SCB-2019 as COVID-19 Vaccine

• ClinicalTrials.gov Identifier: NCT04405908
• Recruitment Status: Active, not recruiting
• First Posted: May 28, 2020
• Last Update Posted: January 12, 2021
• Sponsor: Clover Biopharmaceuticals AUS Pty Ltd
• Information provided by (Responsible Party): Clover Biopharmaceuticals AUS Pty Ltd

Tracking Information

• First Submitted Date: May 25, 2020
• First Posted Date: May 28, 2020
• Last Update Posted Date: January 12, 2021
• Actual Study Start Date: June 19, 2020
• Actual Primary Completion Date: October 16, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 28, 2020)

• Incidence of solicited adverse events (AEs) after vaccination [ Time Frame: 7 days after the first or second vaccination. ]
• Incidence of unsolicited AEs after vaccination [ Time Frame: Day 1 to Day 50 ]
• Immunogenicity(Anti-SCB-2019 Antibody Titers) [ Time Frame: Day 1 to Day 184 ]
  Geometric mean titer (GMT). Geometric mean ratio (GMR). Seroconversion rate (SCR).
• Incidence of serious AEs (SAEs) and adverse events of special interest (AESIs) [ Time Frame: Day 1 to Day 184 ]

Original Primary Outcome Measures (submitted: May 25, 2020)

• Incidence of solicited adverse events (AEs) after vaccination [ Time Frame: 7 days after the first or second vaccination. ]
• Incidence of unsolicited AEs after vaccination [ Time Frame: Day 1 to Day 50 ]
• Immunogenicity(Anti-SCB-2019 Antibody Titers) [ Time Frame: Day 1 to Day 184 ]
• Incidence of serious AEs (SAEs) and adverse events of special interest (AESIs) [ Time Frame: Day 1 to Day 184 ]

Current Secondary Outcome Measures (submitted: May 28, 2020)

• Immunogenicity( serum anti SARS-CoV-2 neutralizing antibody titers (ACE2 receptor-based) ) [ Time Frame: Day 1 to Day 184 ]
  Geometric mean titer (GMT). Geometric mean ratio (GMR). Seroconversion rate (SCR).
• Immunogenicity(serum anti SARS-CoV-2 neutralizing antibody titers (cell based) ) [ Time Frame: Day 1 to Day 184 ]
  Geometric mean titer (GMT). Geometric mean ratio (GMR). Seroconversion rate (SCR).
• Immunogenicity(serum anti SARS-CoV-2 whole virus antibody titers) [ Time Frame: Day 1 to Day 184 ]
  Geometric mean titer (GMT). Geometric mean ratio (GMR). Seroconversion rate (SCR).
• Antibody kinetics of each SCB 2019 vaccine formulation after first and second doses [ Time Frame: Day 1 to Day 184 ]
  Geometric mean titer (GMT). Geometric mean ratio (GMR). Seroconversion rate (SCR).

Original Secondary Outcome Measures (submitted: May 25, 2020)

• Immunogenicity( serum anti SARS-CoV-2 neutralizing antibody titers (ACE2 receptor-based) ) [ Time Frame: Day 1 to Day 184 ]
• Immunogenicity(serum anti SARS-CoV-2 neutralizing antibody titers (cell based) ) [ Time Frame: Day 1 to Day 184 ]
• Immunogenicity(serum anti SARS-CoV-2 whole virus antibody titers) [ Time Frame: Day 1 to Day 184 ]
• Antibody kinetics of each SCB 2019 vaccine formulation after first and second doses [ Time Frame: Day 1 to Day 184 ]

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

Descriptive Information

• Brief Title: SCB-2019 as COVID-19 Vaccine
• Official Title: A Phase 1, Randomized, Double-blind, Placebo-controlled, First-in-human Study to Evaluate the Safety and Immunogenicity of SCB 2019, a Recombinant SARS-CoV-2 Trimeric S Protein Subunit Vaccine for COVID-19 in Healthy Volunteers.
• Brief Summary: This is a randomized, double blind, placebo controlled, first-in-human (FIH) study to assess safety, reactogenicity, and immunogenicity of SCB-2019 at multiple dose levels, administered as 2 injections IM in healthy subjects. Each study vaccine dose level will be evaluated with and without adjuvant.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: COVID-19

Intervention

• Biological: SCB-2019
  SCB-2019 intramuscular vaccinations at 3 µg up to 30 µg twice (on Day 1 and Day 22).
• Biological: SCB-2019 with AS03 adjuvant
  SCB-2019 intramuscular vaccinations at 3 µg up to 30 µg twice (on Day 1 and Day 22), and administered with AS03 adjuvant.
• Biological: SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant
  SCB-2019 intramuscular vaccinations at 3 µg up to 30 µg twice (on Day 1 and Day 22), and administered with CpG 1018 plus Alum adjuvant.

