Safety and Immunogenicity of SCB-2019 in Children <18 Years of Age

A Randomized, Controlled, Dose-finding, Observer-blind, Phase 2/3 Study to Evaluate the Safety, Reactogenicity and Immunogenicity of CpG/Alum-adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccines (SCB-2019 Vaccine) in Children <18 Years of Age

This is a phase 2/3, randomized, controlled study to assess the reactogenicity, safety and immunogenicity of adjuvanted recombinant SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019), when administered as 2-dose vaccination series in children below 18 years of age.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19
• Intervention / Treatment: Biological: Candidate vaccine, SCB-2019

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

Contacts and Locations

• Study Contact: Name: Margaret Khin, MD; Email: Margaret.Khin@cloverbiopharma.com

Study Locations

• Colombia
  • Barranquilla, Colombia, 080020
    • Clinica de la Costa Ltda
    • Contact: Maria Alexandra Castañeda, M.Sc; Phone Number: +5753736200; Email: lbrochado@clinicadelacosta.co
    • Contact: Daniela Higgins Molina, Physician
    • Principal Investigator: Dr. Leonardo Fabio Brochado Fontalvo, M.D.
  • Cali, Colombia
    • Centro de Estudios en Infectología Pediátrica S.A.S. - CEIP S.A.S.
    • Contact: Hilda Giraldo Orjuela; Phone Number: +5724860220X1113; Email: pio.lopez@ceiponline.org
    • Contact: Julio Cesar Rengifo
    • Principal Investigator: Dr. Pio Lopez, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female <18 years of age. Participants will be stratified into different age cohorts (≥12 to < 18 years, ≥5 to < 12 years, ≥2 to < 5 years, and < 2 years of age) based on the age on the day of inclusion.
• Individuals and their legally authorized representative (LAR) are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests and other study procedures.
• Individuals are willing and able to give an assent (if applicable) and their LARs are willing and able to give informed consent on their behalf, prior to screening
• Healthy participants (phase 2 and phase 3) or participants with pre-existing medical conditions who are in a stable medical condition (phase 2)
• For infants (<1-year-old) - born at full term (gestational age ≥37 weeks) and with a normal birth weight (≥2500 grams).
• Female participants of childbearing potential may be enrolled in the study, if the participant has practiced highly effective contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination and has agreed to continue adequate contraception for 3 months after the last vaccination

Exclusion Criteria:

• Individuals with fever >38.0°C [≥ 100.4°F] (irrespective of method used), or any acute illness at baseline (Day 1) or within 3 days prior to randomization.
• Individuals with laboratory-confirmed SARS-CoV-2 infection [as defined by Rapid COVID Antigen Test or an equivalent at Day 1] or with history of laboratory-confirmed/medically-diagnosed COVID-19 (for phase 2 participants only).
• Individuals who have received an investigational or licensed COVID-19 vaccine prior to Day 1, or plan to receive an investigational or licensed COVID-19 vaccine during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease [e.g., malignancy, human immunodeficiency virus (HIV) infection] or immunosuppressive/cytotoxic therapy (e.g., systemic corticosteroids, medications used for cancer chemotherapy, organ transplantation or to treat autoimmune disorders) within 3 months prior to Day 1. Inhaled, intranasal, topical steroids as well as a single dose of systemic steroids, are allowed.
• Individuals with any progressive or severe neurologic disorder, seizure disorder (including febrile seizures) or history of Guillain-Barré syndrome.
• Individuals who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or during the study period.
• Individuals who have a history of severe adverse reaction associated with a vaccine or severe allergic reaction
• Individuals who have received any other investigational product within 30 days prior to Day 1 or intend to participate in another clinical study at any time during the conduct of this study.
• 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 28 days after the second (phase 2) or third (phase 3) vaccination.
• Individuals with known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular injection
• Administration of intravenous immunoglobulins and/or any blood products within 3 months prior to enrollment or planned administration during the study period
• Individuals with any condition that, in the opinion of the investigator, would interfere with the primary study objectives or pose additional risk to the participant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

