Phase I Clinical Human Tolerability Study of Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10

NCT01999231 | Completed Phase 1 Results

• 2 other identifiers: LTao-ECLTao
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

In the tests, small sample of clinical study about Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10 ( Recombination EC Allergen） healthy adults was carried out. 24 healthy adults were included as study objects, they were randomly divided into four groups of different Recombinant Allergen EC dose (1, 5, 10μg/mL, maximum tolerated dose 20μg/mL, 6 person/dose) for single arm intradermal injection. The main examination items :vital signs (breathing, heart rate, blood pressure, body temperature ) of each volunteer at 15min, 30min, 1h, 2h, 4h, 8h, 24h, 48h, 72h, 96h after injection, skin reactivity (redness and/or induration) diameter of injection sites,local reaction ( rash, pain, itching, and skin and mucous membranes ) ,a variety of adverse events,routine blood,routine urine, liver and kidney function, ECG and chest X-ray films before and 7 days after intradermal injection . Preliminary evaluation of safety and tolerability of Recombinant Allergen EC applied in humans, which can provide a safe dosage range for phase II clinical study.

Conditions

Healthy

Keywords

Safety; Tolerability; ESAT6; CFP10; skin test; diagnostic test

Outcome Measures

Primary Outcomes (1)

• the Cases of Adverse Events With Participant Injection of ESAT6-CFP10

  The main examination items :vital signs (breathing, heart rate, blood pressure, body temperature ) of each volunteer at 15min, 30min, 1h, 2h, 4h, 8h, 24h, 48h, 72h, 96h after injection, skin reactivity (redness and/or induration) of injection sites,local reaction ( rash, pain, itching, and skin mucous membranes ) ,a variety of adverse events,routine blood,routine urine, liver and kidney function, ECG and chest X-ray films before and 7 days after intradermal injection .

  within 7 days after the injections

Secondary Outcomes (5)

• the Number of Participants Who Appear the Induration and/or Redness 2h After Application of ESAT6-CFP10

  within 2h after application of ESAT6-CFP10

• the Number of Participants Who Appear the Induration and/or Redness 24h After Application of ESAT6-CFP10

  24h after application of ESAT6-CFP10

• the Number of Participants Who Appear the Induration and/or Redness 48h After Application of ESAT6-CFP10

  48h after application of ESAT6-CFP10

• the Number of Participants Who Appear the Induration and/or Redness 72h After Application of ESAT6-CFP10

  72h after application of ESAT6-CFP10

• the Number of Participants Who Appear the Induration and/or Redness 96h After Application of ESAT6-CFP10

  96h after application of ESAT6-CFP10

Study Arms (4)

1μg/ml ESAT6-CFP10

EXPERIMENTAL

The 1μg/ml ESAT6-CFP10 is given 0.1ml alone to volunteers in the RIGHT or LEFT forearm according to a randomisation scheme.

Biological: ESAT6-CFP10

5μg/ml ESAT6-CFP10

EXPERIMENTAL

The 5μg/ml ESAT6-CFP10 is given 0.1ml alone to volunteers in the RIGHT or LEFT forearm according to a randomisation scheme.

Biological: ESAT6-CFP10

10μg/ml ESAT6-CFP10

EXPERIMENTAL

The 10μg/ml ESAT6-CFP10 is given 0.1ml alone to volunteers in the RIGHT or LEFT forearm according to a randomisation scheme.

Biological: ESAT6-CFP10

20μg/ml ESAT6-CFP10

EXPERIMENTAL

The 20μg/ml ESAT6-CFP10 is given 0.1ml alone to volunteers in the RIGHT or LEFT forearm according to a randomisation scheme.

Biological: ESAT6-CFP10

Interventions

ESAT6-CFP10 BIOLOGICAL

32 healthy subjects who meet the standard of protocol are allocated four different groups according to dosages of ESAT6-CFP10 :1μg/ml ESAT6-CFP10、5μg/ml ESAT6-CFP10、10μg/ml ESAT6-CFP10、20μg/ml ESAT6-CFP10.Each dose group have six healthy subjects(three male and three female) , at the same time set up two people for substitute (one male and one female) . ESAT6-CFP10 administered intradermally by the mantoux injection technique. Each receives only one dosage in right or left arm .

