussed with the DMID Medical Officer prior to enrollment
  11. Must agree to genetic testing and storage of samples for secondary research

Exclusion Criteria:

Subjects eligible to participate in this trial must not meet any of the following exclusion criteria:

  1. History of prior confirmed coronavirus disease 2019 (COVID-19)
  2. Positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by enzyme-linked immunosorbent assay (ELISA) or by nasal swab polymerase chain reaction (PCR) at screening.
  3. Presence of medical comorbidities that would place the subject at increased risk for severe COVID-19*

    *chronic kidney disease, chronic lung disease (including moderate-to-severe asthma), chronic heart disease (heart failure, coronary artery disease or cardiomyopathies), cerebrovascular disease, body mass index(BMI) > / = 30 kg/m2, diabetes mellitus, chronic liver disease, sickle cell disease

  4. Increased risk of occupational exposure to SARS-CoV-2 (healthcare workers and emergency response personnel)
  5. Prior receipt of an investigational SARS-CoV-2 vaccine (including under emergency use authorization [EUA]), approved or investigational adenovirus vectored vaccines, approved or investigational vaccines with an LNP component, or any other approved or investigational vaccine likely to impact the interpretation of the trial data
  6. On current treatment or prevention agents with activity against SARS-CoV-2
  7. Current smoking or vaping
  8. History of smoking or vaping in prior year
  9. Breastfeeding, pregnant, or planning to become pregnant during the course of the study.
  10. Participation in another research study involving receipt of an investigational product in the 60 days preceding enrolment or planned use during the study period
  11. Receipt or planned receipt of any live, attenuated vaccine within 28 days before or after study vaccination
  12. Receipt or planned receipt of any subunit or killed vaccine within 14 days before or after vaccination
  13. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of first study vaccination or at any time during the study
  14. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia, recurrent, severe infections and chronic (more than 14 continuous days) immunosuppressant medication within the past 6 months (inhaled, ophthalmic and topical steroids are allowed)
  15. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including urticaria, respiratory difficulty or abdominal pain (or any immediate allergic reaction of any severity to polysorbate due to potential cross-reactive hypersensitivity with the polyethylene glycol component of the vaccine)
  16. Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema
  17. Any history of anaphylaxis, including but not limited to reaction to vaccination
  18. Any history of severe allergic drug reaction
  19. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
  20. History of serious ongoing, unstable psychiatric condition that in the opinion of the investigator would interfere with study participation
  21. Seizure in the past 3 years or treatment for seizure disorder in the past 3 years
  22. Bleeding disorder (e.g., Factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture
  23. Suspected or known current alcohol abuse. Suspected or known drug abuse in the 5 years preceding enrollment
  24. Seropositive for HIV, hepatitis B surface antigen (HBsAg) or seropositive for hepatitis C virus (antibodies to HCV)
  25. Have an acute illness* within 72 hours prior to study vaccination

    *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol

  26. Any other condition that in the opinion of the investigator would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04776317


Contacts
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Contact: Daniel F. Hoft 13149775500 daniel.hoft@health.slu.edu

Locations
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United States, Georgia
Emory Vaccine Center - The Hope Clinic Recruiting
Decatur, Georgia, United States, 30030-1705
United States, Missouri
Saint Louis University - Center for Vaccine Development Recruiting
Saint Louis, Missouri, United States, 63104-1015
United States, Texas
Baylor College of Medicine - Molecular Virology and Microbiology Not yet recruiting
Houston, Texas, United States, 77030-3411
United States, Washington
The University of Washington - Virology Research Clinic Recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Gritstone Oncology, Inc.
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04776317    
Other Study ID Numbers: 20-0034
5UM1AI148684-02 ( U.S. NIH Grant/Contract )
First Posted: March 1, 2021    Key Record Dates
Last Update Posted: April 20, 2021
Last Verified: April 9, 2021

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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
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Immunogenicity
Prime-Boost
Reactogenicity
Safety
SARS-CoV-2
vaccine
Additional relevant MeSH terms:
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Adenoviridae Infections
DNA Virus Infections
Virus Diseases