Tuberculosis Clinical Trial
Official title:
Phase IIa Clinical Study of Recombinant Mycobacterium Tuberculosis Antigen ESAT6-CFP10
Choose healthy subjects and patients with TB, distribute them into different dose groups according to the recombinant EC allergen dose from low to high average. Conducting clinical trials of TB-PPD or placebo as controlled arms intradermal injection. Do specific interferon gamma detection before the skin test,after the test 72h±2h and 144h±2h. Evaluate the safety of the recombinant EC allergy , and provide the appropriate dose range for phase IIb clinical trials.
Status | Completed |
Enrollment | 144 |
Est. completion date | August 2014 |
Est. primary completion date | June 2014 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria of healthy subjects: 1. 18 to 65 years old 2. Consent and signed ICF(informed consent forms) 3. Comply with follow-up 4. No history or family history of TB(tuberculosis) 5. Without the internal and external of pulmonary tuberculosis ; no symptoms of respiratory tract and other body parts for TB 6. The examination such as X-ray chest radiograph, sputum bacteria confirmed non-tuberculosis (TB) 7. No uncontrolled kinds of acute or chronic disease or acute infectious diseases or skin disease or skin allergies due to a variety of causes 8. Physical condition : No obvious heart, liver, kidney, gastrointestinal tract, nervous system, mental disorder and metabolic abnormalities and other medical history from signed informed consent to the injection within four weeks prior to delivery ;by the comprehensive physical examination showed electrocardiogram, blood pressure, heart rate, breathing and laboratory tests, including blood, urine routine, liver, kidney and other various biochemical test all without exception or slightly unusual but does not affect our research 9. Did not attend any other new drug clinical trials and not vaccinate prevention products and immunoglobulin for nearly 3 months 10. Normal axillary temperature(quiet condition =37.0 ?) 11. No smoking, no alcohol and drinking caffeinated beverages during the study Exclusion Criteria of Healthy volunteers: 1. Has the following serious disease, such as advanced cancer, diabetes, chronic obstructive pulmonary disease (copd) in acute episodes, acute/ progressive liver disease or kidney disease, congestive heart failure, etc 2. Have seizures, epilepsy, brain and nervous system symptoms or signs of history 3. Has known or suspected (or risk possible) immune damaged or abnormal functional , accept glucocorticoid and immunosuppressants or immunopotentiator treatment, outside the gastrointestinal tract protein or blood products or plasma extraction in 3 months, immunodeficiency virus infection or related diseases 4. Has acute febrile diseases and infectious diseases 5. Participate in other new drug clinical trials 6. Participated in any other new drug clinical trials in 3 months 7. Allergic people who have histories of allergy to two or more drugs/food allergy and physical scars, are allergic to alcohol or drugs known to the group of points 8. Women who are in pregnancy or lactation 9. People with mental or physical disabilities 10. Researchers consider that any conditions may affect the trial evaluation Inclusion Criteria of TB (tuberculosis)subjects: 1. Diagnosis TB according to the health of the People's Republic of China industry standard WS 288-2008 tuberculosis diagnostic criteria 2. Aged 18 to 65 years old 3. Consent and signed ICF to participate in this study 4. Comply with the requirements of the clinical research plan for follow-up Exclusion Criteria of TB volunteers: 1. Have the following serious disease, such as advanced cancer, diabetes, chronic obstructive pulmonary disease (copd) in acute episodes, acute/ progressive liver disease or kidney disease, congestive heart failure, etc 2. Have seizures, epilepsy, brain and nervous system symptoms or signs of history; 3. Have known or suspected (or risk possible) immune damaged or abnormal functional , accept glucocorticoid and immunosuppressants or immunopotentiator treatment, outside the gastrointestinal tract protein or blood products or plasma extraction in 3 months, immunodeficiency virus infection or related diseases 4. People in the pyrogenic stage with febrile diseases or infectious diseases (non tuberculosis) 5. Participate in other new drug clinical trials 6. Participated in any other new drug clinical trials in 3 months; 7. Allergic people who have histories of allergy to two or more drugs/food allergy and physical scars, are allergic to alcohol or drugs known to the group of points; 8. Women who are in pregnancy or lactation; 9. People with mental or physical disabilities; 10. Researchers consider that any conditions may affect the trial evaluation. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. | Fourth Military Medical University, Proswell Medical Corporation, Shanghai Public Health Clinical Center, Tianjin Haihe Hospital |
