TuberculosisPhase 2NCT02329730
Phase IIa Clinical Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10
A Phase 2 study testing 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative and 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative in people with Tuberculosis, run by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd..
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative and 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- No sites listed yet
- Study dates
- Feb 2014to Aug 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 to 65 years old
- Consent and signed ICF(informed consent forms)
- Comply with follow-up
- No history or family history of TB(tuberculosis)
- Without the internal and external of pulmonary tuberculosis ; no symptoms of respiratory tract and other body parts for TB
- The examination such as X-ray chest radiograph, sputum bacteria confirmed non-tuberculosis (TB)
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- No uncontrolled kinds of acute or chronic disease or acute infectious diseases or skin disease or skin allergies due to a variety of causes
- 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
- Did not attend any other new drug clinical trials and not vaccinate prevention products and immunoglobulin for nearly 3 months
- Normal axillary temperature(quiet condition ≤37.0 ℃)
- No smoking, no alcohol and drinking caffeinated beverages during the study
- Diagnosis TB according to the health of the People's Republic of China industry standard WS 288-2008 tuberculosis diagnostic criteria
- Aged 18 to 65 years old
- Consent and signed ICF to participate in this study
- Comply with the requirements of the clinical research plan for follow-up
Who cannot join
- 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
- Have seizures, epilepsy, brain and nervous system symptoms or signs of history
- 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
- Has acute febrile diseases and infectious diseases
- Participate in other new drug clinical trials
- Participated in any other new drug clinical trials in 3 months
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- 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
- Women who are in pregnancy or lactation
- People with mental or physical disabilities
- Researchers consider that any conditions may affect the trial evaluation
- 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
- Have seizures, epilepsy, brain and nervous system symptoms or signs of history;
- 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
- People in the pyrogenic stage with febrile diseases or infectious diseases (non tuberculosis)
- Participate in other new drug clinical trials
- Participated in any other new drug clinical trials in 3 months;
- 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;
- Women who are in pregnancy or lactation;
- People with mental or physical disabilities;
- Researchers consider that any conditions may affect the trial evaluation.
About this study
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.
Read the detailed description
First, 56 healthy subjects are distributed into different dose groups according to the recombinant EC allergen dose from low to high.Conducting clinical trials of TB-PPD as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test,after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature), skin reaction at injection site (flush and induration) , local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram (before the skin test,after skin test 144h )are the main test items,Evaluate the safety of the recombinant EC allergy in the expansion of the healthy people , and provide the appropriate dose range for phase IIb clinical trials.
Second,56 patients of TB are distributed different dose groups according to the recombinant EC allergen dose from low to high. Conducting clinical trials of TB-PPD as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test,after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature),skin reaction at injection site (flush and induration) , local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram (before the skin test,after skin test 144h )are the main test items,Evaluate the safety of the recombinant EC allergy in patients of TB,and provide the appropriate dose range for phase IIb clinical trials.
Third,32 patients of TB are distributed into different dose groups according to the recombinant EC allergen dose from low to high. Conducting clinical trials of placebo as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test,after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature), skin reaction at injection site (flush and induration), local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram (before the skin test,after skin test 144h )are the main test items,Evaluate the safety of the recombinant EC allergy in patients of TB on safety.
- Conditions
- Tuberculosis
- Being tested
- 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, 1μg/ml ESAT6-CFP10 and placebo
- Keywords
- diagnosis of Tuberculosis (TB), ESAT6, CFP10, Phase IIa Clinical Trial
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeBiological
Also called Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPD
Left arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 1μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively.
5μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeBiological
Also called Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10/TB-PPD
Left arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 5g/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively.
10μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeBiological
Also called Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPD
Left arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 10g/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively.
20μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeBiological
Also called Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPD
Left arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 20/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively.
1μg/ml ESAT6-CFP10 and placeboBiological
Also called Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10
Left arm intradermal injection of the placebo of 1μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 1μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects.
5μg/ml ESAT6-CFP10 and placeboBiological
Also called Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10
Left arm intradermal injection of the placebo of 5μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 5μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects.
10μg/ml ESAT6-CFP10 and placeboBiological
Also called Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10
Left arm intradermal injection of the placebo of 10μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 10μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects.
