Safety, Reactogenicity, and Immunogenicity Study of Heterologous Booster Vaccination of a SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510)

A Placebo-controlled, Randomized, Observer-blinded, Multi-center Study to Assess the Safety, Reactogenicity, and Immunogenicity of Booster Vaccination of A SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510)

This is randomized, placebo-controlled, observer-blinded, multi-center study to assess safety, reactogenicity and immunogenicity of booster vaccination of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03 in adults aged 19 years and older who received a primary series of vaccination or the 1st booster vaccination against COVID-19 approved in Korea.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19 (Healthy Volunteers)
• Intervention / Treatment: Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; Other: Normal saline

Detailed Description

The purpose of this study is to assess the safety, reactogenicity and immunogenicity of booster vaccination of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510).

(Cohort 1~5) A total of approximately 550 adults will be divided into 5 cohorts based on primary series vaccines they received - ChAdOx1 nCOV-19, BNT162b2, mRNA-1273, Ad26.COV2.S and heterologous vaccination with ChAdOx1 nCOV-19 & BNT162b2.

(Cohort 6~7) A total of approximately 220 adults will be divided into 2 cohorts based on primary series & 1st booster vaccines they received -mRNA vaccines (BNT162b2 or mRNA-1273) and at least more than a single dose of non-mRNA vaccines (ChAdOx1 nCOV-19, Ad26.COV2.S, and NVX-CoV2373)

The participants are then randomized at a ratio of 10:1 to either Test Group or Placebo Group. Participants will be subject to follow-up for 12 months after receiving a single booster dose of GBP510 adjuvanted with AS03.

Blood sampling for cell-mediated immunity will be undertaken on approximately 20% of the participants in each cohort, who are selected in advance in consideration of the randomization ratio between Test Group and Placebo Group.

• Study Type: Interventional
• Enrollment (Anticipated): 770
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hee Jin Cheong, Prof.; Phone Number: 82-2-2626-3050; Email: heejinmd@korea.ac.kr

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of
    • Korea University Ansan Hospital
    • Contact: Won Suk Choi
  • Busan, Korea, Republic of
    • Dong-A University Hospital
    • Contact: Dong Sik Jeong
  • Cheongju-si, Korea, Republic of
    • Chungbuk National University Hospital
  • Daegu, Korea, Republic of
    • Kyungpook National University Hospital
    • Contact: Shin-Woo Kim
  • Gwangju, Korea, Republic of
    • Chonnam National University Hospital
    • Contact: Kyung-Hwa Park
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
    • Contact: Hee Jin Cheong, Prof.
  • Seoul, Korea, Republic of
    • Hallym University Medical Center
    • Contact: Jacob Lee
  • Suwon, Korea, Republic of
    • Ajou University Hospital
    • Contact: Eun Jin Kim
  • Wonju, Korea, Republic of
    • Wonju Severance Christian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 47 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant must be aged 19 years and older at the time of signing the informed consent.
2. Participants who are healthy or medically stabilized according to medical judgment of the investigator based on medical history, physical examination and clinical laboratory tests, etc.
3. Participants who are able to attend all scheduled visits and comply with all study procedures.
4. (Cohort 1~5) Participants who received a primary series of COVID-19 vaccination approved for use in Korea by MFDS and at least 12~24 weeks have passed with no additional COVID-19 vaccination.
5. (Cohort 6~7) Participants who received a primary series of COVID-19 vaccination and the 1st booster vaccination at least 16 weeks ago through a homologous or heterologous vaccination with mRNA vaccines (BNT162b2 (Pfizer) and mRNA-1273 (Moderna)) only or at least more than a single dose of non-mRNA vaccines (ChAdOx1 nCOV-19 (AZ), Ad26.COV2.S (Janssen), and NVX-CoV2373 (Novavax)).
6. Female participants of childbearing potential must agree to be heterosexually inactive, or agree to use at least one acceptable method of contraception from at least 4 weeks prior to the study vaccination (booster vaccination) to 12 weeks after the study vaccination.
7. Female participants with a negative urine or serum pregnancy test at screening (However, female participants who are surgically sterile or postmenopausal with amenorrhea for at least 12 months shall be excluded.
8. Participants who give signed informed consent which include compliance with the requirements and restrictions listed in the informed consent form and in the protocol.

