MedPath

Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines

Phase 1
Completed
Conditions
COVID-19
Interventions
Biological: mRNA-1273
Biological: mRNA-1273.211
Biological: SARS-CoV-2 rS/M1
Biological: BNT162b2
Biological: Ad26.COV2.S
Biological: mRNA-1273.222
Registration Number
NCT04889209
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
867
Inclusion Criteria

Participants must meet all of the following criteria to be eligible to participate in this study:

  1. Individuals >/= 18 years of age at the time of consent.

  2. Received and completed primary mRNA COVID-19 vaccine under EUA dosing guidelines and one or two doses of Ad26.COV2.S at least 12 weeks prior to enrollment (Cohort 1 only).

  3. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.

  4. Determined by medical history, targeted physical examination and clinical judgement of the investigator to be in good health.*

    * Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included.

  5. Female participants of childbearing potential may be enrolled in the study, if all of the following apply:

    • Practiced adequate contraception for 28 days prior to the first dose of vaccine (Day 1),
    • Has agreed to continue adequate contraception through 3 months following the booster dose,
    • Has a negative pregnancy test at screening and on the day of the first study vaccine dose (Day 1),
    • Is not currently breastfeeding.
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Exclusion Criteria

Participants meeting any of the following criteria will be excluded from the study:

  1. Known history of SARS-CoV-2 infection. (for Cohort 1 and the primary series of Cohort 2).
  2. Prior administration of an investigational coronavirus (SARS Coronavirus (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV)) vaccine or SARS Coronavirus 2 (SARS-CoV-2) monoclonal antibody in the preceding 90 days or current/planned simultaneous participation in another interventional study.
  3. Receipt of SARS Coronavirus 2 (SARS-CoV-2) vaccine prior to study entry (Cohort 2 only).
  4. A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine or nanolipid particles.
  5. Receipt of any investigational study product within 28 days prior to enrollment.
  6. Received or plans to receive a vaccine within 28 days prior to the first dose (Day 1) or plans to receive a non-study vaccine within 28 days prior to or after any dose of study vaccine (with exception for seasonal influenza vaccine within 14 days of study vaccine).
  7. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with intramuscular injections or blood draws, or previously experienced thrombosis with thrombocytopenia (TTS) or heparin-induced thrombocytopenia.
  8. Current or previous diagnosis of immunocompromising condition, immune-mediated disease, or other immunosuppressive condition.
  9. Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids >/= 20 milligram per day of prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to Day 1.
  10. Received immunoglobulin, blood-derived products, within 90 days prior to first study vaccination.
  11. An immediate family member or household member of this study's personnel.
  12. Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as >/= 38.0 degrees Celsius or 100.4 degrees Fahrenheit). Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 1 Group 12EmRNA-1273Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Janssen - Ad26.COV.2.S at 5x10\^10 vp stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 50-mcg dose of mRNA- 1273 N = 50
Cohort 1 Group 10EmRNA-1273.211Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Janssen - Ad26.COV2-S 5x10\^10 vp stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 100-mcg dose of mRNA-1273.211 (boost dose). N = 50
Cohort 1 Group 11EmRNA-1273.211Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 100-mcg dose of mRNA-1273.211 (boost dose). N = 50
Cohort 1 Group 13EmRNA-1273Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Moderna-mRNA-1273 at 100mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 50-mcg dose of mRNA-1273. N = 50
Cohort 1 Group 14EmRNA-1273Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 50-mcg dose of mRNA-1273. N = 50
Cohort 1 Group 15ESARS-CoV-2 rS/M1Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Janssen - Ad26.COV.2.S 5x10\^10 vp for one or two doses stratified with two age ranges of 18-55 years (n= 30) and 56 or older (n = 30) randomized to receive a single intramuscular (IM) injection of a 5-mcg dose of NVX-CoV2373 (SARS-COV-2). N =60
