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

NCT04889209 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 21-00125UM1AI148684-02
• Study Type: interventional
• Target: 867
• Locations: 1 country
• Sites: 10

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.

Conditions

COVID-19

Keywords

Heterologous Nonvariant Boost; SARS-COV-2; SARS-COV-2 Vaccine

Outcome Measures

Primary Outcomes (41)

• Geometric Mean of Area Under the Curve (AUC) of Antibody Against WA-1 S2-P for Cohort 1

  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).

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Geometric Mean of AUC of Antibody Against B.1.351 S2-P for Cohort 1

  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.

  Day 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 for Cohort 1

  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.

  Day 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 for Cohort 1

  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.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Geometric Mean AUC of Antibody of Antibody Against WA-1 S2-P for Cohort 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.

  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 AUC of Antibody Against BA.1 S2-P for Cohort 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.

  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 AUC of Antibody Against BA.5 S2-P for Cohort 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.

  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 for Cohort 1

  Geometric Mean of Pseudovirus Neutralization against D614G

  Day 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 for Cohort 1

  Geometric Mean of Pseudovirus Neutralization against B.1.351

  Day 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 for Cohort 1

  Geometric Mean of Pseudovirus Neutralization against B.1.617.2

  Day 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 for Cohort 1

  Geometric Mean of Pseudovirus Neutralization against B.1.1.529

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Geometric Mean of Pseudovirus Neutralization Against D614G for Cohort 2

  Geometric Mean of Pseudovirus Neutralization against D614G

  Day 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 for Cohort 2

  Geometric Mean of Pseudovirus Neutralization against BA.1

  Day 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 for Cohort 2

  Geometric Mean of Pseudovirus Neutralization against BA.4/5

  Day 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 for Cohort 2

  Geometric Mean of Pseudovirus Neutralization against XBB.1

  Day 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

• 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 Cohort 1, 28 days post any vaccination in Cohort 2

• Frequency of Any Protocol Specified Adverse Events of Special Interest (AESIs)

  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.

  For Cohort 1, Day 1 through Day 366; for Cohort 2, Day 1 through Day 590

• Frequency of Any New-onset Chronic Medical Conditions (NOCMCs)

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

  For Cohort 1, Day 1 through Day 366; for Cohort 2, Day 1 through Day 590

• Number of Participants With Any Medically-attended Adverse Events (MAAEs)

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

  For Cohort 1, Day 1 through Day 366; for Cohort 2, Day 1 through Day 590

• 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 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.

  For Cohort 1, Day 1 through Day 366; for Cohort 2, Day 1 through Day 590

• 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 Cohort 1, and through 7 days post any vaccination for Cohort 2

• 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 Cohort 1, and through 7 days post any vaccination for Cohort 2

• Percent of Participants Who Seroconverted Against WA-1 S2-P for Cohort 1

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

  Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Percent of Participants Who Seroconverted Against B.1.351 S2-P for Cohort 1

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

  Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Percent of Participants Who Seroconverted Against B.1.617.2 S2-P for Cohort 1

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

  Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Percent of Participants Who Seroconverted Against B.1.1.529 S2-P for Cohort 1

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

  Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Percent of Participants Who Seroconverted Against WA-1 S2-P for Cohort 2

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

  Day 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 Against BA.1 S2-P for Cohort 2

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

  Day 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 Against BA.5 S2-P for Cohort 2

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

  Day 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 Against D614G for Cohort 1

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

  Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Percent of Participants Who Seroconverted Against B.1.351 for Cohort 1

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

  Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Percent of Participants Who Seroconverted Against B.1.617.2 for Cohort 1

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

  Day 15, Day 29

• Percent of Participants Who Seroconverted Against B.1.1.529 for Cohort 1

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

  Day 15, Day 29, Day 91, Day 181, Day 273, Day 366

• Percent of Participants Who Seroconverted Against D614G for Cohort 2

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

  Day 43 Post-Dose 1, Day 15 Post Booster Dose 1

• Percent of Participants Who Seroconverted Against BA.1 for Cohort 2

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

  Day 43 Post-Dose 1, Day 15 Post Booster Dose 1

• Percent of Participants Who Seroconverted Against BA.4/5 for Cohort 2

  Percent of participants who seroconverted defined as a 4-fold change in pseudovirus neutralization from Pre-Dose 1 against BA.4/5

  Day 43 Post-Dose 1, Day 15 Post Booster Dose 1

• Percent of Participants Who Seroconverted Against XBB.1 for Cohort 2

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

  Day 43 Post-Dose 1, Day 15 Post Booster Dose 1

• Percent of Participants Who Seroconverted Against D614G for Cohort 2

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

  Day 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 Against BA.1 for Cohort 2

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

  Day 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 Against BA.4/5 for Cohort 2

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

  Day 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 Against XBB.1 for Cohort 2

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

  Day 15 Post-Booster Dose 2, Day 29 Post-Booster Dose 2, Day 91 Post-Booster Dose 2, Day 181 Post-Booster Dose 2