Exclusion Criteria:

1. Any clinically significant respiratory symptoms (e.g. cough, sore throat), febrile illness (temperature >38°C), or acute illness within 72 hours prior to the study vaccination (A prospective participant should not be included until 72 hours after the condition has resolved).
2. History of virologically-confirmed COVID-19, SARS or MERS disease.
3. History of confirmed SARS-CoV-2 infection within three months before screening.
4. History of congenital or acquired immunodeficiency or autoimmune disease.
5. History of bleeding disorder including thrombocytopenia which is judged by the investigator as a contraindication for intramuscular vaccination.
6. History of hypersensitivity and severe allergic reaction (e.g. anaphylaxis, Guillain-Barre syndrome) to any components of the study intervention.
7. History of malignancy within 1 year prior to the study vaccination (Except for a participant judged by the investigator to have a low recurrence risk.)
8. Any other clinically significant conditions such as uncontrollable chronic or acute diseases which, in the opinion of the investigator, might cause a health threat to the participant or interfere with the clinical trial procedures or interpretation of the study results.
9. Any other conditions which might interfere with the evaluation of the study objectives (e.g. alcohol or drug abuse, neurologic or psychiatric conditions).
10. Female participants who are pregnant or breastfeeding.
11. History of drug administration other than COVID-19 vaccination intended to treat or prevent COVID-19.
12. History or planned other vaccination within 4 weeks prior to the study vaccination through 28 days after the study vaccination (except for influenza vaccination, which may be received at least 2 weeks prior to the study vaccination).
13. Receipt of immunoglobulins, whole blood or blood products within 12 weeks prior to the study vaccination.
14. Use of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy for at least 2 consecutive weeks within 12 weeks prior to the study vaccination or long-term systemic corticosteroid therapy (e.g. ≥10mg prednisone/day or equivalent for more than 2 consecutive weeks) (However, the use of topical and nasal glucocorticoids will be permitted.)
15. History of participation in another clinical study within 4 weeks prior to the study vaccination or planned participation in another clinical study during this study period.
16. Investigators, study staff who are directly involved in the conduct of this study or supervised by the investigator, or their family members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Test group 1: primary vaccination completed with ChAdOx1 nCOV-19; GBP510 adjuvanted with AS03 (Receptor Binding Domain (RBD) 25μg/dose), 1 dose on Days 0	Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03, 1 dose
PLACEBO_COMPARATOR: Placebo group 1: primary vaccination completed with ChAdOx1 nCOV-19; Participants will receive intramuscular (IM) injections of Normal saline on Days 0	Other: Normal saline; Normal saline
EXPERIMENTAL: Test group 2: primary vaccination completed with BNT162b2(Pfizer); GBP510 adjuvanted with AS03 (Receptor Binding Domain (RBD) 25μg/dose), 1 dose on Days 0	Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03, 1 dose
PLACEBO_COMPARATOR: Placebo group 2: primary vaccination completed with BNT162b2(Pfizer); Participants will receive intramuscular (IM) injections of Normal saline on Days 0	Other: Normal saline; Normal saline
EXPERIMENTAL: Test group 3: primary vaccination completed with mRNA-1273(Moderna); GBP510 adjuvanted with AS03 (Receptor Binding Domain (RBD) 25μg/dose), 1 dose on Days 0	Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03, 1 dose
PLACEBO_COMPARATOR: Placebo group 3: primary vaccination completed with mRNA-1273(Moderna); Participants will receive intramuscular (IM) injections of Normal saline on Days 0	Other: Normal saline; Normal saline
EXPERIMENTAL: Test group 4: primary vaccination completed with Ad26.COV2.S(Janssen); GBP510 adjuvanted with AS03 (Receptor Binding Domain (RBD) 25μg/dose), 1 dose on Days 0	Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03, 1 dose
PLACEBO_COMPARATOR: Placebo group 4: primary vaccination completed with Ad26.COV2.S(Janssen); Participants will receive intramuscular (IM) injections of Normal saline on Days 0	Other: Normal saline; Normal saline