Study Arms

• Active Comparator: Adult Group 1
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 3 µg.
  Intervention: Biological: SCB-2019
• Active Comparator: Adult Group 2
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 3 µg with AS03 adjuvant.
  Intervention: Biological: SCB-2019 with AS03 adjuvant
• Active Comparator: Adult Group 3
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 3 µg with CpG 1018 plus Alum adjuvant.
  Intervention: Biological: SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant
• Active Comparator: Adult Group 4
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 9 µg .
  Intervention: Biological: SCB-2019
• Active Comparator: Adult Group 5
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 9 µg with AS03 adjuvant.
  Intervention: Biological: SCB-2019 with AS03 adjuvant
• Active Comparator: Adult Group 6
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 9 µg with CpG 1018 plus Alum adjuvant.
  Intervention: Biological: SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant
• Active Comparator: Adult Group 7
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 30 µg .
  Intervention: Biological: SCB-2019
• Active Comparator: Adult Group 8
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 30 µg with AS03 adjuvant.
  Intervention: Biological: SCB-2019 with AS03 adjuvant
• Active Comparator: Adult Group 9
  Adult healthy subjects (18 to 54 years of age, inclusive) receive SCB-2019 30 µg with CpG 1018 plus Alum adjuvant.
  Intervention: Biological: SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant
• Active Comparator: Elderly Group 10
  Elderly healthy subjects (55 to 75 years of age, inclusive) receive SCB-2019 3 µg with AS03 adjuvant.
  Intervention: Biological: SCB-2019 with AS03 adjuvant
• Active Comparator: Elderly Group 11
  Elderly healthy subjects (55 to 75 years of age, inclusive) receive SCB-2019 3 µg with CpG 1018 plus Alum adjuvant.
  Intervention: Biological: SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant
• Active Comparator: Elderly Group 12
  Elderly healthy subjects (55 to 75 years of age, inclusive) receive SCB-2019 9 µg with AS03 adjuvant.
  Intervention: Biological: SCB-2019 with AS03 adjuvant
• Active Comparator: Elderly Group 13
  Elderly healthy subjects (55 to 75 years of age, inclusive) receive SCB-2019 9 µg with CpG 1018 plus Alum adjuvant.
  Intervention: Biological: SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant
• Active Comparator: Elderly Group 14
  Elderly healthy subjects (55 to 75 years of age, inclusive) receive SCB-2019 30 µg with AS03 adjuvant.
  Intervention: Biological: SCB-2019 with AS03 adjuvant
• Active Comparator: Elderly Group 15
  Elderly healthy subjects (55 to 75 years of age, inclusive) receive SCB-2019 30 µg with CpG 1018 plus Alum adjuvant.
  Intervention: Biological: SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant

• Publications *: Richmond P, Hatchuel L, Dong M, Ma B, Hu B, Smolenov I, Li P, Liang P, Han HH, Liang J, Clemens R. Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial. Lancet. 2021 Feb 20;397(10275):682-694. doi: 10.1016/S0140-6736(21)00241-5. Epub 2021 Jan 29.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 25, 2020): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 25, 2021
• Actual Primary Completion Date: October 16, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Healthy adult male or females, ≥18 years of age at Screening:

   1. For the adult group: 18 to 54 years, inclusive, and
   2. For the elderly group: 55 to 75 years, inclusive.
2. Individuals who are willing and able to give an informed consent, prior to Screening.
3. Individuals who are able to comply with study requirements.