Cohort 1 Group 16ESARS-CoV-2 rS/M1Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses stratified with two age ranges of 18-55 years (n = 30) and 56 or older (n = 30) randomized to receive a single intramuscular (IM) injection of a 5-mcg dose of NVX-CoV2373 (SARS-COV-2). N =60
Cohort 1 Group 17ESARS-CoV-2 rS/M1Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses stratified with two age ranges of 18-55 years (n = 30) and 56 or older (n = 30) randomized to receive a single intramuscular (IM) injection of a 5-mcg dose of NVX-CoV2373 (SARS-COV-2). N =60
Cohort 1 Group 1EmRNA-1273Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Janssen - Ad26.COV.2.S at 5x10\^10 vp stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of 100-mcg dose of mRNA-1273 (boost dose). N = 50
Cohort 1 Group 2EmRNA-1273Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA) -dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 100-mcg dose of mRNA-1273 (boost dose). N = 50
Cohort 1 Group 3EmRNA-1273Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA) -dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n ˜ 25) randomized to receive a single intramuscular (IM) injection of a 100-mcg dose of mRNA-1273 (boost dose). N = 50
Cohort 1 Group 7EBNT162b2Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Janssen - Ad26.COV.2.S 5x10\^10 vp stratified with two age ranges of 18-55 years (n=˜ 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 30-mcg dose of BNT162b2 (boost dose). N = 50
Cohort 1 Group 8EBNT162b2Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 30-mcg dose of BNT162b2 (boost dose). N = 50
Cohort 1 Group 9EBNT162b2Adaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of a 30-mcg dose of BNT162b2 (boost dose). N = 50
Cohort 2mRNA-1273A prospective design cohort with naïve to COVID-19 vaccine and infection participants of \> / = 18 years of age to receive COVID-19 vaccine intramuscularly under Emergency Use Authorization dosing (EUA) (two vaccinations of mRNA-1273 at the 100mcg dose at a 28 days of interval) followed by a delayed vaccination (50 mcg mRNA-1273) after a minimum of 12 weeks. A second booster (fourth dose) will be administered intramuscular using Moderna mRNA-1273.222 at 50 mcg at a 4-12 month interval N=250
Cohort 2mRNA-1273.222A prospective design cohort with naïve to COVID-19 vaccine and infection participants of \> / = 18 years of age to receive COVID-19 vaccine intramuscularly under Emergency Use Authorization dosing (EUA) (two vaccinations of mRNA-1273 at the 100mcg dose at a 28 days of interval) followed by a delayed vaccination (50 mcg mRNA-1273) after a minimum of 12 weeks. A second booster (fourth dose) will be administered intramuscular using Moderna mRNA-1273.222 at 50 mcg at a 4-12 month interval N=250
Cohort 1 Group 4EAd26.COV2.SAdaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Janssen - Ad26.COV2-S at 5x10\^10 vp stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of Ad26.COV2.S 5x10\^10 vp (boost dose). N = 50
Cohort 1 Group 5EAd26.COV2.SAdaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Moderna - mRNA-1273 at 100 mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of Ad26.COV2.S 5x10\^10 vp (boost dose). N = 50
Cohort 1 Group 6EAd26.COV2.SAdaptive design cohort with participants that previously (\>/=12 weeks) received Emergency Use Authorization (EUA)-dosed vaccination with Pfizer/BioNTech - BNT162b2 at 30 mcg for two doses stratified with two age ranges of 18-55 years (n = 25) and 56 or older (n = 25) randomized to receive a single intramuscular (IM) injection of Ad26.COV2.S 5x10\^10 vp (boost dose). N = 50
Primary Outcome Measures
NameTimeMethod
Geometric Mean of Pseudovirus Neutralization Against BA.4/5 for Cohort 2Day 1 Pre-Vaccination 1, Day 43 Post-Vaccination 1, Day 15 Post-Booster Dose 1, Day 1 Pre-Booster Dose 2, Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Geometric Mean of Pseudovirus Neutralization against BA.4/5

Geometric Mean of Pseudovirus Neutralization Against XBB.1 for Cohort 2Day 1 Pre-Vaccination 1, Day 43 Post-Vaccination 1, Day 15 Post-Booster Dose 1, Day 1 Pre-Booster Dose 2, Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Geometric Mean of Pseudovirus Neutralization against XBB.1

Geometric Mean of Area Under the Curve (AUC) of Antibody Against WA-1 S2-P for Cohort 1Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Geometric Mean AUC of Antibody Against WA-1 S2-P using 10-plex ECLIA Assay. Area was computed for electrochemiluminescence signal across sample dilutions using a trapezoidal method. Units are Electrochemiluminescence (ECL) Signal x 1/dilution (integrated).