EXPERIMENTAL: Test group 5: primary vaccination completed with ChAdOx1 nCOV-19(AZ)-BNT162b2(Pfizer); GBP510 adjuvanted with AS03 (Receptor Binding Domain (RBD) 25μg/dose), 1 dose on Days 0	Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03, 1 dose
PLACEBO_COMPARATOR: Placebo group 5: primary vaccination completed with ChAdOx1 nCOV-19-BNT162b2; Participants will receive intramuscular (IM) injections of Normal saline on Days 0	Other: Normal saline; Normal saline
EXPERIMENTAL: Test group 6: primary and 1st booster vaccination completed with mRNA vaccine; GBP510 adjuvanted with AS03 (Receptor Binding Domain (RBD) 25μg/dose), 1 dose on Days 0	Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03, 1 dose
PLACEBO_COMPARATOR: Placebo group 6: primary and 1st booster vaccination completed with mRNA vaccine; Participants will receive intramuscular (IM) injections of Normal saline on Days 0	Other: Normal saline; Normal saline
EXPERIMENTAL: Test group 7: primary and 1st booster vaccination completed with ≥1 dose of non-mRNA vaccine; GBP510 adjuvanted with AS03 (Receptor Binding Domain (RBD) 25μg/dose), 1 dose on Days 0	Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03, 1 dose
PLACEBO_COMPARATOR: Placebo group 7: primary and 1st booster vaccination completed with ≥1 dose of non-mRNA vaccine; Participants will receive intramuscular (IM) injections of Normal saline on Days 0	Other: Normal saline; Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparative GMT (Geometric Mean Titer) of neutralizing antibody to SARS-CoV-2 between the Test Group and Placebo Group, measured by wild-type virus neutralization assay at 2 weeks post heterologous booster vaccination	Through Day 365 post last vaccination
GMT (Geometric Mean Titer) of SARS-CoV-2 RBD-binding antibody measured by ECLIA at each time point post heterologous booster vaccination	Through Day 365 post last vaccination
GMFR (Geometric Mean Fold Rise) of SARS-CoV-2 RBD-binding antibody from baseline measured by ECLIA at each time point post heterologous booster vaccination	Through Day 365 post last vaccination
Percentage of participants with ≥4-fold rise from baseline in SARS-CoV-2 RBD-binding antibody measured by ECLIA at each time point post heterologous booster vaccination	Through Day 365 post last vaccination
GMT (Geometric Mean Titer) of neutralizing antibody to SARS-CoV-2 measured by wild-type virus neutralization assay at each time point post heterologous booster vaccination	Through Day 365 post last vaccination
GMFR (Geometric Mean Fold Rise) of neutralizing antibody to SARS-CoV-2 from baseline measured by wild-type virus neutralization assay at each time point post heterologous booster vaccination	Through Day 365 post last vaccination
Percentage of participants with ≥4-fold rise from baseline in neutralizing antibody to SARS-CoV-2 measured by wild-type virus neutralization assay at each time point post heterologous booster vaccination	Through Day 365 post last vaccination
(Only applicable to CMI analysis set) Cell-mediated immunity assessment using IFN-γ ELISpot at each time point post heterologous booster vaccination	Through Day 365 post last vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Occurrence of immediate systemic reactions	in 30 minutes post heterologous booster vaccination
Occurrence of solicited local AEs during 7 days post heterologous booster vaccination	Through 7 days post-vaccination
Occurrence of solicited systemic AEs during 7 days post heterologous booster vaccination	Through 7 days post-vaccination
Occurrence of unsolicited AEs during 28 days post heterologous booster vaccination	Through 28 days post-vaccination
Occurrence of SAEs, MAAEs and AESIs during the study period	Through Day 0 to Day 365 post vaccination

Collaborators and Investigators

• Sponsor: Korea University Guro Hospital
• Collaborators: Korean Center for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 24, 2022
• Primary Completion (ANTICIPATED): August 1, 2023
• Study Completion (ANTICIPATED): November 1, 2023

Study Registration Dates

• First Submitted: January 3, 2022
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (ACTUAL): January 4, 2022

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 12, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: IIS_2021_001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No