21

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCB-2019/SCB-2019/placebo, 12 to < 18 yrs; Day 1 and 22: SCB-2019, Day 43: placebo	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Placebo/SCB-2019/SCB-2019, 12 to < 18 years; Day 1: placebo, Day 22 and 43: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: SCB-2019/placebo/SCB-2019, 12 to < 18 years; Day 1 and 43: SCB-2019, Day 22: placebo	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Low dose SCB-2019, 5 to < 12 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Mid dose SCB-2019, 5 to < 12 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: High dose SCB-2019, 5 to < 12 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: SCB-2019/SCB-2019/placebo, 5 to < 12 yrs; Day 1 and 22: SCB-2019, Day 43: placebo	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Placebo/SCB-2019/SCB-2019, 5 to < 12 years; Day 1: placebo, Day 22 and 43: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: SCB-2019/placebo/SCB-2019, 5 to < 12 years; Day 1 and 43: SCB-2019, Day 22: placebo	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Low dose SCB-2019, 2 to < 5 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Mid dose SCB-2019, 2 to < 5 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: High dose SCB-2019, 2 to < 5 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: SCB-2019/SCB-2019/placebo, 2 to < 5 yrs; Day 1 and 22: SCB-2019, Day 43: placebo	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Placebo/SCB-2019/SCB-2019, 2 to < 5 years; Day 1: placebo, Day 22 and 43: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: SCB-2019/placebo/SCB-2019, 2 to < 5 years; Day 1 and 43: SCB-2019, Day 22: placebo	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Low dose SCB-2019, birth to < 2 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Mid dose SCB-2019, birth to < 2 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: High dose SCB-2019, birth to < 2 years; Day 1 and 22: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: SCB-2019/SCB-2019/placebo, birth to < 2 yrs; Day 1 and 22: SCB-2019, Day 43: placebo	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: Placebo/SCB-2019/SCB-2019, birth to < 2 years; Day 1: placebo, Day 22 and 43: SCB-2019	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19
Experimental: SCB-2019/placebo/SCB-2019, birth to < 2 years; Day 1 and 43: SCB-2019, Day 22: placebo	Biological: Candidate vaccine, SCB-2019; a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2, select optimal dose level of SCB-2019 vaccine by age cohort (5-11 years, 2-4 years, and < 2 years), based on safety	Proportion of subjects with solicited local and systemic adverse events	7 days after dose 1 (Day 1-7)
Phase 2, select optimal dose level of SCB-2019 vaccine by age cohort (5-11 years, 2-4 years, and < 2 years), based on safety	Proportion of subjects with solicited local and systemic adverse events	7 days after dose 2 (Day 22-28)
Phase 2, select optimal dose level of SCB-2019 vaccine in phase 2 by age cohort (5-11 years, 2-4 years, and < 2 years), based on immunogenicity	Geometric mean titer (GMT) of SARS-CoV-2 neutralising antibody (nAb)	Day 36
Phase 3, non-inferiority (GMT) of SARS-CoV-2 nAb titers of SCB-2019 vaccine when given to participants 5 to < 12 years as compared to young adults (18 to < 25 years)	GMT of SARS-CoV-2 nAb after 2 doses of SCB-2019 vaccine in participants 5 to 12 years over GMT in participants 18 to < 25 years from CLO-SCB-2019-003 study	21/15 days after second SCB-2019 dose
Phase 3, non-inferiority (GMT) of SARS-CoV-2 nAb titers of SCB-2019 vaccine when given to participants 2 to < 5 years as compared to young adults (18 to < 25 years)	GMT of SARS-CoV-2 nAb after 2 doses of SCB-2019 vaccine in participants 2 to 5 years over GMT in participants 18 to < 25 years from CLO-SCB-2019-003 study	21/15 days after second SCB-2019 dose
