Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines
Condition: COVID-19
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      A phase 1/2, open-label clinical trial in individuals, 18 years of age and older, who are in
      good health, have no known history of Coronavirus Disease 2019 (COVID-19) or Severe Acute
      Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and meet all other eligibility
      criteria. This clinical trial is designed to assess the safety, reactogenicity and
      immunogenicity of a delayed (>/=12 weeks) vaccine boost on a range of Emergency Use
      Authorization (EUA)-dosed COVID-19 vaccines (mRNA-1273, and mRNA-1273.211 manufactured by
      ModernaTX, Inc.; BNT162b2 manufactured by Pfizer/BioNTech; or Ad26.COV2.S manufactured by
      Janssen Pharmaceuticals/Johnson & Johnson). This is an adaptive design and may add arms (and
      increase sample size) as vaccines are awarded EUA and/or variant lineage spike vaccines are
      manufactured or become available. Enrollment will occur at up to twelve domestic clinical
      research sites.

      This study includes two cohorts. Cohort 1 will include approximately 880 individuals (50
      subjects/group; Groups 1E-11E) greater than 18 years of age and older, stratified into two
      age strata (18-55 years and >/=56 years) who previously received COVID-19 vaccine at
      Emergency Use Authorization dosing (EUA) (two vaccinations of mRNA-1273 at the 100 mcg dose,
      two vaccinations of BNT162b2 at the 30 mcg dose, or one vaccination of Ad26.COV2.S at the
      5x10^10 vp dose). Groups 15E-17E will enroll 60 subjects, split (approximately evenly)
      between age strata as able. Those subjects will be offered enrollment into this study >/=12
      weeks after they received the last dose of their EUA vaccine. Subjects will receive a single
      open-label intramuscular (IM) injection of the designated delayed booster vaccine and will be
      followed through 12 months after vaccination: 1) Group 1E - previously EUA-dosed vaccination
      with Janssen - Ad26.COV.2.S at 5x10^10 vp followed by a 100-mcg dose of mRNA-1273, Group 4E -
      previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S at 5x10^10 vp followed by a
      5x10^10 vp dose of Ad26.COV2.S, Group 7E - previously EUA-dosed vaccination with Janssen -
      Ad26.COV.2.S 5x10^10 vp followed by a 30-mcg dose of BNT162b2, Group 10E - previously
      EUA-dosed vaccination with Janssen - Ad26.COV2-S 5x10^10 vp followed by a 100-mcg dose of
      mRNA-1273.211; Group 12E - previously EUA-dosed vaccination with Janssen - Ad26.COV2-S
      5x10^10 vp followed by a 50-mcg dose of mRNA-1273; Group 15E - previously EUA-dosed
      vaccination with Janssen (two doses for Group 15E) - Ad26.COV2.S at 5x1010 vp followed by a
      dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV-2 rS vaccine with 50 mcg Matrix-M); 2) Group 2E
      - previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed
      by a 100-mcg dose of mRNA-1273, Group 5E - previously EUA-dosed vaccination with Moderna -
      mRNA-1273 at 100 mcg for two doses followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 8E -
      previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed
      by a 30-mcg dose of BNT162b2, Group 13E - previously EUA-dosed vaccination with Moderna -
      mRNA-1273 at 100 mcg for two doses followed by a 50-mcg dose of mRNA-1273; Group 16E -
      previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed
      by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV2 rS vaccine with 50 mcg Matrix-M); 3)
      Group 3E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two
      doses followed by a 100-mcg dose of mRNA-1273. Group 6E - previously EUA-dosed vaccination
      with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 5x10^10 vp dose of
      Ad26.COV2.S, Group 9E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at
      30 mcg for two doses followed by a 30-mcg dose of BNT162b2, Group 11E - previously EUA-dosed
      vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 100-mcg
      dose of mRNA-1273.211. Group 14E - previously EUA-dosed vaccination with Pfizer/BioNTech -
      BNT162b2 at 30 mcg for two doses followed by a 50-mcg dose of mRNA-1273, Group 17E -
      previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses
      followed by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV2 rS vaccine with 50 mcg
      Matrix-M).

      A telephone visit will occur one week after each primary EUA vaccination and one week after
      the booster dose. In person follow-up visits will occur on 14 days following completion of
      EUA vaccinations and on days 14, and 28 days after the booster dose, as well as 3, 6, and 12
      months post the booster vaccination. Additional pools of subjects can be included if needed
      as additional COVID-19 vaccines are awarded EUA.