Geometric Mean of AUC of Antibody Against B.1.351 S2-P for Cohort 1Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Geometric Mean AUC of Antibody Against B.1.351 S2-P using 10-plex ECLIA Assay. Area was computed for electrochemiluminescence signal across sample dilutions using a trapezoidal method.

Geometric Mean AUC of Antibody Against B.1.617.2 S2-P for Cohort 1Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Geometric Mean AUC of Antibody Against B.1.617.2 S2-P using 10-plex ECLIA Assay. Area was computed for electrochemiluminescence signal across sample dilutions using a trapezoidal method.

Geometric Mean AUC of Antibody Against B.1.1.529 S2-P for Cohort 1Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Geometric Mean AUC of Antibody Against B.1.1.529 S2-P using 10-plex ECLIA Assay. Area was computed for electrochemiluminescence signal across sample dilutions using a trapezoidal method.

Geometric Mean AUC of Antibody of Antibody Against WA-1 S2-P for Cohort 2Day 1 Pre-Booster Dose 2, Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Geometric Mean AUC of Antibody Against WA-1 S2-P using 10-plex ECLIA Assay. Area was computed for electrochemiluminescence signal across sample dilutions using a trapezoidal method.

Geometric Mean AUC of Antibody Against BA.1 S2-P for Cohort 2Day 1 Pre-Booster Dose 2, Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Geometric Mean AUC of Antibody Against BA.1 S2-P using 10-plex ECLIA Assay. Area was computed for electrochemiluminescence signal across sample dilutions using a trapezoidal method.

Geometric Mean AUC of Antibody Against BA.5 S2-P for Cohort 2Day 1 Pre-Booster Dose 2, Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Geometric Mean AUC of Antibody Against BA.5 S2-P using 10-plex ECLIA Assay. Area was computed for electrochemiluminescence signal across sample dilutions using a trapezoidal method.

Geometric Mean of Pseudovirus Neutralization Against D614G for Cohort 1Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Geometric Mean of Pseudovirus Neutralization against D614G

Geometric Mean of Pseudovirus Neutralization Against B.1.351 for Cohort 1Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Geometric Mean of Pseudovirus Neutralization against B.1.351

Geometric Mean of Pseudovirus Neutralization Against B.1.617.2 for Cohort 1Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Geometric Mean of Pseudovirus Neutralization against B.1.617.2

Geometric Mean of Pseudovirus Neutralization Against B.1.1.529 for Cohort 1Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Geometric Mean of Pseudovirus Neutralization against B.1.1.529

Geometric Mean of Pseudovirus Neutralization Against D614G for Cohort 2Day 1 Pre-Vaccination 1, Day 43 Post-Vaccination 1, Day 15 Post-Booster Dose 1, Day 1 Pre-Booster Dose 2, Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Geometric Mean of Pseudovirus Neutralization against D614G

Geometric Mean of Pseudovirus Neutralization Against BA.1 for Cohort 2Day 1 Pre-Vaccination 1, Day 43 Post-Vaccination 1, Day 15 Post-Booster Dose 1, Day 1 Pre-Booster Dose 2, Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Geometric Mean of Pseudovirus Neutralization against BA.1

Frequency of Any Unsolicited Adverse Events (AEs)Day 1 through Day 29 for Cohort 1, 28 days post any vaccination in Cohort 2

Number of participants who experienced any unsolicited AEs through 28 days post vaccination

Frequency of Any Protocol Specified Adverse Events of Special Interest (AESIs)For Cohort 1, Day 1 through Day 366; for Cohort 2, Day 1 through Day 590

Number of participants that experienced any AESIs during the course of the study. An adverse event of special interest (serious or nonserious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is required. AESIs include anosmia, ageusia, subacute thyroiditis, acute pancreatitis, appendicitis, rhabdomyolysis, acute respiratory distress syndrome, coagulation disorders, acute cardiovascular injury, acute kidney injury, acute liver injury, dermatologic findings, multisystem inflammatory disorders, thrombocytopenia, acute aseptic arthritis, new onset of or worsening of neurologic disease, anaphylaxis, and other syndromes.

