Clinical trial NCT05899179: Clinical Study of Recombinant Mycobacterium Tuberculosis Fusion Protein for 65-year-olds and Above
Official title: A Multicenter, Randomized, Double-blind, Controlled Phase Ⅲ Trial of Recombinant Mycobacterium Tuberculosis Fusion Protein (EC) for the Diagnosis of Mycobacterium Tuberculosis Infection in 65-year-olds and Above
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Latent Tuberculosis Infection
Lead sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-06-12
Enrollment: 780
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: A multicenter, randomized, blind, controlled trial design was used to select 240 tuberculosis (TB) patients, 120 non-tuberculous community population with other lung diseases, and 420 healthy community population without other lung diseases who met the inclusion criteria of this study. Blood supply specific gamma-interferon (T-SPOT) detection was performed first. Then, EC and Purified Protein derivation of tuberculin (TB-PPD) skin tests were performed on both arms, and the recorded results were observed. The first 24 cases of TB patients, the first 12 cases of non-tuberculous community population with other lung diseases, and the first 42 cases of healthy community population without other lung diseases were included in the trial subgroup. Physical examination, blood routine, urine routine, liver and kidney function, and electrocardiogram tests were required before and 7 days after skin test after study number assignment.

Detailed description: A multicenter, randomized, blind, controlled trial design was adopted in this study. Subjects were enrolled in this clinical study after being qualified by physical examination, vital signs detection (body temperature, blood pressure, pulse and respiration), chest imaging (DR/CT) examination, mycobacterium tuberculosis etiology examination, HIV antibody detection, fasting blood glucose detection, etc.

A total of 240 TB patients, 120 non-tuberculous community people with other lung diseases, and 420 healthy community people without other lung diseases were selected for inclusion in this study. Blood samples were collected for specific gamma-interferon (T-SPOT) detection, and then EC and TB-PPD in the same double arm skin test were used to observe and record the results.

The first 24 cases of TB patients, the first 12 cases of non-tuberculous community population with other lung diseases, and the first 42 cases of healthy community population without other lung diseases were included in the trial subgroup. Physical examination, blood routine, urine routine, liver and kidney function, and electrocardiogram tests were required before and 7 days after skin test after study number assignment.

Vital signs (body temperature, blood pressure, pulse and respiration) were measured 30min and 24h after skin test, and body temperature was measured 48h and 72h after skin test. The skin reaction at the injection site was observed at 0min, 24h, 48h and 72h after skin test.

Eligibility criteria: Inclusion Criteria:

* 65 years old and above (≥ 65 years old), male or female, the subjects themselves voluntarily participate in this study, sign the informed consent form, and can understand and comply with the requirements of the trial protocol to participate in follow-up.
* Normal underarm body temperature (\< 37.3 °C);
* Tuberculosis patients: pulmonary tuberculosis patients and extrapulmonary tuberculosis patients diagnosed by researchers as confirmed cases of tuberculosis and clinically diagnosed cases. Refer to the "WS288-2017 Tuberculosis Diagnostic Criteria" to formulate the diagnostic criteria for pulmonary tuberculosis in this protocol, see Annex 1 for details; The diagnostic criteria for extrapulmonary tuberculosis were formulated with reference to the Technical Guidelines for Tuberculosis Prevention and Control in China (2021 edition of the Chinese Center for Disease Control and Prevention), as detailed in Annex 2.
* Non-tuberculous community population with other lung diseases: there is a clear lung disease, but the study physician can exclude pulmonary tuberculosis based on the patient's clinical manifestations, chest imaging and laboratory tests. Diagnostic criteria for their main types of nontuberculous other lung diseases can be found in Annex 3;
* Community healthy people without other lung diseases: those who have no history of tuberculosis, no suspicious symptoms of tuberculosis, no history of respiratory tract and recent respiratory symptoms, and no obvious abnormalities in both lungs on chest imaging (DR) examination; After consultation, there is no history of heart, liver, kidney, digestive tract, nervous system, or psychiatric abnormalities.

Exclusion Criteria:

* Combined with the following serious diseases, such as advanced tumors, acute exacerbation of chronic obstructive pulmonary disease, acute or progressive liver disease or kidney disease, decompensated stage of congestive heart failure, autoimmune diseases (except those who do not need to use immune agents in the stable period), primary immunodeficiency diseases, etc.;
* Those suffering from acute infectious diseases (such as measles, pertussis, influenza, pneumonia, etc.), acute conjunctivitis, acute otitis media, extensive skin diseases and allergies;
* Those with known or suspected (or high-risk occurrence possibility) immune impairment or abnormalities, such as those receiving immunosuppressants or immune booster therapy, receiving glucocorticoids, immunoglobulin preparations other than the gastrointestinal tract or blood products or plasma extracts within 1 month;
* Those who have positive human immunodeficiency virus (HIV) antibody test results;
* Those who are participating in other new drug clinical trials or have participated in any other new drug clinical trials within 3 months before this clinical trial;
* Fasting blood glucose ≥ 10mmol/L after drug control;
* Blood pressure range: systolic blood pressure ≥ 180 mmHg and (or) diastolic blood pressure ≥ 110 mmHg (those who take drugs are uncontrollable);
* Any situation that the investigator believes is poor adherence or may affect the evaluation of the trial.

Primary outcomes:
measure: Measure the diameter of redness or induration at the reaction site
timeFrame: The skin test was performed at 0 minute after injection.
measure: Measure the diameter of redness or induration at the reaction site
timeFrame: The skin test was performed at 24 hours after injection.
measure: Measure the diameter of redness or induration at the reaction site
timeFrame: The skin test was performed at 48 hours after injection.
measure: Measure the diameter of redness or induration at the reaction site
timeFrame: The skin test was performed at 72 hours after injection.
measure: Evaluate the incidence of all adverse events
timeFrame: Incidence of all adverse events within 7 days after injection.
measure: Evaluate the incidence of serious adverse event (SAE)
timeFrame: Incidence of SAE within 28 days after full vaccination
measure: In subgroup, count the number of patients with changes in clinical significance of blood routine test before skin test compared with that 7 days after skin test
timeFrame: before injection
measure: In subgroup, count the number of patients with changes in clinical significance of urine routine test before skin test compared with that 7 days after skin test
timeFrame: before injection
measure: In subgroup, count the number of patients with changes in clinical significance of liver and kidney function test before skin test compared with that 7 days after skin test
timeFrame: before injection
measure: In subgroup, count the number of patients with changes in clinical significance of electrocardiogram test before skin test compared with that 7 days after skin test
timeFrame: before injection
measure: In subgroup, count the number of patients with changes in clinical significance of blood routine test 7 days after skin test compared with that before skin test
timeFrame: 7days after injection
measure: In subgroup, count the number of patients with changes in clinical significance of urine routine test 7 days after skin test compared with that before skin test
timeFrame: 7days after injection
measure: In subgroup, count the number of patients with changes in clinical significance of liver and kidney function test 7 days after skin test compared with that before skin test
timeFrame: 7days after injection
measure: In subgroup, count the number of patients with changes in clinical significance of electrocardiogram test 7 days after skin test compared with that before skin test
timeFrame: 7days after injection
Secondary outcomes:
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical University
state: Anhui
city: Hefei
country: China
facility: Anhui Chest Hospital
state: Anhui
city: Guangzhou
country: China
facility: Guangzhou Municipal Hospital of Chest Medicine
state: Guangdong
city: Shenzhen
country: China
facility: The Third People's Hospital Of Shenzhen
state: Guangdong
city: Liuzhou
country: China
facility: LiuZhou People's Hospital
state: Guangxi
city: Changsha
country: China
facility: Changsha Central Hospital
state: Hu Nan
city: Wuxi
country: China
facility: Wuxi NO.5 People's Hospital
state: Jiangsu
city: Wuhan
country: China
facility: Wuhan Institute for Tuberculosis Control
Study officials:
affiliation: Shenzhen Third People's Hospital
name: Shuihua Lu, bachelor
role: PRINCIPAL_INVESTIGATOR
References: