Study on Three Doses of an Inactivated COVID-19 Vaccine in Chinese Pulmonary Tuberculosis Patients

Safety and Immunogenicity of Three Doses of an Inactivated SARS-CoV-2 Vaccine in Chinese Pulmonary Tuberculosis Patients Aged 18-75 Years: a Randomized, Double-blind, Parallel-controlled Clinical Trial

This is a randomized, double-blind, parallel-controlled study, for evaluation of safety and immunogenicity of three doses of an inactivated COVID-19 vaccine (CoronaVac) in pulmonary tuberculosis patients aged 18-75 years. 200 tuberculosis patients and 40 healthy adults aged 18-75 years will be recruited in this study. Of them, 200 pulmonary tuberculosis patients will be randomized at a 1:1 ratio to receive two doses of standard dosage CoronaVac plus one dose of double dosage CoronaVac or two doses of standard dosage CoronaVac plus one dose of standard dosage CoronaVac at a schedule of 0, 28, 56 days, respectively. Other 40 healthy subjects served as an external control group will be vaccinated with two doses of standard dosage CoronaVac at a schedule of 0, 28 days. The occurrence of adverse events within 28 days after each dose vaccination and serious adverse events within 3 months after full vaccination will be observed. In addition, blood samples will be collected on day 0 before the first dose and 28 days and 3 months after the last dose vaccination in all participants and 28 days after second dose in pulmonary tuberculosis patients. Each subject will remain in this study for 5 months (healthy group) or 6 months (tuberculosis group).

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Pulmonary Tuberculosis
• Intervention / Treatment: Biological: Standard dosage inactivated vaccine; Biological: Double dosage inactivated vaccine

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jing-Xin Li, PhD; Phone Number: #86-25-83759913; Email: jingxin42102209@126.com

Study Locations

• China
  • Jiangsu
    • Huai'an, Jiangsu, China, 223001
      • Recruiting
      • Huai'an No.4 People's Hospital
      • Contact: Jing-Xin Li, Ph.D; Phone Number: #86-25-83759913; Email: jingxin42102209@126.com
    • Taizhou, Jiangsu, China, 225300
      • Recruiting
      • Taizhou People's Hospital
      • Contact: Jing-Xin Li, Ph.D; Phone Number: #86-25-83759913; Email: jingxin42102209@126.com
    • Wuxi, Jiangsu, China, 214000
      • Recruiting
      • Wuxi No.5 People's Hospital
      • Contact: Jing-Xin Li, Ph.D; Phone Number: #86-25-83759913; Email: jingxin42102209@126.com
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • Xuzhou Infectious Disease Hospital
      • Contact: Jing-Xin Li, PhD; Phone Number: #86-25-83759913; Email: jingxin42102209@126.com
      • Principal Investigator: Jing-Xin Li, PhD
    • Yancheng, Jiangsu, China, 224000
      • Recruiting
      • Binhai County Hospital of Chinese medicine
      • Contact: Jing-Xin Li, Ph.D; Phone Number: #86-25-83759913; Email: jingxin42102209@126.com
    • Zhenjiang, Jiangsu, China, 212300
      • Recruiting
      • Danyang Center for Disease Control and Prevention
      • Contact: Jing-Xin Li, Ph.D; Phone Number: #86-25-83759913; Email: jingxin42102209@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for pulmonary tuberculosis patients:

1. Pulmonary tuberculosis patients aged 18-75 years who have not received COVID-19 vaccine.
2. The condition is determined to be stable by the clinician.
3. The subjects can provide with informed consent and sign informed consent form (ICF).
4. The subjects are able to and willing to comply with the requirements of the clinical trial program and could complete the follow-up of the study.
5. Axillary temperature ≤ 37.0℃.

Inclusion criteria for healthy participants:

1.Healthy subjects aged 18-75 years who have not received COVID-19 vaccine. 2.The subjects can provide with informed consent and sign informed consent form (ICF).

3.The subjects are able to and willing to comply with the requirements of the clinical trial program and could complete the follow-up of the study.

4.Axillary temperature ≤ 37.0℃. Exclusion criteria for the first vaccination

1. Medical history or family history of convulsion, epilepsy, encephalopathy and psychosis.
2. HIV positive.
3. Cancer patients under treatment.
4. Allergic to any component of the research vaccines, or a history of hypersensitivity or serious reactions to vaccination.
5. Women with positive urine pregnancy test, pregnant or breast-feeding, or have a pregnancy plan in this study.
6. Severe chronic diseases or condition in progress cannot be controlled.( Grade 3 or higher as defined in the guidelines for the classification of adverse events in clinical trials for prophylactic vaccines).
7. Transaminase ≥ 3 times ULN or total bilirubin ≥2 times ULN, or other serious adverse reactions as determined by the clinician for antituberculosis treatment.
8. Congenital or acquired angioedema / neuroedema.
9. Asplenia or functional asplenia.
10. Thrombocytopenia or other clotting disorder (this may contraindicate intramuscular injection).
11. Immunosuppressant therapy, antiallergic therapy, cytotoxic therapy, high dose inhaled corticosteroid over the past 6 months (excluding corticosteroid spray for allergic rhinitis, surface corticosteroid for acute non-complicated dermatitis, and corticosteroid with dose less than 20mg/ day)
12. Received blood products within 4 months before vaccination.
13. Received other investigational drugs within 1 month prior to receiving the investigational vaccines.
14. Received other live attenuated vaccines within 1 month prior to receiving the investigational vaccines.
15. Received subunit or inactivated vaccine within 14 days prior to receiving investigational vaccine.
16. Any medical, psychological, social or other conditions that, in the investigator's judgment, are inconsistent with the study protocol or affect the subjects' informed consent Exclusion criteria for subsequent vaccination

1.Those who have had a severe allergic reaction after a previous dose of vaccine.

2.Serious adverse events causally related to the previous vaccination. 3.The newly discovered or newly emerging cases who don't meet the inclusion criteria or meet the exclusion criteria for the first dose, the investigator will decide whether they will continue to participate in the study.

4.Other reasons the investigator consider for exclusion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational vaccine group 1; 100 tuberculosis patients will receive two doses of standard dosage CoronaVac plus one dose of double dosage CoronaVac at a schedule of 0, 28, 56 days.	Biological: Standard dosage inactivated vaccine; This vaccine contains 600 SU of SARS-CoV-2 antigen, which is produced by Sinovac Research & Development Co., Ltd. 0.5 ml / bottle.; Other Names: Standard dosage CoronaVac; Biological: Double dosage inactivated vaccine; This vaccine contains 1200 SU of SARS-CoV-2 antigen, which is produced by Sinovac Research & Development Co., Ltd. 0.5 ml / bottle.; Other Names: Double dosage CoronaVac
Experimental: Investigational vaccine group 2; 100 tuberculosis patients will receive two doses of standard dosage CoronaVac plus one dose of standard dosage CoronaVac at a schedule of 0, 28, 56 days.	Biological: Standard dosage inactivated vaccine; This vaccine contains 600 SU of SARS-CoV-2 antigen, which is produced by Sinovac Research & Development Co., Ltd. 0.5 ml / bottle.; Other Names: Standard dosage CoronaVac; Biological: Double dosage inactivated vaccine; This vaccine contains 1200 SU of SARS-CoV-2 antigen, which is produced by Sinovac Research & Development Co., Ltd. 0.5 ml / bottle.; Other Names: Double dosage CoronaVac
Active Comparator: Standard regimen group; 40 healthy subjects will receive two doses of standard dosage CoronaVac at a schedule of 0, 28 days.	Biological: Standard dosage inactivated vaccine; This vaccine contains 600 SU of SARS-CoV-2 antigen, which is produced by Sinovac Research & Development Co., Ltd. 0.5 ml / bottle.; Other Names: Standard dosage CoronaVac

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse reaction within 28 days after each dose	Incidence of adverse reaction within 28 days after each dose.	within 28 days after each dose
GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the second dose.	GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the second dose.	On day 28 after the second dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of solicited adverse events within 7 days after each dose.	Incidence of solicited adverse events within 7 days after each dose.	within 7 days after each dose
Incidence of adverse events within 28 days after each dose.	Incidence of adverse events within 28 days after each dose.	within 28 days after each dose
Incidence of unsolicited adverse events within 28 days after each dose.	Incidence of unsolicited adverse events within 28 days after each dose.	within 28 days after each dose
Incidence of serious adverse events (SAE) till the 3 months after the last vaccination.	Incidence of serious adverse events (SAE) till the 3 months after the last vaccination.	within 3 months after the last vaccination
GMT of anti-S protein of SARS-CoV-2 binding antibodies on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients.	GMT of anti-S protein of SARS-CoV-2 binding antibodies measured by ELISA on day 28 and month 3 after the last dose in all groups and day 28 after second dose in tuberculosis patients.	on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients
Fold increase of anti-S protein of SARS-CoV-2 binding antibodies on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients.	Fold increase of anti-S protein of SARS-CoV-2 binding antibodies on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients.	on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients
GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 and month 3 after the last dose in pulmonary tuberculosis patients.	GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 and month 3 after the last dose in pulmonary tuberculosis patients.	on day 28 and month 3 after the last dose in pulmonary tuberculosis patients
8. Fold increase of neutralizing antibodies against live SARS-CoV-2 virus on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients.	Fold increase of neutralizing antibodies against live SARS-CoV-2 virus on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients.	on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMT of neutralizing antibodies against SARS-CoV-2 variants on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients.	GMT of neutralizing antibodies against SARS-CoV-2 variants on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients.	on day 28 and month 3 after the last dose in all groups and day 28 after second dose in pulmonary tuberculosis patients

Collaborators and Investigators

• Sponsor: Jiangsu Province Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Li-mei Zhu, Jiangsu Provincial Center for Diseases Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2021
• Primary Completion (Anticipated): December 10, 2022
• Study Completion (Anticipated): March 10, 2023

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: December 3, 2021
• First Posted (Actual): December 8, 2021

Study Record Updates

• Last Update Posted (Actual): August 16, 2022
• Last Update Submitted That Met QC Criteria: August 12, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• 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; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; COVID-19; Tuberculosis; Tuberculosis, Pulmonary; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: JSVCT134

Drug and device information, study documents

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