Clinical trial NCT06305104: Clinical Trial to Explore the Skin Test Dosage of EEC in People Aged 18 to 65 Years Old and the Safety and Preliminary Efficacy in People Aged 3 to 75 Years Old.
Official title: Phase 2 Clinical Trial of Randomized, Blinded, Positive-controlled to Explore the Skin Test Dosage of EEC in People Aged 18 to 65 Years Old and the Safety and Preliminary Efficacy in People Aged 3 to 75 Years Old.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Tuberculosis
Lead sponsor: Chengdu CoenBiotech Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Beijing Chest Hospital, Capital Medical University
name: Wuhan Institute for Tuberculosis Control
name: The Public Health Clinical Center of Chengdu
name: Xuzhou Infectious Disease Hospital
name: Jiangsu Province Centers for Disease Control and Prevention
name: Changde First People's Hospital
First posted: 2024-03-12
Enrollment: 420
Sex: ALL
Minimum age (years): 3
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This is a randomized, blind, positive-controlled study to explore the skin test dosage of recombinant mycobacterium tuberculosis fusion protein ( EEC) in the population aged 18 to 65 years old , and to further evaluate the safety and preliminary efficacy of EEC in the population aged 3 to 75 years old.

In the first stage,180 healthy subjects, 140 tuberculosis（TB）subjects and 40 non-TB subjects with lung diseases aged 18 to 65 years old are divided into different groups through a randomized, blind methods. Every group carry out a low-dose (2.5μg/ml) or high-dose (5μg/ml) study, with 180 subjects in each dose group .Every subject injects intradermally EEC and EC randomly in both arms of the same person. Evaluate the consistency of assay results of EEC, EC and Interferon-Gamma Release Assay（IGRA）.Evaluate the sensitivity, specificity and consistency of assay results of EEC, EC and IGRA in healthy people, TB patients and non-TB patients with lung diseases, and determine the optimal dose of EEC for clinical auxiliary diagnosis of tuberculosis.

In the second stage, 60 healthy subjects and TB subjects aged 3-17 years and 66-75 years old are divided into different groups through a randomized, open, single-arm method with the target dose. Evaluate the safety, tolerance and preliminary efficacy of target dose of EEC in healthy people and TB patients aged 3 to 17 years old and 66 to 75 years old.

Detailed description: In the first stage,180 healthy subjects, 140 TB subjects and 40 non-TB subjects with lung diseases which meet the standard respectively are divided into different groups through a randomized blind methods.Every group carry out a low-dose (2.5μg/ml) or high-dose (5μg/ml) study, with 180 subjects in each dose group.

Each subject's left and right arms will be randomly assigned to receive an intradermal injection of the experimental drug EEC and the control drug inoculated in both arms of the same person. A drug(EEC or EC) is injected in left arm first, observe 30 min and if no obvious adverse reaction ,then another drug (EEC or EC) will be injected in right arm. Observe and record the vital signs (breathing, heart rate, blood pressure ,temperature),the skin specific reaction (diameters of flush and induration of injection site) at 24h, 48h, 72h, 96h, and 7 days after skin test;local reactions (redness, pain, swelling, rash,itching) and a variety of adverse events. Evaluate the sensitivity , specificity and consistency rate of assay results of EEC, EC and IGRA in healthy subjects, TB patients and non-TB patients with lung diseases,determine the optimal dose of EEC for clinical auxiliary diagnosis of tuberculosis,and further evaluate the safety of EEC in healthy subjects, TB patients and non-TB patients with lung diseases.

In the second stage, 60 subjects aged 3-17 years old (30 cases) and 66-75 years old (30 cases) are enrolled, including 30 healthy subjects and 30 TB patients. Every subject is divided into different groups through a randomized, open label method, and receive a single intradermal injection of experimental drug (EEC) in one arm. Observe and record the vital signs (breathing, heart rate and temperature); laboratory examination and electrocardiogram (ECG) ;the skin specific reactions of injection site at 4h,8h,24h, 48h, 72h, 96h, and 7 days after skin test ; local reactions and a variety of adverse events，to further evaluate the safety and preliminary efficacy of EEC in people aged 3 to 75 years old.

Eligibility criteria: Inclusion Criteria:

* For healthy subjects:

  1. At the time of enrollment - For healthy subjects:enrollment is 3 \~ 75 years old (including 3 years old and 75 years old), regardless of gender ;
  2. Guardians of persons aged 3-7 years , persons aged 8-17 years old and their guardians, persons aged 18-75 years old themselves and/or their guardians (spouse or children) agree to participate in this trial and sign an informed consent form;
  3. The person and/or guardian can comply with the requirements of the clinical trial protocol to participate in /accompany the subject to follow- up visits;
  4. After medical history inquiry, there is no history of tuberculosis (including intrapulmonary and external tuberculosis ) and close contact history with tuberculosis patients (referring to direct contact with registered tuberculosis patients from 3 months before diagnosis to 14 days after starting anti-tuberculosis treatment);
  5. Those who have no clinical symptoms of tuberculosis poisoning and whose chest imaging examination (for subjects aged 15 to 75 years old) is normal or abnormal without clinical significance;
  6. Normal or abnormal measurements of vital signs ( axillary temperature, pulse , respiration , blood pressure ) and electrocardiogram have no clinical significance; \[ The axillary temperature of all subjects was measured \< 37.3°C ; blood pressure was measured in subjects aged 18-75 years (systolic blood pressure \<160 millimetres of mercury（mmHg） and diastolic blood pressure \<100mmHg) ; pulse and respiration were determined by the researcher based on the subject's age\]
  7. Physical examinations are normal or abnormal with no clinical significance;
  8. Laboratory tests including blood routine, urine routine, and blood biochemistry tests were all normal or abnormal with no clinical significance.
* For patients with tuberculosis (including pulmonary tuberculosis):

