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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 : August 25, 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 escalation, non-randomized study of the safety, tolerability, and immunogenicity of investigational ChAd and SAM SARS-CoV-2 vaccines in healthy adult subjects. Homologous and heterologous prime-boost vaccination schedules (Stage 1), as well as boost(s) after receipt of COVID-19 Emergency Use Authorization (EUA) vaccines (Stage 2) will be examined. Subjects' willingness to receive ChAd vaccines will be assessed and documented at the time of informed consent and considered to determine group assignments. This phase 1 study will enroll 17 Stage 1 and up to 130 Stage 2 subjects. Eligible subjects will be enrolled in different groups based on their age (18-60 years old and >60 years old) and their COVID-19 EUA vaccination status. A sentinel approach with 72-hour observation times will be used in all groups, before recruiting the remainder of each dose escalation group. Decisions about dose escalation will be determined by the SSC after all subjects in each group have been observed through Day 8 post first study vaccination. All subjects will be followed through 12 months after their last study vaccination. Vaccinated subjects will be carefully monitored for exposure and infection to SARS-CoV-2 throughout the study. Before considering the use of 10 µg of SAM-S-TCE, safety, reactogenicity, and immunogenicity data through Day 15 after study vaccination from all lower dose group age-matched subjects (both 3 µg and 6 µg dose groups), as well as additional epidemiological data and literature will be evaluated to reassess the risk/benefit ratio for dose escalation. If intolerable reactogenicity as determined by the protocol team is seen in any 3 µg SAM-S-TCE group, but the immune data generated indicate immunogenicity of the spike and TCE antigens at this dosage, the protocol team may consider further dose de-escalation to 1 µg of SAM-S-TCE (Groups 16 and 17). In addition, the dosage of SAM-S-TCE given as a double boost to subjects previously vaccinated with Johnson & Johnson/Janssen Ad26 COVID-19 EUA vaccine in Groups 8 and 12 will be determined based on the dose escalation reactogenicity and immunogenicity results in Groups 5-7 and 9-11, respectively.

The primary objectives of this study are 1) 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-boost in healthy naïve adult subjects, 2) 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 boost in healthy adult subjects previously vaccinated with an mRNA or adenoviral-vectored COVID-19 EUA vaccine.


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 escalation, non-randomized study of the safety, tolerability, and immunogenicity of investigational ChAd and SAM SARS-CoV-2 vaccines in healthy adult subjects. Homologous and heterologous prime-boost vaccination schedules (Stage 1), as well as boost(s) after receipt of COVID-19 Emergency Use Authorization (EUA) vaccines (Stage 2) will be examined. Subjects' willingness to receive ChAd vaccines will be assessed and documented at the time of informed consent and considered to determine group assignments. This phase 1 study will enroll 17 Stage 1 and up to 130 Stage 2 subjects. Eligible subjects will be enrolled in different groups based on their age (18-60 years old and >60 years old) and their COVID-19 EUA vaccination status. A sentinel approach with 72-hour observation times will be used in all groups, before recruiting the remainder of each dose escalation group. Decisions about dose escalation will be determined by the SSC after all subjects in each group have been observed through Day 8 post first study vaccination. All subjects will be followed through 12 months after their last study vaccination. Vaccinated subjects will be carefully monitored for exposure and infection to SARS-CoV-2 throughout the study. Before considering the use of 10 µg of SAM-S-TCE, safety, reactogenicity, and immunogenicity data through Day 15 after study vaccination from all lower dose group age-matched subjects (both 3 µg and 6 µg dose groups), as well as additional epidemiological data and literature will be evaluated to reassess the risk/benefit ratio for dose escalation. If intolerable reactogenicity as determined by the protocol team is seen in any 3 µg SAM-S-TCE group, but the immune data generated indicate immunogenicity of the spike and TCE antigens at this dosage, the protocol team may consider further dose de-escalation to 1 µg of SAM-S-TCE (Groups 16 and 17). In addition, the dosage of SAM-S-TCE given as a double boost to subjects previously vaccinated with Johnson & Johnson/Janssen Ad26 COVID-19 EUA vaccine in Groups 8 and 12 will be determined based on the dose escalation reactogenicity and immunogenicity results in Groups 5-7 and 9-11, respectively.

The primary objectives of this study are 1) 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-boost in healthy naïve adult subjects, 2) 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 boost in healthy adult subjects previously vaccinated with an mRNA or adenoviral-vectored COVID-19 EUA vaccine. The secondary objective of this study is to assess the humoral immunogenicity of ChAd-S or ChAd-S-TCE, and SAM-S or SAM-S-TCE.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 147 participants
Allocation: Non-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 (Naïve) 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=4
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 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
Self-Amplifying mRNA - Lipid Nanoparticles - Spike (SAM-LNP-S) is a SAM vector based on Venezuelan Equine Encephalitis Virus (VEEV). A single 0.25 mL or 0.5 mL (depending on dose level) 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 (Naïve) Group 3A
30 mcg of SAM-LNP-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=3
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 0.25 mL or 0.5 mL (depending on dose level) 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 (Naïve) Group 3B
30 mcg SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 3 mcg of SAM-LNP-S administered through 0.25 mL intramuscular injection in the deltoid muscle on or after Day 85 and no later than Day 130 in participants from 18 to 60 years of age. N=7
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 0.25 mL or 0.5 mL (depending on dose level) 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 (Naïve) Group 4
10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on or after Day 85 and no later than Day 130 in participants from 18 to 60 years of age. N=3
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 0.25 or 0.5 mL (depending on dose level) 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 (ChAd-S-TCE Boosts after mRNA COVID-19 EUA Vaccines) Group 13
5 x 10^10 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and on or after 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 (depending on dose level) 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 (ChAd-S-TCE Boosts after mRNA COVID-19 EUA Vaccines) Group 14
1 x 10^11 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 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 (depending on dose level) 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 (ChAd-S-TCE Boosts after mRNA COVID-19 EUA Vaccines) Group 15
5 x 10^11 viral particles of ChAdV68-S-TCE administered through 1.0 mL intramuscular injection in the deltoid muscle on Day 1 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 (depending on dose level) 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 (SAM-S-TCE Boosts after Ad26 COVID-19 EUA Vaccinated) Group 8
10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 10 mcg of SAM-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: 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 0.25 or 0.5 mL (depending on dose level) 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 (SAM-S-TCE Boosts after Ad26 COVID-19 EUA Vaccines) Group 12
10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 10 mcg SAM-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: 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 0.25 or 0.5 mL (depending on dose level) 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 (SAM-S-TCE Boosts after mRNA COVID-19 EUA Vaccinated) Group 5
3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. 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 0.25 or 0.5 mL (depending on dose level) 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 (SAM-S-TCE Boosts after mRNA COVID-19 EUA Vaccinated) Group 6
6 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. 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 0.25 or 0.5 mL (depending on dose level) 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 (SAM-S-TCE Boosts after mRNA COVID-19 EUA Vaccinated) Group 7
10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. 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 0.25 or 0.5 mL (depending on dose level) 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 (SAM-S-TCE Boosts after mRNA COVID-19 EUA Vaccines) Group 10
6 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. 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 0.25 or 0.5 mL (depending on dose level) 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 (SAM-S-TCE Boosts after mRNA COVID-19 EUA Vaccines) Group 11
10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. 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 0.25 or 0.5 mL (depending on dose level) 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 (SAM-S-TCE Boosts after mRNA COVID-19 EUA Vaccines) Group 9
3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. 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 0.25 or 0.5 mL (depending on dose level) 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 Dose de-escalation (SAM-S TCE Boosts after mRNA COVID-19 EUA Vaccines) Group 16
1 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. 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 0.25 or 0.5 mL (depending on dose level) 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 Dose de-escalation (SAM-S TCE Boosts after mRNA COVID-19 EUA Vaccines) Group 17
1 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. 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 0.25 or 0.5 mL (depending on dose level) 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. Occurrence of Adverse Events of Special Interest (AESIs) [ Time Frame: Day 1 through Day 450 ]
    In naïve and previously vaccinated adults with mRNA or adenoviral-vectored COVID-19 EUA vaccine. Including potentially immune-mediated medical conditions (PIMMCs), medically attended adverse events (MAAEs), and new onset chronic medical conditions (NOCMCs)

  2. Occurrence of clinical safety laboratory adverse events by severity grade [ Time Frame: Through 7 days post each study vaccination ]
    In naïve and previously vaccinated adults with mRNA or adenoviral-vectored COVID-19 EUA vaccine. 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)

  3. Occurrence of Serious Adverse Events (SAEs) [ Time Frame: Day 1 through Day 450 ]
    In naïve and previously vaccinated adults with mRNA or adenoviral-vectored COVID-19 EUA vaccine.

  4. Occurrence of solicited local reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post each study vaccination ]
    In naïve and previously vaccinated adults with mRNA or adenoviral-vectored COVID-19 EUA vaccine.

  5. Occurrence of solicited systemic reactogenicity adverse events (AEs) [ Time Frame: Through 7 days post each study vaccination ]
    In naïve and previously vaccinated adults with mRNA or adenoviral-vectored COVID-19 EUA vaccine.

  6. Occurrence of unsolicited adverse events (AEs) [ Time Frame: Through 28 days post each study vaccination ]
    In naïve and previously vaccinated adults with mRNA or adenoviral-vectored COVID-19 EUA vaccine.