Study Arms (18)

Cohort 1 Group 10E

EXPERIMENTAL

Adaptive 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

Biological: mRNA-1273.211

Cohort 1 Group 11E

EXPERIMENTAL

Adaptive 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

Biological: mRNA-1273.211

Cohort 1 Group 12E

EXPERIMENTAL

Adaptive 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

Biological: mRNA-1273

Cohort 1 Group 13E

EXPERIMENTAL

Adaptive 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

Biological: mRNA-1273

Cohort 1 Group 14E

EXPERIMENTAL

Adaptive 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

Biological: mRNA-1273

Cohort 1 Group 15E

EXPERIMENTAL

Adaptive 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

Biological: SARS-CoV-2 rS/M1

Cohort 1 Group 16E

EXPERIMENTAL

Adaptive 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

Biological: SARS-CoV-2 rS/M1

Cohort 1 Group 17E

EXPERIMENTAL

Adaptive 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

Biological: SARS-CoV-2 rS/M1

Cohort 1 Group 1E

EXPERIMENTAL

Adaptive 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

Biological: mRNA-1273

Cohort 1 Group 2E

EXPERIMENTAL

Adaptive 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

Biological: mRNA-1273

Cohort 1 Group 3E

EXPERIMENTAL

Adaptive 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

Biological: mRNA-1273

Cohort 1 Group 4E

EXPERIMENTAL

Adaptive 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

Biological: Ad26.COV2.S

Cohort 1 Group 5E

EXPERIMENTAL

Adaptive 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

Biological: Ad26.COV2.S

Cohort 1 Group 6E

EXPERIMENTAL

Adaptive 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

Biological: Ad26.COV2.S

Cohort 1 Group 7E

EXPERIMENTAL

Adaptive 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

Biological: BNT162b2

Cohort 1 Group 8E

EXPERIMENTAL

Adaptive 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

Biological: BNT162b2

Cohort 1 Group 9E

EXPERIMENTAL

Adaptive 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

Biological: BNT162b2

Cohort 2

EXPERIMENTAL

A 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

Biological: mRNA-1273; Biological: mRNA-1273.222

Interventions

Ad26.COV2.S BIOLOGICAL

Formulated to contain 5x10\^10 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.

Cohort 1 Group 4E; Cohort 1 Group 5E; Cohort 1 Group 6E

BNT162b2 BIOLOGICAL

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).

Cohort 1 Group 7E; Cohort 1 Group 8E; Cohort 1 Group 9E

mRNA-1273 BIOLOGICAL

Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV). Doses are either 0.25 mL or 0.5 mL.

Cohort 1 Group 12E; Cohort 1 Group 13E; Cohort 1 Group 14E; Cohort 1 Group 1E; Cohort 1 Group 2E; Cohort 1 Group 3E; Cohort 2

mRNA-1273.211 BIOLOGICAL

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).

Cohort 1 Group 10E; Cohort 1 Group 11E

mRNA-1273.222 BIOLOGICAL

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.

Cohort 2

SARS-CoV-2 rS/M1 BIOLOGICAL

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)

Cohort 1 Group 15E; Cohort 1 Group 16E; Cohort 1 Group 17E

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be eligible to participate in this study:
• Individuals \>/= 18 years of age at the time of consent.
• 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).
• Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.
• 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.
• 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.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded from the study:
• Known history of SARS-CoV-2 infection. (for Cohort 1 and the primary series of Cohort 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.
• Receipt of SARS Coronavirus 2 (SARS-CoV-2) vaccine prior to study entry (Cohort 2 only).
• A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine or nanolipid particles.
• Receipt of any investigational study product within 28 days prior to enrollment.
• 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).
• 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.
• Current or previous diagnosis of immunocompromising condition, immune-mediated disease, or other immunosuppressive condition.
• 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.
• Received immunoglobulin, blood-derived products, within 90 days prior to first study vaccination.
• An immediate family member or household member of this study's personnel.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (10)

The Hope Clinic of Emory University

Decatur, Georgia, 30030-1705, United States

Location

University of Maryland Baltimore - Institute of Human Virology

Baltimore, Maryland, 21201-1009, United States

Location

NYU Langone Vaccine Center

New York, New York, 10016, United States

Location

University of Rochester Medical Center - Vaccine Research Unit

Rochester, New York, 14642, United States

Location

Cincinnati Children's Hospital Medical Center Vaccine Research Center

Cincinnati, Ohio, 45206-1613, United States

Location

University of Pittsburgh - Medicine - Infectious Diseases

Pittsburgh, Pennsylvania, 15213-3205, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0435, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-3411, United States

Location

Kaiser Permanente Washington Health Research Institute

Seattle, Washington, 98101-1466, United States

Location

The University of Washington - Virology Research Clinic

Seattle, Washington, 98104, United States

Location

Related Publications (5)

• Atmar RL, Lyke KE, Posavad CM, Deming ME, Brady RC, Dobrzynski D, Edupuganti S, Mulligan MJ, Rupp RE, Rostad CA, Jackson LA, Martin JM, Shriver MC, Rajakumar K, Coler RN, El Sahly HM, Kottkamp AC, Branche AR, Frenck RW, Johnston C, Babu TM, Backer M, Archer JI, Crandon S, Nakamura A, Nayak SU, Szydlo D, Dominguez Islas CP, Brown ER, O'Connell SE, Montefiori DC, Eaton A, Neuzil KM, Stephens DS, Beigel JH, Pasetti M, Roberts PC. Mucosal and Systemic Antibody Responses After Boosting With a Bivalent Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine. J Infect Dis. 2025 Oct 15;232(4):971-981. doi: 10.1093/infdis/jiaf176.

  PMID: 40298376 DERIVED

• Marchese AM, Rousculp M, Macbeth J, Beyhaghi H, Seet BT, Toback S. The Novavax Heterologous Coronavirus Disease 2019 Booster Demonstrates Lower Reactogenicity Than Messenger RNA: A Targeted Review. J Infect Dis. 2024 Aug 16;230(2):e496-e502. doi: 10.1093/infdis/jiad519.

  PMID: 37992183 DERIVED

• Lyke KE, Atmar RL, Dominguez Islas C, Posavad CM, Deming ME, Branche AR, Johnston C, El Sahly HM, Edupuganti S, Mulligan MJ, Jackson LA, Rupp RE, Rostad CA, Coler RN, Backer M, Kottkamp AC, Babu TM, Dobrzynski D, Martin JM, Brady RC, Frenck RW Jr, Rajakumar K, Kotloff K, Rouphael N, Szydlo D, PaulChoudhury R, Archer JI, Crandon S, Ingersoll B, Eaton A, Brown ER, McElrath MJ, Neuzil KM, Stephens DS, Post DJ, Lin BC, Serebryannyy L, Beigel JH, Montefiori DC, Roberts PC; DMID 21-0012 Study Group. Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants. NPJ Vaccines. 2023 Jul 11;8(1):98. doi: 10.1038/s41541-023-00693-z.

  PMID: 37433788 DERIVED

• Lyke KE, Atmar RL, Islas CD, Posavad CM, Szydlo D, Paul Chourdhury R, Deming ME, Eaton A, Jackson LA, Branche AR, El Sahly HM, Rostad CA, Martin JM, Johnston C, Rupp RE, Mulligan MJ, Brady RC, Frenck RW Jr, Backer M, Kottkamp AC, Babu TM, Rajakumar K, Edupuganti S, Dobrzynski D, Coler RN, Archer JI, Crandon S, Zemanek JA, Brown ER, Neuzil KM, Stephens DS, Post DJ, Nayak SU, Suthar MS, Roberts PC, Beigel JH, Montefiori DC; DMID 21-0012 Study Group. Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant. Cell Rep Med. 2022 Jul 19;3(7):100679. doi: 10.1016/j.xcrm.2022.100679. Epub 2022 Jun 20.

  PMID: 35798000 DERIVED

• Atmar RL, Lyke KE, Deming ME, Jackson LA, Branche AR, El Sahly HM, Rostad CA, Martin JM, Johnston C, Rupp RE, Mulligan MJ, Brady RC, Frenck RW Jr, Backer M, Kottkamp AC, Babu TM, Rajakumar K, Edupuganti S, Dobrzynski D, Coler RN, Posavad CM, Archer JI, Crandon S, Nayak SU, Szydlo D, Zemanek JA, Dominguez Islas CP, Brown ER, Suthar MS, McElrath MJ, McDermott AB, O'Connell SE, Montefiori DC, Eaton A, Neuzil KM, Stephens DS, Roberts PC, Beigel JH; DMID 21-0012 Study Group. Homologous and Heterologous Covid-19 Booster Vaccinations. N Engl J Med. 2022 Mar 17;386(11):1046-1057. doi: 10.1056/NEJMoa2116414. Epub 2022 Jan 26.

  PMID: 35081293 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Ad26COVS1; BNT162 Vaccine; 2019-nCoV Vaccine mRNA-1273

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

COVID-19 Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens; Biological Factors

Results Point of Contact

• Title: Dr. Robert L. Atmar
• Organization: Baylor College of Medicine

ratmar@bcm.edu

713-798-6849

Study Officials

• Kirsten E Lyke, M.D.

  University of Maryland School of Medicine, Center for Vaccine Development and Global Health

  STUDY CHAIR

• Robert L Atmar, M.D.

  Baylor College of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: study sites will administer product to which they have been assigned
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 17, 2021
• Study Start: May 28, 2021
• Primary Completion: June 16, 2023
• Study Completion: June 16, 2023
• Last Updated: April 20, 2025
• Results First Posted: December 11, 2024

Record last verified: 2024-07-08

Locations

US (10)