EEC skin test to diagnose tuberculosis infection in people aged 3 and older

Phase III Clinical Trial to Evaluate the Efficacy and Safety of Recombinant Mycobacterium Tuberculosis Fusion Protein (EEC) for the Diagnosis of Mycobacterium Tuberculosis Infection in People Aged 3 Years and Above

This test checks whether the EEC skin test can accurately detect TB infection in people aged 3 and older, compared with existing skin tests and a blood IGRA.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1784 (estimated)
• Ages: 3 Years and up
• Sex: All
• Sponsor: Chengdu CoenBiotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 8 sites (Beijing, Beijing Municipality and 7 other locations)
• Trial ID: NCT07152639 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, blinded, active-controlled Phase 3 program comparing the investigational EEC skin test to established diagnostics (a recombinant fusion protein EC, tuberculin PPD, and IGRA) across several participant groups. Study 1 compares sensitivity in people with tuberculosis and specificity in healthy volunteers and patients with non-tuberculous lung disease versus the marketed EC reagent using a non-inferiority design. Study 2 enrolls adults who are negative on EEC, TB-PPD, and IGRA, gives BCG vaccination, and compares EEC and TB-PPD responses 12 weeks later to see differences after BCG. Safety and agreement between EEC and the comparator methods are monitored throughout.

Who should consider this trial

Good fit: Ideal participants are people aged 3 years and older, including those with confirmed tuberculosis, healthy community controls, patients with non-tuberculous lung disease, and BCG-vaccinated triple-negative adults for the post-vaccination comparison.

Not a fit: People under 3 years old, those with recent or treated active tuberculosis, or anyone unable to attend follow-up visits or undergo skin testing are unlikely to benefit from participating.

Why it matters

Potential benefit: If successful, EEC could provide a more specific or reliable skin test option for detecting TB infection, including in people who received BCG vaccination.

How similar studies have performed: Recombinant protein skin tests and IGRA blood tests are established TB diagnostics and prior comparative studies have shown variable but useful performance, so this program extends those approaches to a new EEC reagent.

Eligibility criteria

Inclusion Criteria:

* For the general community population

  1. Age 3 years and above at the time of enrollment, regardless of gender;
  2. The individual and/or guardian agree to participate in this trial and sign the informed consent form;
  3. The individual and/or guardian can comply with the requirements of the clinical trial protocol to participate/accompany the participants to participate in follow-up;
  4. No history of tuberculosis (including intrapulmonary and extrapulmonary tuberculosis) after medical history inquiry;
  5. No clinical symptoms of tuberculosis poisoning. Tuberculosis poisoning symptoms refer to obvious systemic symptoms such as fatigue, low fever in the afternoon, loss of appetite, night sweats, etc. in addition to local symptoms such as cough, chest pain, and chest tightness. Women may have endocrine system disorders, such as irregular menstruation, amenorrhea, etc.;
  6. Inclusion criteria for triple-negative population: People with negative results of the first skin test on both arms and IGRA test results (i.e., negative results of EEC, TB-PPD, and IGRA tests).
* For Patients with tuberculosis (including pulmonary tuberculosis)

  1. Age 3 years and above at the time of enrollment, regardless of gender;
  2. Participants aged ≥18 years were diagnosed with tuberculosis/pulmonary tuberculosis according to the diagnostic standard "Standard Tuberculosis Classification of the Health Industry of the People's Republic of China WS196-2017" issued by the health and health authorities of the State Council (recognizing the diagnosis made by comprehensive clinical analysis); participants aged 3-17 years were diagnosed with tuberculosis according to the "Expert Consensus on Diagnosis of Childhood Pulmonary Tuberculosis (2022 Edition)" formulated by the Children's Tuberculosis Professional Committee of the Tuberculosis Branch of the Chinese Medical Association. Including pulmonary tuberculosis and extrapulmonary tuberculosis, of which pulmonary tuberculosis includes bacteria-negative/bacteria-positive pulmonary tuberculosis and primary/relapsed pulmonary tuberculosis; patients with both pulmonary tuberculosis and extrapulmonary tuberculosis can be included and classified as pulmonary tuberculosis;
  3. The individual and/or guardian agree to participate in this trial and sign the informed consent form;
  4. The individual and/or guardian can comply with the requirements of the clinical trial protocol to participate in follow-up.

For Patients with non-tuberculous lung disease

1. Patients with a clear clinical diagnosis of non-tuberculous lung disease, and clinical physicians can exclude pulmonary tuberculosis and extrapulmonary tuberculosis based on the patient's clinical manifestations, imaging and laboratory tests, including pneumonia, lung cancer, bronchitis, bronchiectasis, non-tuberculous mycobacterial disease, chronic obstructive pulmonary disease, etc.;
2. Aged 3 years and above at the time of enrollment, regardless of gender;
3. The individual and/or guardian agree to participate in this trial and sign the informed consent form;
4. The individual or guardian can comply with the requirements of the clinical trial protocol to participate in follow-up.

Exclusion Criteria:

\- For the general community population

1. Those with known or suspected (or high-risk) severe immune diseases, immune function damage or abnormalities (Except for human immunodeficiency virus \[HIV\] infection/HIV infection), including:Those who received immunosuppressants (including chemotherapy) (using medium/high doses of glucocorticoids (≥20mg/d or ≥0.5mg/kg/d prednisone or equivalent other hormones), and the medication time was \>14 days) or immunopotentiators within 3 days before the skin test or during the trial, and those who were evaluated by the researchers to affect the efficacy of the participants; Note: For glucocorticoid drugs: topical inhalation, nasal spray, local injection, application and other external use, as well as long-term physiological replacement therapy for systemic medication such as oral, intramuscular injection, intravenous injection or intravenous drip, there are no restrictions, such as prednisone or other equivalent doses of other drugs with a dose of \<20mg/d (\>5 years old) or \<0.5mg/kg/d (≤5 years old), and the medication time is ≤14 days.
2. Patients with convulsions, epilepsy, history of mental illness and/or family history of mental illness (immediate relatives);
3. Patients with allergic constitution, such as those with a history of allergy to two or more drugs or foods, or those known to be allergic to the components of this drug;
4. Patients with acute infectious diseases (such as measles, whooping cough, influenza, etc.), acute conjunctivitis, acute otitis media, and extensive skin diseases;
5. Patients with acute febrile diseases; or those who have used antipyretic, analgesic and antiallergic drugs within 3 days before the skin test and who have been assessed by the researchers to be likely to affect the study evaluation;
6. Patients with severe skin infections (such as pyoderma, severe eczema, etc.);
7. Those who have used other clinical trial drugs within 3 months before the skin test (except placebo, in vitro diagnostic reagents or non-contact human devices);
8. Those who have received inactivated vaccines within 7 days before the skin test, or attenuated live vaccines within 28 days;
9. Women who are breastfeeding or pregnant, or women of childbearing age who have a positive pregnancy test before enrollment. 10) Those with a history of drug abuse;

11\) Those who the researcher believes have poor compliance, past history, physical examination results that may affect the trial evaluation (such as tattoos, etc.); 12) Exclusion criteria for triple-negative population: Those with contraindications to BCG vaccination, including: ① Those with immunodeficiency or damage (such as AIDS patients); ② Those currently using immunosuppressive drugs or radiotherapy; ③ Those who are allergic to BCG; ④ Those with fever and acute infectious diseases, including active tuberculosis patients; ⑤ Severe chronic diseases (such as heart, brain, vascular diseases, chronic kidney disease).

For Patients with tuberculosis and non-tuberculous lung disease

1. Those with known or suspected (or high-risk) severe immune diseases, immune function damage or abnormalities (Except for human immunodeficiency virus \[HIV\] infection/HIV infection), including: Those who are receiving immunosuppressants (including chemotherapy) (using medium/high doses of glucocorticoids (≥20mg/d or ≥0.5mg/kg/d), medication time\>14 days) or immunoenhancers within 3 days before the skin test or during the trial, and those who are assessed by the researchers to affect the efficacy of the participants; Note: For glucocorticoid drugs: topical inhalation, nasal spray, local injection, application and other external use, as well as long-term physiological replacement therapy for systemic medication such as oral, intramuscular injection, intravenous injection or intravenous drip, there are no restrictions, such as prednisone or other equivalent doses of other drugs at a dose of \<20mg/d (\>5 years old) or \<0.5mg/kg/d (≤5 years old), medication time ≤14 days.
2. Patients with convulsions, epilepsy, history of mental illness and/or family history of mental illness (immediate relatives);
3. Patients with allergic constitution, such as those with a history of allergy to two or more drugs or foods, or those known to be allergic to the components of this drug;
4. Patients with acute infectious diseases (such as measles, whooping cough, influenza, etc.), acute conjunctivitis, acute otitis media, and extensive skin diseases;
5. Patients with severe skin infections (such as pyoderma, severe eczema, etc.);
6. Patients who have used other clinical trial drugs within 3 months before the skin test (except placebo, in vitro diagnostic reagents or non-human contact devices);
7. Patients who have received inactivated vaccines within 7 days before the skin test, or attenuated live vaccines within 28 days;
8. Women who are breastfeeding or pregnant, or women of childbearing age who have a positive pregnancy test before enrollment.
9. Patients with a history of drug abuse;
10. Any situation that the researcher believes has poor compliance, past history, and physical examination results may affect the trial evaluation (such as tattoos, etc.).

Where this trial is running

Beijing, Beijing Municipality and 7 other locations

• Beijing Chest Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Changsha Center Hospital — Hunan, Changsha, China (Recruiting)
• LiuZhou People's Hospital — Liuzhou, Guangxi, China (Recruiting)
• The First Affiliated Hospital of Xinxiang Medical College — Xinxiang, Henan, China (Not_yet_recruiting)
• Wuhan Pulmonary Hospital — Wuhan, Hubei, China (Recruiting)
• Wuhan Central Hospital — Wuhan, Hubei, China (Recruiting)
• Yichang Central People's Hospital — Yichang, Hubei, China (Recruiting)
• Public health clinical center of chengdu — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Study coordinator: Naihui Chu，PhD

Conditions Tuberculosis