Secondary Outcome Measures :
  1. Geometric mean fold rise from baseline in titer measured by a SARS-CoV-2 neutralization assay [ Time Frame: Day 1 through Day 450 ]
    For wild-type virus and emergent viral strains

  2. Geometric mean fold rise from baseline in titer of receptor-binding domain (RBD) specific Immunoglobulin G (IgG) [ Time Frame: Day 1 through Day 450 ]
    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 450 ]
    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 [ Time Frame: Day 1 through Day 450 ]
    For wild-type virus and emergent viral strains

  5. Geometric mean titer of receptor-binding domain (RBD) specific Immunoglobulin G (IgG) [ Time Frame: Day 1 through Day 450 ]
    Covering spike and T cell epitope regions

  6. Geometric mean titer of Spike-specific Immunoglobulin G (IgG) [ Time Frame: Day 1 through Day 450 ]
    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 99 ]
    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 450 ]
    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 450 ]
    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 450 ]
    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 [ Time Frame: Day 1 through Day 450 ]
    Covering spike and T cell epitope regions, 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 99 ]
    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 450 ]
    Covering spike and T cell epitope regions

  14. Th1/Th2 cytokine balance of T cell response [ Time Frame: Through 28 days post boost vaccination ]
    Relative proportion of Th1 vs. Th2 type signature assessed 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 and categorizing as Th1 or Th2



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 men or non-pregnant women aged 18 years or older at enrollment
  4. Are in good health*

    *As defined by absence of clinically significant medical conditions defined by the CDC as increasing risk for severe corona virus disease-19 (COVID-19) (see exclusion criteria), or other acute or chronic medical conditions determined by medical history, physical examination (PE), 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). Any prescription change that is due to change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the participating site PI or appropriate sub- investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening of medical diagnosis/condition. Similarly, medication changes in the 60 days prior to enrollment as well as subsequent to enrollment and study vaccination are acceptable provided the change was not precipitated by deterioration in the chronic medical condition, and there is no anticipated additional risk to the subject or interference with the evaluation of responses to study vaccination.

  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:

    • Pulse > 50 and = / < 100 beats per minute
    • Systolic blood pressure (BP) = / < 140 millimeters of mercury (mmHg)
    • Diastolic BP = / < 90 mmHg
    • Oral temperature < 37.8 degrees Celsius (100.0 degrees Fahrenheit)
  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
  12. Received and completed COVID-19 vaccine under emergency use authorization (EUA) dosing guidelines at least 112 days prior to enrollment (Stage 2 only), as confirmed via CDC vaccination card or other appropriate documentation

A subject must meet all of the following criteria to be eligible for leukapheresis:

  1. Written informed consent for leukapheresis is provided
  2. Weight > / = 110 pounds
  3. Screening laboratory evaluations are within acceptable ranges at the site where the leukapheresis procedure will be performed
  4. Negative urine or serum pregnancy test at screening and on the day of the leukapheresis procedure for women of childbearing potential
  5. Adequate bilateral antecubital venous access
  6. No use of blood thinners, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs) at least 5 days before the leukapheresis procedure

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 anti-nucleoprotein severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody by enzyme-linked immunosorbent assay (ELISA) or by nasal swab polymerase chain reaction (PCR) at screening.
  3. Body mass index (BMI) > 30 kg/m^2 for Stage 1 participants and BMI > 35 kg/m^2 for Stage 2 participants.
  4. 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, diabetes mellitus, chronic liver disease, sickle cell disease

  5. Increased risk of occupational exposure to SARS-CoV-2 (healthcare workers and emergency response personnel)*

    *Applies to Stage 1 participants only

  6. Prior receipt of an investigational SARS-CoV-2 vaccine (including under EUA)*, approved or investigational adenovirus-vectored vaccines**, or any other approved or investigational vaccine likely to impact the interpretation of the trial data

    *Exclusion of prior receipt of COVID-19 EUA vaccines applies to Stage 1 participants only

    **With the exception of prior receipt of Johnson & Johnson/Janssen Ad 26 COVID-19 EUA vaccine which is permitted for Groups 8 and 12

  7. On current treatment or prevention agents with activity against SARS-CoV-2
  8. Current smoking or vaping or history of smoking or vaping in prior year*

    *Applies to Stage 1 participants only

  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 human immunodeficiency virus (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 or family history of bleeding disorder
  23. Recent (within the past 3 months) surgery, immobility, chronic infection, or head trauma that could increase the risks of thrombosis.
  24. Suspected or known current alcohol abuse. Suspected or known drug abuse in the 5 years preceding enrollment
  25. Seropositive for HIV, hepatitis B surface antigen (HBsAg), or seropositive for hepatitis C virus (antibodies to HCV)
  26. 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

  27. History of venous or arterial thrombosis or any known thrombophilic condition including heparin-induced thrombocytopenia (HIT) or family history of thrombosis.
  28. History of Guillain-Barre Syndrome (GBS).
  29. Receiving heparin treatment or on medications associated with increased risk of bleeding or thrombosis.
  30. 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 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: August 25, 2021
Last Verified: August 17, 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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COVID-19
Adenoviridae Infections
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
DNA Virus Infections