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

   1. Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test prior to each vaccination. They must be using a highly effective licensed method of birth control for 30 days prior to the first dose of the study vaccine/placebo and must agree to continue such precautions during the study until 60 days after the second dose of the study vaccine/placebo.
   2. Women not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal (no menses for 12 months and follicle-stimulating hormone [FSH] in the postmenopausal range).
   3. Male subjects must agree to employ acceptable contraception from the day of first dose of the study vaccine/placebo until 90 days after the second dose of the study vaccine/placebo and also refrain from donating sperm during this period.
5. General good health based on medical history, physical examination, cardiac health evaluation, and clinical laboratory evaluations. Participants in the elderly population who have medically stable, well-controlled co-morbidities may be enrolled at the discretion of the Investigator.

All clinical laboratory values should be within normal reference ranges unless confirmed by Investigator or delegate as not clinically significant. One repeat evaluation of electrocardiogram (ECG), and clinical laboratory tests will be permitted, at the discretion of the Investigator.

Exclusion Criteria:

1. Individuals with any positive test for SARS CoV 2 infection, including but not limited to RT-PCR, at Screening.
2. Individuals with positive serology test results for SARS CoV 2 at Screening.
3. Individuals with behavioral or cognitive impairment in the opinion of the Investigator.
4. Individuals with any progressive or severe neurologic disorder, seizure disorder, or history of Guillian-Barré syndrome.
5. Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study.

6. Individuals with known or suspected impairment of the immune system, such as:

   1. Use of systemic (oral or parenteral) corticosteroids for ≥14 consecutive days within 60 days prior to Day 1. Use of inhaled, intranasal, or topical corticosteroids is allowed.Note: Systemic (oral or parenteral) corticosteroids are also prohibited for 3 weeks after the second dose of the study vaccine/placebo.
   2. Receipt of cancer chemotherapy within 5 years prior to Day 1.
   3. Receipt of immunostimulants or immunosuppressants within 60 days prior to Day 1.
   4. Known HIV or acquired immune deficiency syndrome (AIDS).
   5. Subjects with active or prior documented autoimmune disorder (such as potential immune-mediated diseases [pIMDs]).
   6. Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Day 1 or planned during the full length of the study.
7. Positive serology test results for hepatitis C virus antibody, HIV antibody, and/or hepatitis B virus surface antigen at Screening.
8. Individuals who are pregnant or breastfeeding. Female subjects of childbearing potential must have a negative pregnancy test prior to administration of the study vaccine/placebo.
9. Individuals who are allergic to any of the study vaccine/placebo components as outlined in the current SCB 2019 IB.
10. Individuals who have had a malignancy (excluding nonmelanotic skin cancer) or lymphoproliferative disorder within the past 5 years from the date of first administration of the study vaccine/placebo (Day 1).
11. 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.
12. Individuals with a body temperature ≥38.0 °C (≥100.4 °F) or any acute illness within 3 days of intended study vaccination.
13. Individuals who have a previous confirmed or suspected illness caused by coronaviruses, SARS-CoV 1, SARS-CoV-2, and Middle East Respiratory Syndrome (MERS)-CoV.
14. Individuals who have received any prior vaccine against a coronavirus, including but not limited to SARS-CoV, SARS-CoV-2, MERS-CoV.
15. Individuals who have received any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who are planning to receive any vaccine within 28 days (before or after) the study vaccine/placebos, with the exception of the seasonal influenza vaccine.
16. Presence of uncontrolled chronic pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic or metabolic (including diabetes mellitus) disorders, which would include the potential subject in a high-risk category for SARS CoV 2 infection and/or its complications.
17. Individuals with known bleeding diathesis.
18. Individuals with a body mass index <18.5 kg/m2 or >35.0 kg/m2.
19. Individuals with a history of drug or alcohol abuse within the past 2 years.
20. Individuals with a history of anaphylaxis or angioedema including but not limited to history of anaphylaxis after any vaccine.
21. Individuals with any condition that, in the opinion of the Investigator, would interfere with the primary study objectives or pose additional subject risk.
22. Individuals who are research staff involved with the clinical study or family/household members of research staff.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT04405908
• Other Study ID Numbers: CLO-SCB-2019-001
• Has Data Monitoring Committee: Not Provided

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
• Responsible Party: Clover Biopharmaceuticals AUS Pty Ltd
• Study Sponsor: Clover Biopharmaceuticals AUS Pty Ltd
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Clover Biopharmaceuticals AUS Pty Ltd
• Verification Date: January 2021