Aagaard C, Govaerts M, Meikle V, Vallecillo AJ, Gutierrez-Pabello JA, Suarez-Güemes F, McNair J, Cataldi A, Espitia C, Andersen P, Pollock JM. Optimizing antigen cocktails for detection of Mycobacterium bovis in herds with different prevalences of bovine tuberculosis: ESAT6-CFP10 mixture shows optimal sensitivity and specificity. J Clin Microbiol. 2006 Dec;44(12):4326-35. Epub 2006 Sep 27. — View Citation
Brusasca PN, Colangeli R, Lyashchenko KP, Zhao X, Vogelstein M, Spencer JS, McMurray DN, Gennaro ML. Immunological characterization of antigens encoded by the RD1 region of the Mycobacterium tuberculosis genome. Scand J Immunol. 2001 Nov;54(5):448-52. — View Citation
Ravn P, Munk ME, Andersen AB, Lundgren B, Lundgren JD, Nielsen LN, Kok-Jensen A, Andersen P, Weldingh K. Prospective evaluation of a whole-blood test using Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP-10 for diagnosis of active tuberculosis. Clin Diagn Lab Immunol. 2005 Apr;12(4):491-6. — View Citation
van Pinxteren LA, Ravn P, Agger EM, Pollock J, Andersen P. Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clin Diagn Lab Immunol. 2000 Mar;7(2):155-60. — View Citation
Weldingh K, Andersen P. ESAT-6/CFP10 skin test predicts disease in M. tuberculosis-infected guinea pigs. PLoS One. 2008 Apr 23;3(4):e1978. doi: 10.1371/journal.pone.0001978. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in healthy participants at 24 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the healthy participants' arm are positive reaction. The percentage of negative(negative number/total number*100%) is the specificity of ESAT6-CFP10 . |
24 hours after intradermal injection | No |
Primary | Number of Tuberculosis (TB) Participants Positive for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 | The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in TB participants at 24 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the participants' arm are positive reaction. | 24 hours after intradermal injection | Yes |
Primary | Number of Healthy Participants Negative for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in healthy participants at 48 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the healthy participants' arm are positive reaction. | 48 hours after intradermal injection | Yes |
Primary | Number of Tuberculosis (TB) Participants Positive for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10 | The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in TB participants at 48 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the participants' arm are positive reaction. | 48 hours after intradermal injection | Yes |
Primary | Number of Healthy Participants Negative for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in healthy participants at 72 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the healthy participants' arm are positive reaction. The percentage of negative(negative number/total number*100%) is the specificity of ESAT6-CFP10 |
72 hours after intradermal injection | Yes |
Primary | Number of Tuberculosis (TB) Participants Positive for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10 | The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in TB participants at 72 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the participants' arm are positive reaction. | 72 hours after intradermal injection | Yes |
Primary | Number of Healthy Participants Negative for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in healthy participants at 96 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the healthy participants' arm are positive reaction. | 96 hours after intradermal injection | Yes |
Primary | Number of Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10 | The investigators measure the longitudinal diameter and transverse diameter of induration and/or redness of ESAT6-CFP10 in TB participants at 96 hours after intradermal injection by vernier caliper . And at the same blisters and lymphangitis are the specificity of the positive reaction of ESAT6-CFP10 .So induration ,redness ,blisters and lymphangitis in the participants' arm are positive reaction. | 96 hours after intradermal injection | Yes |
Secondary | the Number of Participants With Adverse Events | evaluate specific time point of vital signs, skin test reaction, blood routine, urine routine, liver and kidney function, electrocardiogram and adverse events as the incidence of adverse events in the participants . Skin test reaction observation time: at the end of the skin test, skin test after 15 minutes, 1 hour, 4 hours, 24 hours, 48 hours, 72 hours, 96 hours; Vital signs evaluation time: 0 minutes before the subjects were intradermal injection, intradermal injection after 15 minutes, 1 hour, 4 hours, 24 hours, 48 hours, 72 hours, 96 hours, 144 hours. Blood routine, urine routine, liver and kidney function, electrocardiogram (ecg) evaluation time: skin test before and 144 h after injection; adverse events evaluation time: participants signed a written informed consent to finish all the follow-up. |
before injection to 144 hours (plus or minus 2 hours) after injection | Yes |
Secondary | the Number of Healthy Participants Negative for IFN-?(Gamma Interferon ) Before Injection | The investigator draw 5ml venous blood for detection of IFN-? four hours before injection with drug.The percentage of negative(negative number/total number*100%) is the specificity of IFN-? in healthy participants. | before injection and after signed ICF(informed consent forms) | No |
Secondary | the Number of Tuberculosis (TB) Participants Positive for IFN-?(Gamma Interferon ) Before Injection | The investigator draw 5ml venous blood for detection of IFN-? four hours before injection with drug. The percentage of positive(positive number/total number*100%) is the sensitivity of IFN-? in TB Participants. | 4 hours before injection and after signed ICF(informed consent forms) | No |
Secondary | the Number of Healthy Participants Negative for IFN-?(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | The investigator draw 5ml venous blood for detection of IFN-? four hours before injection with drug.The percentage of negative(negative number/total number*100%) is the specificity of IFN-? in healthy participants. | 72 hours after injection | No |
Secondary | the Number of Tuberculosis (TB) Participants Positive for IFN-?(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10 | The investigator draw 5ml venous blood for detection of IFN-? 72 hours after injection with drug.The percentage of positive(positivenumber/total number*100%) is the sensitivity of IFN-? in in TB participants. | 72 hours after injection | No |
Secondary | the Number of Healthy Participants Negative for IFN-?(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | The investigator draw 5ml venous blood for detection of IFN-? 144 hours after injection with drug.The percentage of negative(negative number/total number*100%) is the specificity of IFN-? in healthy participants. | 144 hours after injection | No |
Secondary | the Number of Tuberculosis (TB) Participants Positive for IFN-?(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10 | The investigator draw 5ml venous blood for detection of IFN-? 144 hours before injection with drug.The percentage of positive(positive number/total number*100%) is the sensitivity of IFN-? in in TB participants. | 144 hours after injection | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05738681 -
Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial
|
Phase 2/Phase 3 | |
Recruiting |
NCT05526885 -
Tuberculosis Diagnostic Trial of CAD4TB Screening Alone Compared to CAD4TB Screening Combined With a CRP Triage Test, Both Followed by Confirmatory Xpert MTB/RIF Ultra in Communities of Lesotho and South Africa
|
N/A | |
Completed |
NCT04369326 -
Community Initiated Preventive Therapy for TB
|
N/A | |
Recruiting |
NCT04568967 -
TB-CAPT EXULTANT - HIV
|
N/A | |
Completed |
NCT02337270 -
Phase 1 Clinical Trial of the Safety and Immunogenicity of an Adenovirus-based TB Vaccine Administered by Aerosol
|
Phase 1 | |
Not yet recruiting |
NCT06253715 -
Shortened Regimen for Drug-susceptible TB in Children
|
Phase 3 | |
Recruiting |
NCT04271397 -
Immunological Biomarkers in Tuberculosis Management
|
N/A | |
Withdrawn |
NCT03639038 -
Tuberculosis Diagnosis by Flow Cytometry
|
||
Completed |
NCT03199313 -
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid
|
Phase 1 | |
Recruiting |
NCT04975178 -
Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa
|
Phase 3 | |
Completed |
NCT04463680 -
Rifampin and the Contraceptive Implant
|
Phase 4 | |
Completed |
NCT03973970 -
Assessing the Ability of the T-SPOT®.TB Test (IQ)
|
||
Recruiting |
NCT04230395 -
Alcohol Reduction Among People With TB and HIV in India
|
N/A | |
Completed |
NCT04874948 -
Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment
|
Phase 1 | |
Active, not recruiting |
NCT02906007 -
Evaluating the Pharmacokinetics, Safety, and Tolerability of Bedaquiline in Infants, Children, and Adolescents With Multidrug-Resistant Tuberculosis, Living With or Without HIV
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT05917210 -
Peer-led Implementation of TB-HIV Education and Adherence Counseling in Uganda
|
N/A | |
Not yet recruiting |
NCT05845112 -
Start Taking Action For TB Diagnosis
|
||
Not yet recruiting |
NCT06017843 -
Impact Evaluation of Use of MATCH AI Predictive Modelling for Identification of Hotspots for TB Active Case Finding
|
N/A | |
Active, not recruiting |
NCT02715271 -
Study of TB Lesions Obtained in Therapeutical Surgery
|
||
Completed |
NCT02781909 -
Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis
|
Phase 2 |