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

COVID-19 Clinical Trial

— SCB-2019  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04672395
• Other study ID #: CLO-SCB-2019-003
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 24, 2021
• Est. completion date: April 23, 2023

Study information

• Verified date: June 2023
• Source: Clover Biopharmaceuticals AUS Pty Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31454
• Est. completion date: April 23, 2023
• Est. primary completion date: September 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years and older

Eligibility

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. 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

4. 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.

5. 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.

6. 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.

7. Applicable for HIV-positive individuals only if:

They are medically stable at screening, as determined by the investigator, and free of opportunistic infections in the 1 year prior to first study vaccination, and They have an HIV-1 viral load <1000 copies/mL within 45 days of randomization in the study, and They are receiving highly active antiretroviral therapy (HAART) for at least 3 months before screening. Changes in antiretroviral dosage within 3 months of entering the study are allowed, as are exchanges in pharmacological formulations.

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) in the 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).

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.

Related Conditions & MeSH terms

• 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
• Placebo; 0.9% saline
Group 2: Participants will receive 1 IM injection of SCB-2019-matching placebo on Day 1 and on Day 22
• SCB-2019 vaccine
Participants will receive 1 IM injection of 30 microgram (ug) SCB-2019 with CpG 1018/alum adjuvant
• 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

Locations

Country	Name	City	State
Belgium	Anima	Alken
Belgium	Hôspital Erasme	Bruxelles
Belgium	Private Practice RESPISOM Namur	Namur
Brazil	CPCLIN - Centro de Pesquisas Clínicas de Natal	Natal	Rio Grande Do Norte
Brazil	Instituto Atena de Pesquisa Clinica	Natal	Rio Grande Do Norte
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto D'OR de Pesquisa e Ensino	Rio de Janeiro	Rio Do Janeiro
Brazil	Hospital da Universidade Federal de Santa Maria CEP/UFSM	Santa Maria	Rio Grande Do Sul
Colombia	Centro de Atención e investigación Médica S.A.S, CAIMED S.A.S - sede, Acacias	Acacías
Colombia	Centro de Atención e investigación Médica S.A.S, CAIMED S.A.S - sede Aguazul	Aguazul
Colombia	Clínica de la Costa Ltda	Barranquilla
Colombia	Fundación Hospital Universitario del Norte	Barranquilla
Colombia	Centro de Atención e investigación Médica S.A.S, CAIMED S.A.S - sede, Bogotá D.C.	Bogotá
Colombia	Policlinico Social del Norte	Bogotá
Colombia	Centro de Estudios en Infectología Pediátrica S.A.S. - CEIP S.A.S.	Cali
Colombia	IPS Médicos Internistas de Caldas SAS	Manizales
Colombia	Centro de Atención e investigación Médica S.A.S, CAIMED S.A.S - sede, Yopal	Yopal
Philippines	De La Salle Medical and Health Sciences Institute	Dasmariñas	Cavite
Philippines	Las Pinas Doctors Hospital	Las Piñas
Philippines	Tropical Disease Foundation	Makati
Philippines	Manila Doctors Hospital	Manila
Philippines	Asian Hospital and Medical Center	Muntinlupa
Philippines	University of the Philippines Manila - Philippine General Hospital	Pasay
Philippines	FEU-NRMF Medical Center	Quezon City
Philippines	UERM Memorial Medical Center	Quezon City
Philippines	University of the East Ramon Magsaysay Memorial Medical Center	Quezon City
Philippines	St. Luke's Medical Center	Taguig
South Africa	Wits Clinical Research	Johannesburg	Gauteng
South Africa	DJW Research	Krugersdorp	Gauteng
South Africa	Dr JM Engelbrecht Trial Site	Somerset West	Western Cape
South Africa	Soweto Clinical Trials Centre	Soweto	Gauteng

Sponsors (3)

Lead Sponsor	Collaborator
Clover Biopharmaceuticals AUS Pty Ltd	Coalition for Epidemic Preparedness Innovations, International Vaccine Institute

Countries where clinical trial is conducted

Belgium,  Brazil,  Colombia,  Philippines,  South Africa, 

References & Publications (8)

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.

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.

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.

