A Controlled Phase 2/3 Study of Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Vaccine (SCB-2019) for the Prevention of COVID-19 (SCB-2019)

• ClinicalTrials.gov Identifier: NCT04672395
• Recruitment Status: Recruiting
• First Posted: December 17, 2020
• Last Update Posted: February 24, 2022
• Sponsor: Clover Biopharmaceuticals AUS Pty Ltd
• Collaborators: Coalition for Epidemic Preparedness Innovations; International Vaccine Institute
• Information provided by (Responsible Party): Clover Biopharmaceuticals AUS Pty Ltd

Tracking Information

• First Submitted Date: December 16, 2020
• First Posted Date: December 17, 2020
• Last Update Posted Date: February 24, 2022
• Actual Study Start Date: March 24, 2021
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2022)

• Number of Participants with a First Occurrence of COVID-19 of Any Severity Starting 14 Days after Second Dose of SCB-2019 [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 8 (7 days after first dose) and up to Day 29 (7 days after second dose) ]
• Number of Participants with Unsolicited AEs [ Time Frame: Up to Day 43 (21 days after each dose) ]
• Number of Participants with Serious Adverse Events (SAEs), or Medically Attended AEs (MAAEs), or AEs Leading to Early Termination, or Adverse Events of Special Interest (AESIs) [ Time Frame: Up to Day 389 (1 year after second dose) ]
• Non-inferiority of the neutralizing titers after third dose compared to the neutralizing titers after second dose [ Time Frame: 14 days after third dose ]

Original Primary Outcome Measures (submitted: December 16, 2020)

• Number of Participants with a First Occurrence of COVID-19 of Any Severity Starting 14 Days after Second Dose of SCB-2019 [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of Moderate-to-Severe COVID-19 Starting 14 Days after Second Dose of SCB-2019 [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 8 (7 days after first dose) and up to Day 29 (7 days after second dose) ]
• Number of Participants with Unsolicited AEs [ Time Frame: Up to Day 43 (21 days after each dose) ]
• Number of Participants with Serious Adverse Events (SAEs), or Medically Attended AEs (MAAEs), or AEs Leading to Early Termination, or Adverse Events of Special Interest (AESIs) [ Time Frame: Up to Day 389 (1 year after second dose) ]

Current Secondary Outcome Measures (submitted: February 7, 2022)

• Number of Participants with a First Occurrence of Moderate-to-Severe COVID-19 Starting 14 Days after Second Dose of SCB-2019 [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with First Occurrence of Any Laboratory-Confirmed SARS-CoV-2 infection Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with First Occurrence of Any Laboratory-Confirmed Asymptomatic SARS-CoV-2 infection Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Burden of Disease Score of COVID-19 or SARS-CoV-2 Infection Cases Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of COVID-19 of Any Severity, Associated with Hospitalization, Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of SCB-2019 or Placebo, regardless of evidence of prior SARS-CoV-2 Infection [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of SCB-2019 or Placebo, regardless of risk of severe COVID-19 [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of COVID-19 Starting 14 days after First Dose of SCB-2019 or Placebo [ Time Frame: Day 15 up to Day 389 (1 year after second dose) ]
• Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Number of Participants with Seroconversion for SARS-CoV-2 Specific nAb [ Time Frame: Day 22, and Day 35 ]
• Geometric Mean Titer (GMT) of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Number of Participants with Seroconversion for of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor [ Time Frame: Day 22, and Day 35 ]
• Geometric Mean Titer (GMT) of SCB-2019 binding antibody [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Geometric Mean Fold Rise (GMFR) of SCB-2019 binding antibody [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Number of Participants with Seroconversion for SCB-2019 binding antibody [ Time Frame: Day 22, and Day 35 ]
• Geometric Mean Titer (GMT) of Trimer-Tag binding antibody [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Geometric Mean Fold Rise (GMFR) of Trimer-Tag binding antibody [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Non-inferiority of the neutralising titers in adolescents versus young adults. [ Time Frame: 14 days after second dose ]
• Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to 7 days after booster dose ]
• Number of Participants with Unsolicited AEs [ Time Frame: Up to 21 days after booster dose ]
• Number of Participants with Serious Adverse Events (SAEs), or Medically Attended AEs (MAAEs), or AEs Leading to Early Termination, or Adverse Events of Special Interest (AESIs) [ Time Frame: Up to 6 months after booster dose ]