      The primary objectives of this study are 1) to evaluate the safety and reactogenicity of
      delayed heterologous or homologous vaccine doses after EUA dosed vaccines, and 2) to evaluate
      the breadth of the humoral immune responses of heterologous and homologous delayed boost
      regimens following EUA dosing.
    

Detailed description: 
      A phase 1/2, open-label clinical trial in individuals, 18 years of age and older, who are in
      good health, have no known history of Coronavirus Disease 2019 (COVID-19) or Severe Acute
      Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and meet all other eligibility
      criteria. This clinical trial is designed to assess the safety, reactogenicity and
      immunogenicity of a delayed (>/=12 weeks) vaccine boost on a range of Emergency Use
      Authorization (EUA)-dosed COVID-19 vaccines (mRNA-1273, and mRNA-1273.211 manufactured by
      ModernaTX, Inc.; BNT162b2 manufactured by Pfizer/BioNTech; or Ad26.COV2.S manufactured by
      Janssen Pharmaceuticals/Johnson & Johnson). This is an adaptive design and may add arms (and
      increase sample size) as vaccines are awarded EUA and/or variant lineage spike vaccines are
      manufactured or become available. Enrollment will occur at up to twelve domestic clinical
      research sites.

      This study includes two cohorts. Cohort 1 will include approximately 880 individuals (50
      subjects/group; Groups 1E-14E, and 60 subjects/group; Groups 15E-17E) greater than 18 years
      of age and older, stratified into two age strata (18-55 years and >/=56 years) who previously
      received COVID-19 vaccine at Emergency Use Authorization dosing (EUA) (two vaccinations of
      mRNA-1273 at the 100 mcg dose, two vaccinations of BNT162b2 at the 30 mcg dose, or one
      vaccination of Ad26.COV2.S at the 5x10^10 vp dose). Groups 15E-17E will enroll 60 subjects,
      split (approximately evenly) between age strata as able. Those subjects will be offered
      enrollment into this study >/=12 weeks after they received the last dose of their EUA
      vaccine. Subjects will receive a single open-label intramuscular (IM) injection of the
      designated delayed booster vaccine and will be followed through 12 months after vaccination:
      1) Group 1E - previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S at 5x10^10 vp
      followed by a 100-mcg dose of mRNA-1273, Group 4E - previously EUA-dosed vaccination with
      Janssen - Ad26.COV.2.S at 5x10^10 vp followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 7E -
      previously EUA-dosed vaccination with Janssen - Ad26.COV.2.S 5x10^10 vp followed by a 30-mcg
      dose of BNT162b2, Group 10E - previously EUA-dosed vaccination with Janssen - Ad26.COV2-S
      5x10^10 vp followed by a 100-mcg dose of mRNA-1273.211; Group 12E - previously EUA-dosed
      vaccination with Janssen - Ad26.COV2-S 5x10^10 vp followed by a 50-mcg dose of mRNA-1273;
      Group 15E - previously EUA-dosed vaccination with Janssen (two doses for Group 15E) -
      Ad26.COV2.S at 5x1010 vp followed by a dose of NVX-CoV2373 (5 mcg Prototype SARS-CoV-2 rS
      vaccine with 50 mcg Matrix-M); 2) Group 2E - previously EUA-dosed vaccination with Moderna -
      mRNA-1273 at 100 mcg for two doses followed by a 100-mcg dose of mRNA-1273, Group 5E -
      previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed
      by a 5x10^10 vp dose of Ad26.COV2.S, Group 8E - previously EUA-dosed vaccination with Moderna
      - mRNA-1273 at 100 mcg for two doses followed by a 30-mcg dose of BNT162b2, Group 13E -
      previously EUA-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses followed
      by a 50-mcg dose of mRNA-1273; Group 16E - previously EUA-dosed vaccination with Moderna -
      mRNA-1273 at 100 mcg for two doses followed by a dose of NVX-CoV2373 (5 mcg Prototype
      SARS-CoV2 rS vaccine with 50 mcg Matrix-M); 3) Group 3E - previously EUA-dosed vaccination
      with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a 100-mcg dose of
      mRNA-1273. Group 6E - previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30
      mcg for two doses followed by a 5x10^10 vp dose of Ad26.COV2.S, Group 9E - previously
      EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a
      30-mcg dose of BNT162b2, Group 11E - previously EUA-dosed vaccination with Pfizer/BioNTech -
      BNT162b2 at 30 mcg for two doses followed by a 100-mcg dose of mRNA-1273.211. Group 14E -
      previously EUA-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses
      followed by a 50-mcg dose of mRNA-1273, Group 17E - previously EUA-dosed vaccination with
      Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses followed by a dose of NVX-CoV2373 (5 mcg
      Prototype SARS-CoV2 rS vaccine with 50 mcg Matrix-M).