20μg/ml ESAT6-CFP10 and placeboBiological
Also called Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10
Left arm intradermal injection of the placebo of 20μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 20μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects.
| Study group | Role | What they receive |
|---|---|---|
| the healthy subjects | Experimental | The healthy subjects inject 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time .Right arm inject ESAT6-CFP10 and left arm inject tuberculin purified protein derivative. Two drugs must be use in the same subjects. Receives: Biological: 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative |
| the first part of tuberculosis subjects | Experimental | The first part kind of tuberculosis subjects inject 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time .Right arm inject ESAT6-CFP10 and left arm inject tuberculin purified protein derivative. Two drugs must be use in the same subjects. Receives: Biological: 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative; Biological: 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative |
| the second part of tuberculosis subjects | Experimental | The second part of tuberculosis subjects inject 1μg/ml ESAT6-CFP10 and placebo only one time , or 5μg/ml ESAT6-CFP10 and placebo only one time , or 10μg/ml ESAT6-CFP10 and placebo only one time , or 20μg/ml ESAT6-CFP10 and placebo only one time .Right arm inject ESAT6-CFP10 and left arm inject placebo. Two drugs must be use in the same subjects. Receives: Biological: 1μg/ml ESAT6-CFP10 and placebo; Biological: 5μg/ml ESAT6-CFP10 and placebo; Biological: 10μg/ml ESAT6-CFP10 and placebo; Biological: 20μg/ml ESAT6-CFP10 and placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 .
Measured: 24 hours after intradermal injection
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.
Measured: 24 hours after intradermal injection
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.
Measured: 48 hours after intradermal injection
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.
Measured: 48 hours after intradermal injection
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
Measured: 72 hours after intradermal injection
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.
Measured: 72 hours after intradermal injection
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.
Measured: 96 hours after intradermal injection
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.
Measured: 96 hours after intradermal injection
Secondary outcomes (7)
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.
Measured: before injection to 144 hours (plus or minus 2 hours) after injection
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection
The investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug.The percentage of negative(negative number/total number*100%) is the specificity of IFN-γ in healthy participants.
Measured: before injection and after signed ICF(informed consent forms)
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) Before Injection
The investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug. The percentage of positive(positive number/total number*100%) is the sensitivity of IFN-γ in TB Participants.
Measured: 4 hours before injection and after signed ICF(informed consent forms)
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10
The investigator draw 5ml venous blood for detection of IFN-γ four hours before injection with drug.The percentage of negative(negative number/total number*100%) is the specificity of IFN-γ in healthy participants.
Measured: 72 hours after injection
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10
The investigator draw 5ml venous blood for detection of IFN-γ 72 hours after injection with drug.The percentage of positive(positivenumber/total number*100%) is the sensitivity of IFN-γ in in TB participants.
Measured: 72 hours after injection
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10
The investigator draw 5ml venous blood for detection of IFN-γ 144 hours after injection with drug.The percentage of negative(negative number/total number*100%) is the specificity of IFN-γ in healthy participants.
Measured: 144 hours after injection
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10
The investigator draw 5ml venous blood for detection of IFN-γ 144 hours before injection with drug.The percentage of positive(positive number/total number*100%) is the sensitivity of IFN-γ in in TB participants.
Measured: 144 hours after injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2015 (estimated)
- Study startFeb 2014
- Primary completionJun 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Shanghai Public Health Clinical Center, Tianjin Haihe Hospital, Air Force Military Medical University, China, Proswell Medical Corporation
- Responsible party
- Sponsor
- Investigators
- Shuihua Lu, Bachelor, Principal investigator, Shanghai Public Health Clinical CenterQi Wu, Master, Principal investigator, Tianjin Haihe Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02329730
- Sponsor's protocol ID
- LTao-EC IIa
- Status last verified
- Mar 2015
- First submitted
- 23 Dec 2014
- Last updated
- 9 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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. doi: 10.1128/CDLI.7.2.155-160.2000.
PubMed 10702486Ravn 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. doi: 10.1128/CDLI.12.4.491-496.2005.
PubMed 15817755Brusasca 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. doi: 10.1046/j.1365-3083.2001.00975.x.
PubMed 11696195Weldingh 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.