Frequency of Any New-onset Chronic Medical Conditions (NOCMCs)For Cohort 1, Day 1 through Day 366; for Cohort 2, Day 1 through Day 590

Number of participants that experienced any NOCMCs during the course of the study

Number of Participants With Any Medically-attended Adverse Events (MAAEs)For Cohort 1, Day 1 through Day 366; for Cohort 2, Day 1 through Day 590

Number of participants that experienced MAAEs during the course of the study.

Frequency of Any Serious Adverse Events (SAEs)For Cohort 1, Day 1 through Day 366; for Cohort 2, Day 1 through Day 590

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 lifethreatening 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.

Frequency of Systemic Solicited Reactogenicity Adverse Events (AEs)Day 1 through Day 8 for Cohort 1, and through 7 days post any vaccination for Cohort 2

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.

Frequency of Local Solicited Reactogenicity Adverse Events (AEs)Day 1 through Day 8 for Cohort 1, and through 7 days post any vaccination for Cohort 2

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.

Percent of Participants Who Seroconverted Against WA-1 S2-P for Cohort 1Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Percent of participants who seroconverted defined as a 4-fold change in antibody titer from baseline against WA-1 S2-P

Percent of Participants Who Seroconverted Against B.1.351 S2-P for Cohort 1Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Percent of participants who seroconverted defined as a 4-fold change in antibody titer from baseline against B.1.351 S2-P

Percent of Participants Who Seroconverted Against B.1.617.2 S2-P for Cohort 1Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Percent of participants who seroconverted defined as a 4-fold change in antibody titer from baseline against B.1.617.2 S2-P

Percent of Participants Who Seroconverted Against B.1.1.529 S2-P for Cohort 1Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Percent of participants who seroconverted defined as a 4-fold change in antibody titer from baseline against B.1.1.529 S2-P

Percent of Participants Who Seroconverted Against WA-1 S2-P for Cohort 2Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Percent of participants who seroconverted defined as a 4-fold change in antibody titer from baseline against WA-1 S2-P

Percent of Participants Who Seroconverted Against BA.1 S2-P for Cohort 2Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Percent of participants who seroconverted defined as a 4-fold change in antibody titer from baseline against BA.1 S2-P

Percent of Participants Who Seroconverted Against BA.5 S2-P for Cohort 2Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Percent of participants who seroconverted defined as a 4-fold change in antibody titer from baseline against BA.5 S2-P

Percent of Participants Who Seroconverted Against D614G for Cohort 1Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from baseline against D614G

Percent of Participants Who Seroconverted Against B.1.351 for Cohort 1Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from baseline against B.1.351

Percent of Participants Who Seroconverted Against B.1.617.2 for Cohort 1Day 15, Day 29

Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from baseline against B.1.617.2

Percent of Participants Who Seroconverted Against B.1.1.529 for Cohort 1Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from baseline against B.1.1.529

Percent of Participants Who Seroconverted Against D614G for Cohort 2Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from Pre-Dose 1 against D614G

Percent of Participants Who Seroconverted Against BA.1 for Cohort 2Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from Pre-Booster Dose 2 against BA.1

Percent of Participants Who Seroconverted Against BA.4/5 for Cohort 2Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from Pre-Booster Dose 2 against BA.4/5

Percent of Participants Who Seroconverted Against XBB.1 for Cohort 2Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from Pre-Booster Dose 2 against XBB.1

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (10)

University of Rochester Medical Center - Vaccine Research Unit

🇺🇸

Rochester, New York, United States

Cincinnati Children's Hospital Medical Center Vaccine Research Center

🇺🇸

Cincinnati, Ohio, United States

University of Pittsburgh - Medicine - Infectious Diseases

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Maryland Baltimore - Institute of Human Virology

🇺🇸

Baltimore, Maryland, United States

NYU Langone Vaccine Center

🇺🇸

New York, New York, United States

The Hope Clinic of Emory University

🇺🇸

Decatur, Georgia, United States

University of Texas Medical Branch

🇺🇸

Galveston, Texas, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Kaiser Permanente Washington Health Research Institute

🇺🇸

Seattle, Washington, United States

The University of Washington - Virology Research Clinic

🇺🇸

Seattle, Washington, United States

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