  1. Those who was diagnosed with tuberculosis/ pulmonary tuberculosis according to the "People's Republic of China Health Industry Standard Pulmonary Tuberculosis Diagnostic Criteria " combined with the "Technical Guidelines for Tuberculosis Prevention and Control in China ( 2021 Edition )" (accepted clinical comprehensive analysis diagnosis);
  2. The age at the time of enrollment is 3 to 75 years old (including 3 years old and 75 years old), regardless of gender ;
  3. Guardians of persons aged 3-7 years old, persons aged 8-17 years old and their guardians, persons aged 18-75 years old themselves and/ or their guardians (spouse or children) agree to participate in this trial and sign an informed consent form;
  4. The person and /or guardian may comply with the requirements of the clinical trial protocol and participate in follow-up visits.
* For patients with non-tuberculous lung disease

  1. Patients with clear clinical diagnosis of pulmonary disease, and the clinician can rule out pulmonary tuberculosis and extrapulmonary tuberculosis based on the patient's clinical manifestations, imaging and laboratory tests (including IGRA );
  2. Age at the time of enrollment is 18 to 65 years old (including 18 years old and 65 years old), regardless of gender;
  3. Those who agree to participate in this trial and sign the informed consent form;
  4. Those who may comply with the requirements of the clinical trial protocol and participate in follow-up visits

Exclusion Criteria:

* Those with known or suspected (or high-risk) severe immune diseases, immune function impairment or abnormalities ( except HIV infection /AIDS ), including:
* who have convulsions, epilepsy, a history of mental illness and / or a family history of mental illness (immediate relatives);
* People with allergies, such as those who have a history of allergies to two or more drugs or foods, or those who are known to be allergic to the components of this medicine;
* Those currently suffering from acute infectious diseases (such as measles, whooping cough, influenza, etc.), acute conjunctivitis, acute otitis media, and generalized skin diseases;
* After consultation, have a history of past or current serious heart, liver, kidney, digestive system, respiratory system, nervous system, mental disorder and metabolic disorders;
* Those who are currently suffering from acute febrile illness; or those who have used antipyretic, analgesic and anti-allergic drugs within 3 days before the skin test and which may affect the research evaluation as assessed by the researcher ;
* People with serious infections (such as pyoderma, severe eczema, etc.);
* who are participating in or participating in any other new drug clinical trials within 3 months;
* Have received non-live vaccines within 7 days before the skin test , or have received live attenuated vaccines within 28 days ;
* Lactating or pregnant women, or female subjects of childbearing age who have a positive pregnancy test before enrollment and who have not taken effective contraceptive measures 2 weeks before enrollment.
* Those with a history of drug abuse;
* Any other circumstances that the investigator believes may affect the evaluation of the study.

Primary outcomes:
measure: Sensitivity of different doses of EEC and control EC in pulmonary tuberculosis patients aged 18 to 65 years ;
timeFrame: 7days after injection
measure: specificity of different doses of EEC and control EC in healthy subjects aged 18 to 65 years and patients with non-tuberculous lung disease ;
timeFrame: 7days after injection
measure: The skin test site specific reaction at 4h,8h (only for stage 2);24h, 48h, 72h, 96h, and 7 days after skin test. Those with average diameter of induration/redness is ≥5 mm will be considered to positive.
timeFrame: 7days after injection
Secondary outcomes:
measure: Receiver operator characteristic curve(ROC) of different doses of EEC to evaluate the optimal diagnostic test cut-off value of the test drug.
timeFrame: 7days after injection
measure: Area under the curve(AUC) of different doses of EEC to evaluate the optimal diagnostic test cut-off value of the test drug.
timeFrame: 7days after injection
measure: In healthy people, patients with tuberculosis and patients with non-tuberculous lung diseases, the consistency rates of the three detection reagents EEC , EC and IGRA were evaluated respectively.
timeFrame: 7days after injection
measure: Incidence of adverse events and serious adverse events at injection and non-injection sites，abnormal incidence of laboratory indicators and vital signs during the study period.
timeFrame: 7days after injection
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chest Hospital
state: Beijing
city: Wuhan
country: China
facility: Wuhan Institute for Tuberculosis Control
state: Hubei
city: Changde
country: China
facility: Changde First People's Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Centers for Disease Control and Prevention
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Infectious Disease Hospital
state: Jiangsu
city: Chengdu
country: China
facility: Public health clinical center of chengdu
state: Sichuan
Study officials:
References: