Safety & Immunogenicity of Booster SARS-CoV-2 Vaccine (Vero Cell)

A Phase II Non-Randomized Open Labelled Clinical Trial to Evaluate the Safety & Immunogenicity of SARS-COV-2 Vaccine (Vero Cell) Inactivated as A Booster Dose

The 2019 Coronavirus disease outbreak (COVID-19) was first reported at the end of 2019 in Wuhan China as a severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection. In less than a year, SARS-CoV-2 infection has become a pandemic and spread to almost all countries in the world, including Indonesia. World Health Organization data states that there are 4,240,479 confirmed cases of SARS-CoV-2 in Indonesia until 25 October 2021 with a death rate of 143,235 (WHO, 2021a).

The Indonesian National Agency of Drug and Food Control (NA-DFC) has issued an Emergency Use Authorization for several SARS-COV-2 Vaccines, including the SARS-CoV-2 vaccine (Vero cell) inactivated produced by Sinopharm (BPOM, 2021). Clinical data that the actual immune responses decrease after several months are continuously being reported (Marmot et al., 2021), and the decrease of vaccine efficacy due to the appearance of variants is also known (Abu-Raddad et al., 2021; Lopez Bernal et al., 2021). These potential risks suggest the need for a booster dose or periodic booster doses of the SARS-COV-2 Vaccine. In fact, there is a study result given several months after vaccination, which leads to the generation of a higher immune responses (Pan H et al., 2021). Booster dose of SARS-COV-2 Vaccine will either induce a high level of antibody responses against original strain, or enhance the broadly formed T cell immunity regardless of mutant strain to improve individual protection.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: SARS-COV-2 Vaccine (Vero Cell-Sinopharm) Inactivated

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Prenali Dwisthi Sattwika; Phone Number: +62 274-560-455; Email: boost.vctrial@gmail.com
• Study Contact Backup: Name: Jarir At Thobari; Email: pusatcebu.fkkmk@ugm.ac.id

Study Locations

• Indonesia
  • Jakarta, Indonesia
    • Recruiting
    • Kimia Farma Radio Dalam Clinic and Laboratorium
    • Contact: Research Team
  • Bali
    • Badung, Bali, Indonesia
      • Completed
      • Universitas Udayana Hospital
    • Denpasar, Bali, Indonesia
      • Completed
      • Bali Mandara Hospital
  • Central Java
    • Semarang, Central Java, Indonesia
      • Recruiting
      • Kimia Farma Soetomo Clinic and Laboratorium
      • Contact: Research Team
  • D.I. Yogyakarta
    • Sleman, D.I. Yogyakarta, Indonesia
      • Completed
      • JIH Hospital
    • Yogyakarta, D.I. Yogyakarta, Indonesia
      • Completed
      • Kimia Farma Adisucipto Clinic and Laboratorium
  • West Java
    • Bandung, West Java, Indonesia
      • Recruiting
      • Kimia Farma Diponegoro Clinic and Laboratorium
      • Contact: Research Team

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult males or females aged 18 years and above at the time of consent.
2. Participants who provide a voluntarily consent to participate in the study and sign the consent form.
3. Participants who have previously received homologous 2-dose of SARS-COV-2 Vaccine (either Vero Cell inactivated-Sinopharm SARS-COV-2 Vaccine, CoronaVac SARS-COV-2 Vaccine, or Cominarty/Pfizer mRNA COVID-19 Vaccine) authorized for emergency use, between 6 to 12 months post second prime vaccine dose prior to Day 1.
4. Participants who have negative results for swab SARS-COV-2 rapid antigen test.

Exclusion Criteria:

1. Participants who are unable to follow clinical and follow-up procedures.
2. Participants with acute fever with temperature above 38℃, coughing, breathing difficulty, chills, muscle ache, headache, sore throat, loss of smell, or loss of taste within 72 hours prior to the dosing.
3. Participants with a history of PCR-confirmed SARS-CoV-2 infection in the last 90 days prior to dosing.
4. Female who are pregnant or breastfeeding.
5. Participants with a history of hypersensitivity or allergic reactions including anaphylaxis.
6. Participants with immune dysfunction, including immunodeficiency disorder, or family history of such conditions, except HIV-positive participants in stable/well-controlled condition.
7. Participants who received chronic administration (defined as more than 14 continuous days) of immunosuppressant medication such as immunomodulator, immune-modifying drug, immunoglobulin, immunotherapy, chemotherapy, systemic corticosteroid, etc. except topical steroids or short-term oral steroids (course lasting ≤ 14 days), or blood-derived products in the last 90 days prior to dosing.