      A telephone visit will occur at Day 8 and in-person follow-up visits will occur on Days 15
      and 29, as well as 3, 6, and 12 months after the vaccination. Cohort 2 will include
      approximately 250 participants per group aged >/=18 years of age who have not received a
      Coronavirus Disease 2019 (COVID-19) vaccine and have no known history of Coronavirus Disease
      2019 (COVID-19) or SARS Coronavirus 2 (SARS-CoV-2) infection. They will be assigned to
      receive COVID-19 vaccine under Emergency Use Authorization dosing (EUA) (two vaccinations of
      mRNA-1273 at the 100mcg dose at a 28 days of interval). These pools of participants will be
      assigned 50 mcg mRNA-1273 at a minimum of 12 weeks following receipt of EUA dosing and
      followed through 12 months after the last vaccination. A telephone visit will occur one week
      after each primary EUA vaccination and one week after the booster dose. In person follow-up
      visits will occur on 14 days following completion of EUA vaccinations and on days 14, and 28
      days after the booster dose, as well as 3, 6, and 12 months post the booster vaccination.
      Additional pools of subjects can be included if needed as additional COVID-19 vaccines are
      awarded EUA.

      New groups may be added to Cohort 1 or 2 dependent upon manufacture of variant lineage spike
      protein-based vaccine constructs or vaccines newly awarded EUA. The primary objectives of
      this study are 1) to evaluate the safety and reactogenicity of delayed heterologous or
      homologous vaccine doses after EUA dosed vaccines, and 2) to evaluate the breadth of the
      humoral immune responses of heterologous and homologous delayed boost regimens following EUA
      dosing.
    

Intervention name(s): Ad26.COV2.S; BNT162b2; mRNA-1273; mRNA-1273.211; mRNA-1273.222; SARS-CoV-2 rS/M1
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Biological
Intervention description(s): Formulated to contain 5x10 virus particles of the Ad26 vector encoding the S glycoprotein of SARS-CoV-2. Each dose of the Ad26.COV2.S vaccine also includes sodium chloride, citric acid monohydrate, trisodium citrate dihydrate, polysorbate-80, 2-hydroxypropyl-ß-cyclodextrin, and ethanol. Ad26.COV2.S will be used undiluted to obtain the specified vp content in 0.5 mL doses. Each dose is 0.5 mL.; A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2. Each vial contains up to six doses. BNT162b2 (250 mcg/0.5 mL) will be administered in diluted 0.3 mL doses (30 mcg/0.3 mL).; Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).; Lipid nanoparticle (LNP) dispersion containing 1:1 mix of mRNAs that encodes for the prefusion stabilized S protein of the B.1.351 variant SARS-CoV-2 strain and the prefusion stabilized S protein of the Wuhan-Hu-1 strain used in mRNA-1273. mRNA-1273.211 (0.2 mg/mL) will be administered in 0.5 mL doses (100 mcg/0.5 mL).; Formulated in the same way as the mRNA-1273 vaccine but contains 1:1 mix of mRNAs that encodes for the prefusion stabilized S protein of the Omicron BA.4/BA.5 variant SARS-CoV-2 strain and the prefusion stabilized S protein of the Wuhan-Hu-1 strain used in mRNA-1273.; SARS-CoV-2 rS Drug Substance containing the prototype Wuhan is formulated with saponin-based Matrix-M adjuvant in a buffer of 25 mM sodium phosphate (pH 7.2), 300 mM sodium chloride, and 0.01% (weight per volume [w/v]) polysorbate 80. NVX-Co-V2373 will be administered in 0.5 mL dose (5 mcg Prototype SARS-CoV-2 rS with 50 mcg Matrix-M adjuvant)
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Heterologous Nonvariant Boost; SARS-COV-2; SARS-COV-2 Vaccine