Chimpanzee Adenovirus and Self-Amplifying mRNA Prime-Boost Prophylactic Vaccines Against SARS-CoV-2 in Healthy Adults
Condition: COVID-19
MeSH terms: Adenoviridae Infections
Study type: Interventional
Phase: Phase 1

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.
    

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 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. 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.
    

Intervention name(s): ChAdV68-S; ChAdV68-S-TCE; SAM-LNP-S; SAM-LNP-S-TCE; Sodium Chloride, 0.9%
Intervention type(s): Biological; Biological; Biological; Biological; Other
Intervention description(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.; 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.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Immunogenicity; Prime-Boost; Reactogenicity; Safety; SARS-CoV-2; vaccine