PubMed 18431468Aagaard C, Govaerts M, Meikle V, Vallecillo AJ, Gutierrez-Pabello JA, Suarez-Guemes 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. doi: 10.1128/JCM.01184-06. Epub 2006 Sep 27.
PubMed 17005738
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIa Clinical Study of Recombinant Mycobacterium Tuberculosis Antigen ESAT6-CFP10
- ClinicalTrials.gov ID
- NCT02329730
- Acronym / sponsor ID
- LTao-EC IIa
- Conditions
- Tuberculosis
- Keywords
- diagnosis of Tuberculosis (TB), ESAT6, CFP10, Phase IIa Clinical Trial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Shanghai Public Health Clinical Center, Tianjin Haihe Hospital, Air Force Military Medical University, China, Proswell Medical Corporation
- Study start
- Feb 2014
- Primary completion
- Jun 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 1 Jan 2015 (estimated)
- Results
- Posted 9 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
First, 56 healthy subjects are distributed into different dose groups according to the recombinant EC allergen dose from low to high.Conducting clinical trials of TB-PPD as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test,after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature), skin reaction at injection site (flush and induration) , local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram (before the skin test,after skin test 144h )are the main test items,Evaluate the safety of the recombinant EC allergy in the expansion of the healthy people , and provide the appropriate dose range for phase IIb clinical trials.
Second,56 patients of TB are distributed different dose groups according to the recombinant EC allergen dose from low to high. Conducting clinical trials of TB-PPD as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test,after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature),skin reaction at injection site (flush and induration) , local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram (before the skin test,after skin test 144h )are the main test items,Evaluate the safety of the recombinant EC allergy in patients of TB,and provide the appropriate dose range for phase IIb clinical trials.
Third,32 patients of TB are distributed into different dose groups according to the recombinant EC allergen dose from low to high. Conducting clinical trials of placebo as controlled arms intradermal injection.Do specific interferon gamma detection before the skin test,after the test 72h±2h and 144h±2h. The vital signs (breathing, heart rate, blood pressure and temperature), skin reaction at injection site (flush and induration), local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events; The vital signs, blood routine, urine routine, liver and kidney function, electrocardiogram (before the skin test,after skin test 144h )are the main test items,Evaluate the safety of the recombinant EC allergy in patients of TB on safety.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| the healthy subjects | Experimental | Biological: 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, Biological: 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, Biological: 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, Biological: 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeThe healthy subjects inject 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time .Right arm inject ESAT6-CFP10 and left arm inject tuberculin purified protein derivative. Two drugs must be use in the same subjects. |
| the first part of tuberculosis subjects | Experimental | Biological: 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, Biological: 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, Biological: 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, Biological: 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeThe first part kind of tuberculosis subjects inject 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time , or 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivative only one time .Right arm inject ESAT6-CFP10 and left arm inject tuberculin purified protein derivative. Two drugs must be use in the same subjects. |
| the second part of tuberculosis subjects | Experimental | Biological: 1μg/ml ESAT6-CFP10 and placebo, Biological: 5μg/ml ESAT6-CFP10 and placebo, Biological: 10μg/ml ESAT6-CFP10 and placebo, Biological: 20μg/ml ESAT6-CFP10 and placeboThe second part of tuberculosis subjects inject 1μg/ml ESAT6-CFP10 and placebo only one time , or 5μg/ml ESAT6-CFP10 and placebo only one time , or 10μg/ml ESAT6-CFP10 and placebo only one time , or 20μg/ml ESAT6-CFP10 and placebo only one time .Right arm inject ESAT6-CFP10 and left arm inject placebo. Two drugs must be use in the same subjects. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 18 to 65 years old
- Consent and signed ICF(informed consent forms)
- Comply with follow-up
- No history or family history of TB(tuberculosis)
- Without the internal and external of pulmonary tuberculosis ; no symptoms of respiratory tract and other body parts for TB
Key exclusion criteria (20 listed)
- 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
- Have seizures, epilepsy, brain and nervous system symptoms or signs of history
- 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
- Has acute febrile diseases and infectious diseases
- Participate in other new drug clinical trials
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeAlso: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPDLeft arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 1μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively. | Biological | the first part of tuberculosis subjects, the healthy subjects |
| 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeAlso: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10/TB-PPDLeft arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 5g/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively. | Biological | the first part of tuberculosis subjects, the healthy subjects |
