Chimpanzee Adenovirus and Self-Amplifying mRNA Prime-Boost Prophylactic Vaccines Against SARS-CoV-2 in Healthy Adults
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
2 other identifiers
interventional
81
1 country
4
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 EUA/licensed 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 118 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 EUA/licensed COVID-19 vaccination status. A sentinel approach with 72-hour (Stage 1, and Stage 2, Groups 5, 6, 8-10, 12, 13-15) or 7-day observation times (Groups 7 and 11) will be used, before recruiting the remainder of each dose escalation group. Decisions about dose escalation will be determined by the SSC with consultation with the DSMB as needed 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. Escalation to the highest dose (10 µg) of SAM-S-TCE in younger subjects will proceed only following safety assessments of the 10 µg dose in older subjects for a period of 28 days post-vaccination. In addition, the dosage of SAM-S-TCE given as a double boost to subjects previously vaccinated with the Johnson \& Johnson/Janssen Ad26 COVID-19 EUA/licensed vaccine in Groups 8A, 8B, and 12A, 12B will be determined based on the dose escalation reactogenicity and immunogenicity results in Groups 5-7 and 9-11, respectively. After protocol version 9.0 was implemented, it was decided not to enroll subjects into Groups 7 and 8 because of competing priorities and predicted difficulties enrolling into these two groups. 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 first or second boost in healthy adult subjects previously vaccinated with an mRNA or adenoviral-vectored COVID-19 EUA/licensed vaccine.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 covid19
Started Mar 2021
Longer than P75 for phase_1 covid19
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 25, 2021
CompletedFirst Posted
Study publicly available on registry
March 1, 2021
CompletedStudy Start
First participant enrolled
March 25, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 15, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
September 15, 2023
CompletedResults Posted
Study results publicly available
January 31, 2025
CompletedMay 16, 2025
April 20, 2022
2.5 years
February 25, 2021
September 5, 2024
May 8, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
Frequency of Any New-onset Chronic Medical Conditions (NOCMCs)
Number of participants that experienced any NOCMCs during the course of the study
Day 1 to study completion through up to 1 year post last dose
Frequency of Any Potentially Immune-mediated Medical Conditions (PIMMCs)
Number of participants that experienced any PIMMCs during the course of the study
Day 1 to study completion through up to 1 year post last dose
Frequency of Any Medically Attended Adverse Events (MAAEs)
Number of participants that experienced any MAAEs during the course of the study
Day 1 to study completion through up to 1 year post last dose
Frequency of Any Laboratory AE
Number of participants that experienced any laboratory AE
Through 7 days post each study vaccination
Frequency of Any Serious Adverse Events (SAEs)
The number of participants that experience any SAEs from Day 1 to study completion. An AE or suspected adverse reaction is considered serious if, in the view of either the participating site PI or appropriate sub-investigator or the sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Day 1 to study completion through up to 1 year post last dose
Frequency of Systemic Solicited Reactogenicity Adverse Events (AEs)
Number of participants who experienced any systemic solicited AEs through 7 days post any vaccination. Systemic events include: fatigue, headache, myalgia, arthralgia, nausea, chills and fever.
Day 1 through Day 8 for Groups 5, 6, 9, 10, 11, 13, 14 and 15 and through 7 days post any vaccination for Groups 1, 3A, 3b and 4.
Frequency of Local Solicited Reactogenicity Adverse Events (AEs)
Number of participants who experienced any local solicited AEs through 7 days post any vaccination. Local events include: pain at injection site, erythema, and induration.
Day 1 through Day 8 for Groups 5, 6, 9, 10, 11, 13, 14 and 15 and through 7 days post any vaccination for Groups 1, 3A, 3b and 4.
Frequency of Any Unsolicited Adverse Events (AEs)
Number of participants who experienced any unsolicited AEs through 28 days post vaccination
Day 1 through Day 29 for Groups 5, 6, 9, 10, 11, 13, 14 and 15 and 28 days post any vaccination for Groups 1, 3A, 3b and 4.
Secondary Outcomes (130)
Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against D614G for Groups 1 and 3A
Day 29 Post Vaccination 1, Day 57 Post Vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)
Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.1 for Groups 1 and 3A
Day 57 Post Vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)
Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.4/5 for Groups 1 and 3A
Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)
Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against D614G for Groups 3B and 4
Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1
Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.1 for Groups 3B and 4
Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1
- +125 more secondary outcomes
Study Arms (15)
Stage 1 (Naïve) Group 1
EXPERIMENTAL5 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
Stage 1 (Naïve) Group 3A
EXPERIMENTAL30 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
Stage 1 (Naïve) Group 3B
EXPERIMENTAL30 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
Stage 1 (Naïve) Group 4
EXPERIMENTAL10 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
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 13
EXPERIMENTAL5 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=7-10
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 14
EXPERIMENTAL1 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=7-10
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 15
EXPERIMENTAL5 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=7-10
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 10A,B
EXPERIMENTAL6 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=8-12
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 11A,B
EXPERIMENTAL10 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=8-12
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 12A,B
EXPERIMENTAL10 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=8-12
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 9
EXPERIMENTAL3 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=8
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 5
EXPERIMENTAL3 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
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 6
EXPERIMENTAL6 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
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 7A,B
EXPERIMENTAL10 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=8-12
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 8A,B
EXPERIMENTAL10 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=8-12
Interventions
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.
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- Provide written informed consent prior to initiation of any study procedures
- Able and willing (in the investigator's opinion) to comply with all study requirements
- Are men or non-pregnant women aged 18 years or older at enrollment
- Are in good health\*
You may not qualify if:
- Agree to refrain from blood donation during the course of the study
- Plan to remain living in the area for the duration of the study
- 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
- Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each study vaccination
- 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)
- Must agree to genetic testing and storage of samples for secondary research
- Received at least 2 doses of EUA/licensed mRNA vaccines or at least 1 dose of Ad26 vaccine followed by an mRNA booster, with the last COVID-19 vaccine dose given at least 112 days prior to enrollment (Stage 2 only), as confirmed via CDC vaccination card or other appropriate documentation. Subjects may or may not have been previously infected with SARS-CoV-2.
- A subject must meet all of the following criteria to be eligible for leukapheresis:
- Written informed consent for leukapheresis is provided
- +42 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
The Hope Clinic of Emory University
Decatur, Georgia, 30030-1705, United States
Saint Louis University Center for Vaccine Development
St Louis, Missouri, 63104-1015, United States
Baylor College of Medicine
Houston, Texas, 77030-3411, United States
The University of Washington - Virology Research Clinic
Seattle, Washington, 98104, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Daniel F. Hoft, MD, PhD
- Organization
- Saint Louis University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 25, 2021
First Posted
March 1, 2021
Study Start
March 25, 2021
Primary Completion
September 15, 2023
Study Completion
September 15, 2023
Last Updated
May 16, 2025
Results First Posted
January 31, 2025
Record last verified: 2022-04-20