Phase 3, non-inferiority (GMT) of SARS-CoV-2 nAb titers of SCB-2019 vaccine when given to participants birth to < 2 years as compared to young adults (18 to < 25 years)	GMT of SARS-CoV-2 nAb after 2 doses of SCB-2019 vaccine in participants birth to 2 years over GMT in participants 18 to < 25 years from CLO-SCB-2019-003 study	21/15 days after second SCB-2019 dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 3, non-inferiority (SCR difference) of SARS-CoV-2 nAb titers of SCB-2019 vaccine when given to participants 5 to < 12 years as compared to young adults (18 to < 25 years)	Proportion of participants achieving seroconversion for SARS-CoV-2 nAb after 2 doses of SCB-2019 vaccine in participants 5 to < 12 years minus proportion in participants 18 to < 25 years from CLO-SCB-2019-003 study	21/15 days after second SCB-2019 dose
Phase 3, non-inferiority (SCR difference) of SARS-CoV-2 nAb titers of SCB-2019 vaccine when given to participants 2 to < 5 years as compared to young adults (18 to < 25 years)	Proportion of participants achieving seroconversion for SARS-CoV-2 nAb after 2 doses of SCB-2019 vaccine in participants 2 to < 5 years minus proportion in participants 18 to < 25 years from CLO-SCB-2019-003 study	21/15 days after second SCB-2019 dose
Phase 3, non-inferiority (SCR difference) of SARS-CoV-2 nAb titers of SCB-2019 vaccine when given to participants birth to < 2 years as compared to young adults (18 to < 25 years)	Proportion of participants achieving seroconversion for SARS-CoV-2 nAb after 2 doses of SCB-2019 vaccine in participants birth to < 2 years minus proportion in participants 18 to < 25 years from CLO-SCB-2019-003 study	21/15 days after second SCB-2019 dose
In phase 2 and 3, GMT of SARS-CoV-2 nAb		Day 1 , 22 and 36 (phase 2) and Day 1, 43, 64, 226 and 410 (phase 3)
In phase 2 and 3, proportion of participants achieving seroconversion for SARS-CoV-2 nAb		Day 22 and 36 (phase 2) and Day 43, 64, 226 and 410 (phase 3)
In phase 2 and 3, GMFR in SARS-CoV-2 nAb		Day 22 and 36 (phase 2) and Day 43, 64, 226 and 410 (phase 3)
In phase 2 and 3, proportion of participants with SARS-CoV-2 nAb above a certain threshold		Day 1 , 22 and 36 (phase 2) and Day 1, 43, 64, 226 and 410 (phase 3)
In phase 2 and 3, GMT of SCB-2019 Binding Antibody		Day 1 , 22 and 36 (phase 2) and Day 1, 43, 64, 226 and 410 (phase 3)
In phase 2 and 3, proportion of participants achieving seroconversion for SCB-2019 binding antibody		Day 22 and 36 (phase 2) and Day 43, 64, 226 and 410 (phase 3)
In phase 2 and 3, GMFR of SCB-2019 binding antibody		Day 22 and 36 (phase 2) and Day 43, 64, 226 and 410 (phase 3)
In phase 2 and 3, proportion of participants with SCB-2019 binding antibody above a certain threshold		Day 1 , 22 and 36 (phase 2) and Day 1, 43, 64, 226 and 410 (phase 3)
In phase 3, reactogenicity of the vaccine as indicated by the occurrence of solicited local and systemic reactions	In phase 3, proportion of participants with local and systemic AEs	7 days after dose 1 (Day 1-7), dose 2 (Day 22-Day 28) and Dose 3 (Day 43-49)
Phase 2 and 3, safety of the vaccine in terms of occurrence of unsolicited adverse events	Proportion of subjects with unsolicited adverse events	Up to 21 days after the last vaccination
Phase 2 and 3, safety of the vaccine in terms of occurrence of MAAEs, SAEs, adverse events leading to discontinuation from study, and AESIs.	Proportion of participants with any adverse events in this category.	During the entire study period

Collaborators and Investigators

• Sponsor: Clover Biopharmaceuticals AUS Pty Ltd

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2022
• Primary Completion (Actual): December 15, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: December 23, 2021
• First Submitted That Met QC Criteria: January 11, 2022
• First Posted (Actual): January 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: CLO-SCB-2019-007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No