| 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeAlso: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPDLeft arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 10g/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively. | Biological | the first part of tuberculosis subjects, the healthy subjects |
| 20μg/ml ESAT6-CFP10 and tuberculin purified protein derivativeAlso: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 /TB-PPDLeft arm intradermal injection of 0.1ml TB-PPD(50IU/ml) by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 20/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 Allergen and TB-PPD only one time in the healthy subjects and the first part of tuberculosis subjects respectively. | Biological | the first part of tuberculosis subjects, the healthy subjects |
| 1μg/ml ESAT6-CFP10 and placeboAlso: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10Left arm intradermal injection of the placebo of 1μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 1μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects. | Biological | the second part of tuberculosis subjects |
| 5μg/ml ESAT6-CFP10 and placeboAlso: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10Left arm intradermal injection of the placebo of 5μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 5μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects. | Biological | the second part of tuberculosis subjects |
| 10μg/ml ESAT6-CFP10 and placeboAlso: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10Left arm intradermal injection of the placebo of 10μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 10μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects. | Biological | the second part of tuberculosis subjects |
| 20μg/ml ESAT6-CFP10 and placeboAlso: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10Left arm intradermal injection of the placebo of 20μg/ml ESAT6-CFP10 by a syringe(1ml).Observe 30 minutes , if without obvious adverse reaction then right arm intradermal injection 20μg/ml ESAT6-CFP10 by a syringe(1ml). Inject ESAT6-CFP10 and placebo only one time in the second part of tuberculosis subjects. | Biological | the second part of tuberculosis subjects |
Primary outcome
Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 24 hours after intradermal injection
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 .
Number of Tuberculosis (TB) Participants Positive for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 24 hours after intradermal injection
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.
Number of Healthy Participants Negative for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 48 hours after intradermal injection
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.
Number of Tuberculosis (TB) Participants Positive for Reaction at 48 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 48 hours after intradermal injection
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.
Number of Healthy Participants Negative for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 72 hours after intradermal injection
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
Number of Tuberculosis (TB) Participants Positive for Reaction at 72 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 72 hours after intradermal injection
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.
Number of Healthy Participants Negative for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 96 hours after intradermal injection
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.
Number of Tuberculosis (TB) Participants Positive for Reaction at 96 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 96 hours after intradermal injection
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.
7 secondary outcomes
the Number of Participants With Adverse Events
Time frame: before injection to 144 hours (plus or minus 2 hours) after injection
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) Before Injection
Time frame: before injection and after signed ICF(informed consent forms)
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) Before Injection
Time frame: 4 hours before injection and after signed ICF(informed consent forms)
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 72 hours after injection
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 72 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 72 hours after injection
the Number of Healthy Participants Negative for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 144 hours after injection
the Number of Tuberculosis (TB) Participants Positive for IFN-γ(Gamma Interferon ) at 144 Hours After Intradermal Injection With ESAT6-CFP10
Time frame: 144 hours after injection
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10702486van 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. doi: 10.1128/CDLI.7.2.155-160.2000.
- Background: PubMed 15817755Ravn 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. doi: 10.1128/CDLI.12.4.491-496.2005.
- Background: PubMed 11696195Brusasca 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. doi: 10.1046/j.1365-3083.2001.00975.x.
- Background: PubMed 18431468Weldingh 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.
- Background: PubMed 17005738Aagaard C, Govaerts M, Meikle V, Vallecillo AJ, Gutierrez-Pabello JA, Suarez-Guemes 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. doi: 10.1128/JCM.01184-06. Epub 2006 Sep 27.
- Center for drug evaluation, CFDA ,ChinaLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shuihua Lu, Bachelor principal investigator
Shanghai Public Health Clinical Center
Qi Wu, Master principal investigator
Tianjin Haihe Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 1μg/ml ESAT6-CFP10 and tuberculin purified protein derivative, 5μg/ml ESAT6-CFP10 and tuberculin purified protein derivative and 10μg/ml ESAT6-CFP10 and tuberculin purified protein derivative in people with Tuberculosis, run by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Healthy Participants Negative for Reaction at 24 Hours After Intradermal Injection With ESAT6-CFP10 (time frame: 24 hours after intradermal injection). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02329730, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2015.