Original Secondary Outcome Measures (submitted: December 16, 2020)

• Number of Participants with First Occurrence of Any Laboratory-Confirmed SARS-CoV-2 infection Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with First Occurrence of Any Laboratory-Confirmed Asymptomatic SARS-CoV-2 infection Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Burden of Disease Score of COVID-19 or SARS-CoV-2 Infection Cases Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of COVID-19 of Any Severity, Associated with Hospitalization, Starting 14 Days after Second Dose of SCB-2019 or Placebo [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of SCB-2019 or Placebo, regardless of evidence of prior SARS-CoV-2 Infection [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of SCB-2019 or Placebo, regardless of risk of severe COVID-19 [ Time Frame: Day 36 up to Day 389 (1 year after second dose) ]
• Number of Participants with a First Occurrence of COVID-19 Starting 14 days after First Dose of SCB-2019 or Placebo [ Time Frame: Day 15 up to Day 389 (1 year after second dose) ]
• Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Number of Participants with Seroconversion for SARS-CoV-2 Specific nAb [ Time Frame: Day 22, and Day 35 ]
• Geometric Mean Titer (GMT) of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Number of Participants with Seroconversion for of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor [ Time Frame: Day 22, and Day 35 ]
• Geometric Mean Titer (GMT) of SCB-2019 binding antibody [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Geometric Mean Fold Rise (GMFR) of SCB-2019 binding antibody [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Number of Participants with Seroconversion for SCB-2019 binding antibody [ Time Frame: Day 22, and Day 35 ]
• Geometric Mean Titer (GMT) of Trimer-Tag binding antibody [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]
• Geometric Mean Fold Rise (GMFR) of Trimer-Tag binding antibody [ Time Frame: Day 1, Day 22, Day 35, Day 205, and Day 389 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Controlled Phase 2/3 Study of Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Vaccine (SCB-2019) for the Prevention of COVID-19
• Official Title: A Double-blind, Randomized, Controlled, Phase 2/3 Study to Evaluate the Efficacy, Immunogenicity, and Safety of CpG 1018/Alum-Adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) for the Prevention of SARS-CoV-2- Mediated COVID-19 in Participants Aged 12 Years and Older
• Brief Summary: The purpose of this double-blind, randomized, controlled study is to evaluate the efficacy, immunogenicity, reactogenicity and safety of an adjuvanted recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) trimeric spike (S)-protein subunit vaccine (SCB-2019) for the prevention of SARS-CoV-2-mediated COVID-19 in Participants Aged 12 Years and Older.

Detailed Description

This study will assess the efficacy against COVID-19, immunogenicity, reactogenicity, and safety of CpG 1018/Alum-adjuvated SCB-2019 vaccine. The COVID-19 pandemic has resulted in high morbidity and mortality, caused major disruption to healthcare systems, and has had significant socioeconomic impacts. Currently, only limited treatment options are available against COVID-19 and accelerated vaccine development is urgently needed. Several COVID-19 vaccines were recently authorized in some countries, but the global supply is insufficient for pandemic control. Additional safe and effective vaccines for COVID-19 prevention would have significant public health impact.

Placebo recipients will be offered two doses of SCB-2019 vaccine at defined points as part of the study.

Adults participants who received SCB-2019 vaccine, will be given a third dose of the SCB-2019 vaccine at least 4 months after the second dose to assess the safety and efficacy of a booster (third) dose.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Each subject will receive 2 doses of their assigned treatment on Days 1 and 22. Booster dose will be given at least 4 months after the second dose. The treatment will be administered IM in the deltoid region of the upper non-dominant arm

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention

• Condition: COVID-19

Intervention

• Biological: CpG 1018/Alum-adjuvanted SCB-2019 vaccine
  Group 1: Participants will receive 1 intramuscular (IM) injection of 30 microgram (ug) SCB-2019 with CpG1018/Alum adjuvant on Day 1 and on Day 22
• Biological: Placebo; 0.9% saline
  Group 2: Participants will receive 1 IM injection of SCB-2019-matching placebo on Day 1 and on Day 22
• Biological: SCB-2019 vaccine
  Participants will receive 1 IM injection of 30 microgram (ug) SCB-2019 with CpG 1018/alum adjuvant
• Biological: SCB-2019 vaccine for Placebo
  Participants will receive 2 IM injection of 30 microgram (ug) SCB-2019 with CpG 1018/alum adjuvant, 21 days apart