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. — View Citation

Maurer W, Bretz F. Multiple testing in group sequential trials using graphical approaches. Stat Biopharm Res 2013;5(4):311-20.

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. — View Citation

Ruggeberg 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, Makela 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. doi: 10.1016/j.vaccine.2007.02.064. Epub 2007 Mar 12. No abstract available. — View Citation

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with a First Occurrence of COVID-19 of Any Severity Starting 14 Days after Second Dose of SCB-2019		Day 36 up to Day 389 (1 year after second dose)
Primary	Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)		Up to Day 8 (7 days after first dose) and up to Day 29 (7 days after second dose)
Primary	Number of Participants with Unsolicited AEs		Up to Day 43 (21 days after each dose)
Primary	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)		Up to Day 389 (1 year after second dose)
Primary	Non-inferiority of the neutralizing titers after third dose compared to the neutralizing titers after second dose		14 days after third dose
Primary	Non-inferiority of the neutralising titers in adolescents versus young adults.		14 days after second dose
Secondary	Number of Participants with a First Occurrence of Moderate-to-Severe COVID-19 Starting 14 Days after Second Dose of SCB-2019		Day 36 up to Day 389 (1 year after second dose)
Secondary	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		Day 36 up to Day 389 (1 year after second dose)
Secondary	Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of SCB-2019 or Placebo		Day 36 up to Day 389 (1 year after second dose)
Secondary	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		Day 36 up to Day 389 (1 year after second dose)
Secondary	Burden of Disease Score of COVID-19 or SARS-CoV-2 Infection Cases Starting 14 Days after Second Dose of SCB-2019 or Placebo		Day 36 up to Day 389 (1 year after second dose)
Secondary	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		Day 36 up to Day 389 (1 year after second dose)
Secondary	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		Day 36 up to Day 389 (1 year after second dose)
Secondary	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		Day 36 up to Day 389 (1 year after second dose)
Secondary	Number of Participants with a First Occurrence of COVID-19 Starting 14 days after First Dose of SCB-2019 or Placebo		Day 15 up to Day 22
Secondary	Number of Participants with a First Occurrence of COVID-19 of Any Severity caused by SARS-CoV-2 variants of concern starting 14 days after Second Dose		Day 36 up to Day 389 (1 year after second dose)
Secondary	Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Number of Participants with Seroconversion for SARS-CoV-2 Specific nAb		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Geometric Mean Titer (GMT) of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Number of Participants with Seroconversion for of SARS-CoV-2 antibodies competing for binding of S protein to the human ACE2 receptor		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Geometric Mean Titer (GMT) of SCB-2019 binding antibody		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Geometric Mean Fold Rise (GMFR) of SCB-2019 binding antibody		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Number of Participants with Seroconversion for SCB-2019 binding antibody		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Geometric Mean Titer (GMT) of Trimer-Tag binding antibody		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Geometric Mean Fold Rise (GMFR) of Trimer-Tag binding antibody		Day 1, Day 22, Day 35, Day 205, and Day 389
Secondary	Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)		Up to 7 days after booster dose
Secondary	Number of Participants with Unsolicited AEs		Up to 21 days after booster dose
Secondary	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)		Up to 6 months after booster dose
Secondary	Geometric Mean Titer (GMT) of SARS-CoV-2 Specific nAb		Day 1A, Day 15A (15 days after booster), and Day 389A (6 months after booster)
Secondary	Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb		Day 1A, Day 15A (15 days after booster), and Day 389A (6 months after booster)
Secondary	Number of Participants with Seroconversion for SARS-CoV-2 Specific nAb		Day 1A, Day 15A (15 days after booster), and Day 389A (6 months after booster)
Secondary	Geometric Mean Titer (GMT) of SCB-2019 binding antibody		Day 1A, Day 15A (15 days after booster), and Day 389A (6 months after booster)
Secondary	Geometric Mean Fold Rise (GMFR) of SCB-2019 binding antibody		Day 1A, Day 15A (15 days after booster), and Day 389A (6 months after booster)
Secondary	Number of Participants with Seroconversion for SCB-2019 binding antibody		Day 1A, Day 15A (15 days after booster), and Day 389A (6 months after booster)