Also known as: Recombinant Mycobacterium Tuberculosis Allergen ESAT6-CFP10, EC

10μg/ml ESAT6-CFP10; 1μg/ml ESAT6-CFP10; 20μg/ml ESAT6-CFP10; 5μg/ml ESAT6-CFP10

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged from 18 to 40 years old, age difference is not more than 10 years old within the same batch of healthy volunteers, the male to female ratio of cases is 1:1. Body mass index should be in the range of 20 to 27 Body Mass Index BMI: weight (Kg)/ height (M2);
• Agreed to participate in the test and sign the informed consent;
• Subjects should comply with the requirements of the clinical trial protocol and be followed;
• Subjects have no history of TB (Tuberculosis)or family history of tuberculosis;
• People have no pulmonary tuberculosis or extrapulmonary tuberculosis,respiratory symptom or systemic symptoms;
• People have no tuberculosis focus after examination by X-ray chest radiograph and sputum bacilli;
• Subjects have no acute or chronic disease, acute infectious diseases, dermatoses or skin allergy caused by various reasons;
• Physical condition: have no history of heart, liver, kidney, gastrointestinal tract, nervous system, or metabolic disturbance, etc. ECG, blood pressure, heart rate, respiratory status and lab test indexes including blood, urine, liver and kidney function, etc are all normal within 4 weeks before screening;
• No close contacts of tuberculosis;
• Subjects have not participated in other clinical drug trials or inoculated against other prophylactic and immune globulin in the nearly 3 months;
• Temperature is normal;
• Stop smoking, drinking and drinking contains caffeinated.

You may not qualify if:

• Health people have close contacts of TB (Tuberculosis)patients, especially excreter in 3 weeks before selection;
• Suffering from any other serious disease, e.g. during cancer treatment, autoimmune disease, progressive atherosclerosis, diabetes accompanied with complications, chronic obstructive pulmonary disease (COPD) needing oxygen therapy, acute or progressive liver or kidney disease, congestive heart failure, etc.;
• People have history of allergy, convulsions, epilepsy, cerebropathy, neurological symptoms and signs;
• Patients who have impaired or abnormal immune function, e.g. patients treated with immunosuppressor or immunopotentiator, received immunoglobulin preparation or blood products or plasma extraction outside the gastrointestinal tract in 3 months, human immunodeficiency virus or related diseases;
• Acute febrile illness and infection;
• Taking part in other clinic trials;
• Subjects have participated in any other clinical drug trials in 3 months before our clinical tests;
• Allergic constitution, e.g. patients have allergic history to two or more kinds of drugs or food, or drug components;
• Substance abuse and alcoholics ;
• Pregnant or breast feeding women;
• Mental or physical disability;
• Informed leavers;
• Any other cases that may influence the test evaluation.

Sponsors & Collaborators

• Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.: lead
• Shanghai Public Health Clinical Center: collaborator
• Air Force Military Medical University, China: collaborator
• Proswell Medical Corporation: collaborator

Related Publications (6)

• 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.

  PMID: 10702486 BACKGROUND

• 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. doi: 10.1128/CDLI.12.4.491-496.2005.

  PMID: 15817755 BACKGROUND

• 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. doi: 10.1046/j.1365-3083.2001.00975.x.

  PMID: 11696195 BACKGROUND

• 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.

  PMID: 18431468 BACKGROUND

• Aagaard 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.

  PMID: 17005738 BACKGROUND

• Li F, Xu M, Zhou L, Xiong Y, Xia L, Fan X, Gu J, Pu J, Lu S, Wang G. Safety of Recombinant Fusion Protein ESAT6-CFP10 as a Skin Test Reagent for Tuberculosis Diagnosis: an Open-Label, Randomized, Single-Center Phase I Clinical Trial. Clin Vaccine Immunol. 2016 Sep 6;23(9):767-73. doi: 10.1128/CVI.00154-16. Print 2016 Sep.

  PMID: 27413070 DERIVED

Related Links

• Center for drug evaluation, CFDA ,China

MeSH Terms

Interventions

ESAT-6-CFP10 fusion protein

Limitations and Caveats

If the operator don't have standard measurement of transverse diameter and the vertical diameter of induration or redness ,we get unreliable data .The participant lost any follow-up will lead to small numbers of subjects analyzed.

Results Point of Contact

• Title: Shuihua Lu
• Organization: Shanghai Public Health Clinical Center

tubercle@gmail.com

(+86)18930811818

Study Officials

• Shuihua Lu, Bachelor

  Shanghai Public Health Clinical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2013
• First Posted: December 3, 2013
• Study Start: September 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 31, 2015
• Results First Posted: March 31, 2015

Record last verified: 2015-03