8. Participants with a current clinically significant chronic and unstable cardiovascular, endocrine, gastrointestinal, hepatic (including hepatitis B and C), renal, neurological, respiratory, psychiatric or other medical disorders not excluded by other exclusion criteria , that are assessed by the investigator as being clinically unstable within the prior 90 days as evidenced by:

   1. Hospitalization for the condition, including day surgical interventions
   2. New significant organ function deterioration
   3. Needing addition of new treatments or major dose adjustments of current treatments (mild or moderate well-controlled comorbidities are allowed)
9. Participants with hemophilia or people using anticoagulants who are at a risk of serious bleeding from IM injection.
10. Participants with a current dependent on antipsychotic drugs and narcotic analgesics, or suspected of alcohol or drug dependency.
11. Participants who have received or plans to receive other vaccination(s) within 28 days prior to or during study duration (except for influenza vaccine which is not allowed within 14 days before, or 4 weeks after final dose of IP).
12. Participants who have received or have plans to receive other investigational drug(s) while participating in another clinical study or bioequivalence study within 28 days prior to vaccination. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SARS-COV-2 Vaccine (Vero Cell-Sinopharm) Inactivated; One booster dose 0.5 mL IM injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated

Biological: SARS-COV-2 Vaccine (Vero Cell-Sinopharm) Inactivated; SARS-CoV-2 vaccine (Vero cell) inactivated developed by Beijing Bio-Institute Biological Products Co., Ltd, can induce active immunity and prevent diseases caused by the SARS-CoV-2 virus by producing neutralizing antibody. The inactivated SARSCoV-2 Vaccine (Vero cell) is prepared by inoculating Verda Reno cells (Vero cell) with SARS-CoV-2 HB02 strain, culturing, harvesting, inactivating, clarifying, concentrating, purifying and adding aluminum hydroxide adjuvant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The geometric mean titer (GMT) of anti-SARS-CoV-2 neutralizing antibody at 14 and 28 days	To evaluate the immunogenicity at 14 and 28 days after one booster dose of 0.5 mL intramuscular (IM) injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 28 days after one booster dose
The geometric mean fold rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody at 14 and 28 days	To evaluate the immunogenicity at 14 and 28 days after one booster dose of 0.5 mL intramuscular (IM) injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 28 days after one booster dose
The geometric mean titer (GMT) of anti-spike protein receptor binding domain (sRBD) immunoglobulin G (IgG) antibody at 14 and 28 days	To evaluate the immunogenicity at 14 and 28 days after one booster dose of 0.5 mL intramuscular (IM) injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 28 days after one booster dose
The geometric mean fold rise (GMFR) of anti-spike protein receptor binding domain (sRBD) immunoglobulin G (IgG) antibody at 14 and 28 days	To evaluate the immunogenicity at 14 and 28 days after one booster dose of 0.5 mL intramuscular (IM) injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 28 days after one booster dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The geometric mean titer (GMT) of anti-SARS-CoV-2 neutralizing antibody at 90, 180, and 360 days	To evaluate the immunogenicity at 90, 180, and 360 days after one booster dose 0.5 mL IM injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	At 90, 180, and 360 days after one booster
The geometric mean fold rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody at 90, 180, and 360 days	To evaluate the immunogenicity at 90, 180, and 360 days after one booster dose 0.5 mL IM injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	At 90, 180, and 360 days after one booster
The geometric mean titer (GMT) of anti-spike protein receptor binding domain (sRBD) immunoglobulin G (IgG) antibody at 90, 180, and 360 days	To evaluate the immunogenicity at 90, 180, and 360 days after one booster dose 0.5 mL IM injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	At 90, 180, and 360 days after one booster
The geometric mean fold rise (GMFR) of anti-spike protein receptor binding domain (sRBD) immunoglobulin G (IgG) antibody at 90, 180, and 360 days	To evaluate the immunogenicity at 90, 180, and 360 days after one booster dose 0.5 mL IM injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	At 90, 180, and 360 days after one booster
To proportion of solicited adverse events within 7 days after one booster dose	To evaluate the safety profile of one booster dose 0.5 mL IM injection of SARSCOV-2 Vaccine (Vero Cell) Inactivated in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 7 days after one booster
To proportion of unsolicited adverse events within 28 days after one booster dose	To evaluate the safety profile of one booster dose 0.5 mL IM injection of SARSCOV-2 Vaccine (Vero Cell) Inactivated in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 28 days after one booster
To proportion of clinically significant abnormal liver function (AST, ALT, Total Bilirubin) at 14 days and 28 days	To evaluate the safety profile of one booster dose 0.5 mL IM injection of SARSCOV-2 Vaccine (Vero Cell) Inactivated in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 28 days after one booster
To proportion of serious adverse events within 180 days after one booster dose	To evaluate the safety profile of one booster dose 0.5 mL IM injection of SARSCOV-2 Vaccine (Vero Cell) Inactivated in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 180 days after one booster

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To proportion of symptomatic PCR-confirmed SARS-CoV-2 infection within 90 and 180 days after one booster dose	To evaluate proportion of symptomatic PCR-confirmed SARS-CoV-2 infection after one booster dose 0.5 mL IM injection of SARS-COV-2 Vaccine (Vero Cell) Inactivated compared to placebo in participants who had received second dose of SARS-CoV-2 prime vaccine at least 6 months	Within 180 days after one booster

Collaborators and Investigators

• Sponsor: PT. Kimia Farma (Persero) Tbk

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2021
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: December 23, 2021
• First Submitted That Met QC Criteria: December 23, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Actual): September 8, 2022
• Last Update Submitted That Met QC Criteria: September 4, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Safety; Booster; COVID-19; Immunogenicity; Verocell Inactivated Vaccine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: BOOST-VC-0221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No