Study Arms

• Experimental: Group 1
  CpG 1018/Alum-adjuvanted SCB-2019 vaccine
  Intervention: Biological: CpG 1018/Alum-adjuvanted SCB-2019 vaccine
• Placebo Comparator: Group 2
  Placebo Comparator: Group 20.9% Saline
  Intervention: Biological: Placebo; 0.9% saline
• Experimental: Booster dose of SCB-2019
  Adult SCB-2019 recipients will receive 1 dose of SCB-2019 at least 4 months after the second dose
  Intervention: Biological: SCB-2019 vaccine
• Placebo Comparator: Vaccination of placebo recipients with SCB-2019
  Placebo participants will be offered two doses of SCB-2019 vaccine
  Intervention: Biological: SCB-2019 vaccine for Placebo

Publications *

• Liu H, Su D, Zhang J, Ge S, Li Y, Wang F, Gravel M, Roulston A, Song Q, Xu W, Liang JG, Shore G, Wang X, Liang P. Improvement of Pharmacokinetic Profile of TRAIL via Trimer-Tag Enhances its Antitumor Activity in vivo. Sci Rep. 2017 Aug 21;7(1):8953. doi: 10.1038/s41598-017-09518-1. Erratum in: Sci Rep. 2018 Mar 22;8(1):5266.
• Rüggeberg JU, Gold MS, Bayas JM, Blum MD, Bonhoeffer J, Friedlander S, de Souza Brito G, Heininger U, Imoukhuede B, Khamesipour A, Erlewyn-Lajeunesse M, Martin S, Mäkelä M, Nell P, Pool V, Simpson N; Brighton Collaboration Anaphylaxis Working Group. Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2007 Aug 1;25(31):5675-84. Epub 2007 Mar 12.
• Rhodes SJ, Knight GM, Kirschner DE, White RG, Evans TG. Dose finding for new vaccines: The role for immunostimulation/immunodynamic modelling. J Theor Biol. 2019 Mar 21;465:51-55. doi: 10.1016/j.jtbi.2019.01.017. Epub 2019 Jan 10.
• Food and Drug Administration letter. Device: BinaxNOW COVID-19 Ag Card. 26 August 2020. https://www.fda.gov/media/141567/download. Accessed on 15 September 2020.
• Food and Drug Administration Guidance Document: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Available at https://www.fda.gov/media/73679/download. Accessed on 15 September 2020.
• Safety Platform for Emergency vACcines (SPEAC). D2.3 Priority List of Adverse Events of Special Interest: COVID-19. V1.1 Date 05 March 2020. https://media.tghn.org/articles/COVID-19_AESIs_SPEAC_V1.1_5Mar2020.pdf. Accessed on 15 September 2020.
• Chan ISF, Bohidar NR (1998) Exact power and sample size for vaccine efficacy studies, Communications in Statistics - Theory and Methods 1998;27(6):1305-22.
• Maurer W, Bretz F. Multiple testing in group sequential trials using graphical approaches. Stat Biopharm Res 2013;5(4):311-20.
• Bravo L, Smolenov I, Han HH, Li P, Hosain R, Rockhold F, Clemens SAC, Roa C Jr, Borja-Tabora C, Quinsaat A, Lopez P, López-Medina E, Brochado L, Hernández EA, Reynales H, Medina T, Velasquez H, Toloza LB, Rodriguez EJ, de Salazar DIM, Rodríguez CA, Sprinz E, Cerbino-Neto J, Luz KG, Schwarzbold AV, Paiva MS, Carlos J, Montellano MEB, de Los Reyes MRA, Yu CY, Alberto ER, Panaligan MM, Salvani-Bautista M, Buntinx E, Hites M, Martinot JB, Bhorat QE, Badat A, Baccarini C, Hu B, Jurgens J, Engelbrecht J, Ambrosino D, Richmond P, Siber G, Liang J, Clemens R. Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2022 Jan 29;399(10323):461-472. doi: 10.1016/S0140-6736(22)00055-1. Epub 2022 Jan 20.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 7, 2022): 30000
• Original Estimated Enrollment (submitted: December 16, 2020): 34000
• Estimated Study Completion Date: July 2022
• Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or females ≥12 years of age, inclusive*.
2. Participants who are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, the electronic completion of the COVID-19 ePRO and other study procedures.
3. Healthy adult or adolescent subjects or adult or adolescent subjects with pre-existing medical conditions who are in stable condition.

4. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment *

   *Note: The first 200 individuals enrolled in the Phase 2 part of the study should be healthy subjects 18 to 64 years or age without comorbidities associated with a high risk of severe COVID-19

5. Female subjects who are WOCBP are eligible to participate in the study if not pregnant, not breastfeeding, and at least 1 of the following criteria apply:

   • WOCBP must have a negative urine pregnancy test prior to each vaccination. A confirmatory serum pregnancy test may be conducted at the investigator's discretion.
   • They must be using a highly effective licensed method of birth control for 30 days prior to the first vaccination and must agree to continue such precautions during the study until 90 days after the second vaccination.
6. Male subjects must agree to employ acceptable contraception from the day of first dose of the study vaccine/placebo until 6 months after the last dose of the study vaccine/placebo and also refrain from donating sperm during this period.
7. Individuals (or their legally acceptable representative based on local regulations) willing and able to give an informed consent, prior to screening. For adolescent subjects: informed assent signed by adolescents and informed consent signed by the parent(s) or legally acceptable representative(s) as per local requirements.
8. Applicable for HIV-positive individuals only:

Exclusion Criteria:

1. Individuals with laboratory-confirmed SARS-CoV-2 infection (e.g., a positive RT-PCR* or Rapid COVID-19 Antigen test) at screening or within 14 days prior to enrollment.
2. Individuals with behavioral or cognitive impairment (including drug and alcohol abuse) inthe opinion of the investigator.
3. Individuals with any progressive or severe neurologic disorder, seizure disorder, or history of Guillian-Barré syndrome.
4. Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, e.g., for cancer or an autoimmune disease, or planned receipt during the study period.
5. Individuals who are pregnant, or breastfeeding, or planning to become pregnant during the study period.
6. Individuals who have a history of severe adverse reaction associated with a vaccine or severe allergic reaction (e.g., anaphylaxis) to any component of the study vaccine (SCB-2019, CpG1018 Adjuvant and Aluminum hydroxide components as outlined in the latest IB).
7. Individuals who have a history of malignancy within 1 year before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix which have been cured, or other malignancies with minimal risk of recurrence).
8. Individuals who have received any other investigational product within 30 days prior to Day 1 or intent to participate in another clinical study at any time during the conduct of this study.
9. Individuals who have received previous vaccination with any coronavirus vaccine.
10. Individuals who have received any other licensed vaccines within 14 days prior to enrollment in this study or who are planning to receive any vaccine up to 14 days after the second vaccination.
11. Individuals with known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular injection.
12. Individuals who received any blood/plasma products or immunoglobulins within 60 days prior to Day 1 or plan to receive it during the study period.
13. Individuals with any condition that, in the opinion of the investigator, may increase the risk of study participation or interfere with the assessment of the primary study objectives.
14. Individuals with fever >37.8°C (irrespective of method), or any acute illness at baseline (Day 1) or within 3 days of randomization.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Vincent Mwangi, MD; +1 847-691-8580; Vincent.mwangi@cloverbiopharma.com

Contact: Pilar Rubio, MD; +57 314-857-0960; Pilar.Rubio@cloverbiopharma.com

• Listed Location Countries: Belgium, Brazil, Colombia, Philippines, South Africa
• Removed Location Countries: Dominican Republic, Germany, Nepal, Panama, Poland

Administrative Information

• NCT Number: NCT04672395
• Other Study ID Numbers: CLO-SCB-2019-003
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Clover Biopharmaceuticals AUS Pty Ltd
• Original Responsible Party: Same as current
• Current Study Sponsor: Clover Biopharmaceuticals AUS Pty Ltd
• Original Study Sponsor: Same as current

Collaborators

• Coalition for Epidemic Preparedness Innovations
• International Vaccine Institute

Investigators

• Study Chair: Igor Smolenov, MD, PhD; Clover Biopharmaceuticals AUS Pty Ltd

• PRS Account: Clover Biopharmaceuticals AUS Pty Ltd
• Verification Date: February 2022