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)

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ClinicalTrials.gov Identifier: NCT04672395

Recruitment Status : Not yet recruiting

First Posted : December 17, 2020

Last Update Posted : February 9, 2021

See Contacts and Locations

Sponsor:

Collaborators:

Coalition for Epidemic Preparedness Innovations

International Vaccine Institute

Information provided by (Responsible Party):

Clover Biopharmaceuticals AUS Pty Ltd

Tracking Information

First Submitted Date ^ICMJE

December 16, 2020

First Posted Date ^ICMJE

December 17, 2020

Last Update Posted Date

February 9, 2021

Estimated Study Start Date ^ICMJE

March 2021

Estimated Primary Completion Date

July 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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) ]

Original Primary Outcome Measures ^ICMJE

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) ]

Change History

Current Secondary Outcome Measures ^ICMJE

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 ]

Original Secondary Outcome Measures ^ICMJE

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 ^ICMJE

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 ^ICMJE

A Double-Blind, Randomized, Controlled, Phase 2/3 Study to Evaluate the Efficacy, Immunogenicity, and Safety of SCB 2019, a Recombinant SARS-CoV-2 Trimeric S Protein Subunit Vaccine for the Prevention of COVID-19 in Participants Aged 18 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 adult subjects 18 years of age and above.

Detailed Description

This study will assess the efficacy against COVID-19 and SARS-CoV-2 infection, 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. A safe and effective vaccine for COVID-19 prevention would have significant public health impact.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2
Phase 3

Study Design ^ICMJE

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

Each subject will receive 2 doses of their assigned treatment, on Days 1 and 22. The treatment will be administered IM in the deltoid region of the upper arm.

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

Condition ^ICMJE

COVID-19

Intervention ^ICMJE

Biological: CpG 1018/Alum-adjuvanted SCB-2019 vaccine
Group 1: Participants will receive 1 intramuscular (IM) injection of 30 microgram (ug) SCB-2019 with CpG 1018/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

Study Arms ^ICMJE

Experimental: Group 1
CpG 1018/Alum-adjuvanted SCB-2019 vaccine

Intervention: Biological: CpG 1018/Alum-adjuvanted SCB-2019 vaccine
Placebo Comparator: Group 2
0.9% sodium chloride

Intervention: Biological: Placebo; 0.9% saline

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.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

22000

Original Estimated Enrollment ^ICMJE

34000

Estimated Study Completion Date ^ICMJE

July 2022

Estimated Primary Completion Date

July 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Male or females ≥18 years of age, inclusive.
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.
Healthy adults or adults with pre-existing medical conditions who are in stable condition.

A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrolment
Female subjects are eligible to participate in the study if not pregnant, not breastfeeding, and at least 1 of the following criteria apply:

• Women of childbearing potential (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.
Individuals (or their legally acceptable representative based on local regulations) willing and able to give an informed consent, prior to screening

Exclusion Criteria:

Individuals with laboratory-confirmed SARS-CoV-2 infection (e.g., a positive result for the Rapid COVID-19 antigen test) or a known history of SARS-CoV-2 infection.
Individuals with behavioral or cognitive impairment (including drug and alcohol abuse) in the opinion of the Investigator.
Individuals with any progressive or severe neurologic disorder, seizure disorder, or history of Guillian-Barré syndrome.
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.
Individuals who are pregnant, or breastfeeding, or planning to become pregnant during the study period.
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
Individuals who have a history of malignancy within 1 year before screening
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.
Individuals who have received previous vaccination with any coronavirus vaccine.
Individuals who have received any other licensed vaccines within 28 days prior to enrollment in this study or who are planning to receive any vaccine up to 14 days after the second vaccination.
Individuals with known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular injection.
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.
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
Individuals with fever >37.8°C (≥100.04°F; irrespective of method), or any acute illness at baseline (Day 1) or within 3 days of randomization.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Yes

Contacts ^ICMJE

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 ^ICMJE

Belgium, Brazil, Colombia, Dominican Republic, Germany, Nepal, Panama, Philippines, Poland, South Africa

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04672395

Other Study ID Numbers ^ICMJE

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 ^ICMJE

Not Provided

Responsible Party

Clover Biopharmaceuticals AUS Pty Ltd

Study Sponsor ^ICMJE

Clover Biopharmaceuticals AUS Pty Ltd

Collaborators ^ICMJE

Coalition for Epidemic Preparedness Innovations
International Vaccine Institute

Investigators ^ICMJE

Study Chair:

Igor Smolenov, MD, PhD

Clover Biopharmaceuticals AUS Pty Ltd

PRS Account

Clover Biopharmaceuticals AUS Pty Ltd

Verification Date

February 2021

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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