Purpose

This is a multicenter, US-only, phase 1, open-label, dose escalation, non-randomized study of the 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. Homologous and heterologous prime-boost vaccination schedules (Stage 1), as well as boost(s) after receipt of COVID-19 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 I will enroll 50 (Stage 1) and 90 (Stage 2) subjects. 10 additional subjects, and up to 150 more may be enrolled as necessary. Eligible subjects will be enrolled in different groups based on their age (18-60 years and >60 years and their COVID-19 EUA vaccination status. A sentinel approach with 72-hour observation times will be used in 1all groups, except Group 14, 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 vaccine study. Group 1A subjects will be combined with the first six Group 1B subjects for assessment of dose escalation criteria prior to Group 2. All subjects will be followed through 12 months after the their last vaccination. Vaccinated subjects will be carefully monitored for exposure and infection to SARS-CoV-2 throughout the study. 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

Eligibility

Eligible Ages
Between 18 Years and 60 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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 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, 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: - Heart rate > 50 and = / < 100 beats per minute - Systolic blood pressure = / < 140 millimeters of mercury (mmHg) - Diastolic blood pressure = / < 90 mmHg - 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 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 emergency use authorization [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 and Johnson/Janssen SARS-CoV-2 EUA vaccine which is permitted for Group 14 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 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. History of venous or arterial thrombosis or any known thrombophilic condition including heparin-induced thrombocytopenia (HIT). 27. 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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Stage 1 (Naïve) Group 1A
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 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 (Naïve) Group 1B
5 x 10^10 viral particles of ChAdV68-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 10 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 57 in participants from 18 to 60 years of age. N=6-10
  • 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 (Naïve) 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 10 mcg of SAM-LNP-S 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
    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 (Naïve) Group 3A
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=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 0.5 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 (Naïve) Group 3B
30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 10 mcg on a Day 57 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 0.5 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 (Naïve) Group 4
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 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 0.5 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 (Naïve) Group 5
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 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 0.5 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 (Adenoviral-vectored COVID-19 EUA Vaccinated) Group 14
10 mcg of SAM-LNP-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1, Day 57 and on or after Day 113 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 0.5 mL intramuscular injection will be administered in the deltoid muscle. When possible, the prime vaccine and boost vaccine should be administered in different arms.
Experimental
Stage 2 (mRNA COVID-19 EUA Vaccinated) Group 10
30 mcg of SAM-LNP-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: 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 (mRNA COVID-19 EUA Vaccinated) Group 11
100 mcg of SAM-LNP-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: 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 (mRNA COVID-19 EUA Vaccinated) Group 12
10 mcg of SAM-LNP-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and on or after Day 113 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 0.5 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 (mRNA COVID-19 EUA Vaccinated) Group 13
30 mcg of SAM-LNP-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and on or after Day 113 in participants 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 0.5 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 (mRNA COVID-19 EUA Vaccinated) Group 6
5 x 10^10 viral particles of ChAdV68-S-TCE administered through 1.0 mL intramuscular injection in the deltoid muscle on Day 1 and on or after day 113 in participants older than60 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 (mRNA COVID-19 EUA Vaccinated) Group 7
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 on or after Day 113 in participants from 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 (mRNA COVID-19 EUA Vaccinated) Group 8
5 x 10^11 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 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 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 (mRNA COVID-19 EUA Vaccinated) Group 9
10 mcg of SAM-LNP-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: 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.

Recruiting Locations

Emory Vaccine Center - The Hope Clinic
Decatur, Georgia 30030-1705

Saint Louis University - Center for Vaccine Development
Saint Louis, Missouri 63104-1015

Baylor College of Medicine - Molecular Virology and Microbiology
Houston, Texas 77030-3411

The University of Washington - Virology Research Clinic
Seattle, Washington 98104

More Details

NCT ID
NCT04776317
Status
Recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact

Daniel F. Hoft
13149775500
daniel.hoft@health.slu.edu

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 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. Homologous and heterologous prime-boost vaccination schedules (Stage 1), as well as boost(s) after receipt of COVID-19 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 I will enroll 50 (Stage 1) and 90 (Stage 2) subjects. 10 additional subjects, and up to 150 more may be enrolled as necessary. Eligible subjects will be enrolled in different groups based on their age (18-60 years and >60 years and their COVID-19 EUA vaccination status. A sentinel approach with 72-hour observation times will be used in 1all groups, except Group 14, 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 vaccine study. Group 1A subjects will be combined with the first six Group 1B subjects for assessment of dose escalation criteria prior to Group 2. All subjects will be followed through 12 months after the their last vaccination. Vaccinated subjects will be carefully monitored for exposure and infection to SARS-CoV-2 throughout the study. 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 and T cell responses to ChAd-S (or ChAd-S-TCE) and SAM-S (or SAM-S-TCE)

Notice

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