Tuberculosis Clinical Trial
— AEC/BC02Official title:
A Phase ⅠStudy of the Human Body Tolerance Research of the Recombinant Mycobacterium Tuberculosis Vaccine Freeze-dried
Verified date | December 2019 |
Source | Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
There are four populations in Recombinant Mycobacterium tuberculosis Vaccine Freeze-dried (AEC/BC02) phase I clinical research. The clinical study adopt open research design. Population I have 25 subjects who received Tuberculin purified protein derivative(TB-PPD) skin test and specific gamma-interferon (γ-IFN)detection whose results are both negative ;Population II have 30 subjects who received Tuberculin purified protein derivative(TB-PPD) and ESAT6-CFP10 skin test in different arms , specific gamma-interferon (γ-IFN) detection whose results are all negative.We call polulation III as uninfected TB PPD positve population.This group screened 30 subjects whose ESAT6-CFP10 skin test and specific gamma-interferon (γ-IFN)detection results are both negative,but Tuberculin purified protein derivative(TB-PPD) skin test positive.50 subjects whose three kinds of detection results are all positive γ-IFN,TB-PPD and ESAT6-CFP10 ) are named as population IV. After filtrating, injecting of population I start firstly.After ensure the safety of the population I,the population II~polulation IV carry out in turn the implementation at the same time.
Status | Completed |
Enrollment | 25 |
Est. completion date | October 30, 2019 |
Est. primary completion date | September 4, 2018 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 45 Years |
Eligibility | Inclusion Criteria: - 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; - Aged form 18-45 years old . Body mass index should be in the range of 18-30. Body Mass Index BMI: weight (Kg)/ [height (m)*height (m)]; - Physical condition: body temperatue, blood pressure, heart rate and respiratory status are normal minor abnormalities but no abnormal symptoms and signs; - Lab test including blood, urine, liver and kidney function are normal minor abnormalities but no abnormal symptoms and signs; - ECG,X-ray chest radiograph are normal minor abnormalities but no abnormal symptoms and signs; - Subjects have no history of tuberculosis; - Subjects have no acute or chronic disease, acute infectious diseases, dermatoses or skin allergy caused by various reasons; - Subject have not participated in other clinical drug trials or inoculated against other prophylactic and immune globulin in the nearly 3 months. Exclusion Criteria: - Suffering from other serious disease, e.g. tumor, 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; - Subjects were a history of TB; - Subjects are immune dysfunction or abnormal, e.g. patients receive immunosuppressive agents or immunosuppressive agents, receive immunoglobulin preparations outsider the gastrointestinal or blood products within 3 months, extracted plasma or infected by immunodeficiency virus or related disease; - Mentally or physically disabled,and have family history of convulsions, epilepsy, encephalopathy or mental illness. - Subjects have took part in other clinical trials in the nearly 3 months,or vacinated any prophylactic; - Allergic constitution, e.g. patients have allergic history to two or more kinds of drugs or food, or drug components; - Substance abuse, drug or alcohol abuse; - Pregnant or breast feeding female; - people have birth plan during study or in six moons after entire immune; - Any other cases that may influence the test evaluation. |
Country | Name | City | State |
---|---|---|---|
China | Shanghai Public Health clinical Center | Shanghai | Shanghai |
Lead Sponsor | Collaborator |
---|---|
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. | Beijing Simoonrecord Pharmaceutical Information Consulting Co.,Ltd, Shanghai Public Health Clinical Center |
China,
Alexander DC, Liu J. Mycobacteria Genomes. Bacterial Genomes and InfecDis.2003,7(2):153-154.
Andersen P, Doherty TM. TB subunit vaccines--putting the pieces together. Microbes Infect. 2005 May;7(5-6):911-21. Epub 2005 Apr 14. Review. — View Citation
Brandt L, Feino Cunha J, Weinreich Olsen A, Chilima B, Hirsch P, Appelberg R, Andersen P. Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis. Infect Immun. 2002 Feb;70(2):672-8. — View Citation
Chen L, Xu M, Wang ZY, Chen BW, Du WX, Su C, Shen XB, Zhao AH, Dong N, Wang YJ, Wang GZ. The development and preliminary evaluation of a new Mycobacterium tuberculosis vaccine comprising Ag85b, HspX and CFP-10:ESAT-6 fusion protein with CpG DNA and aluminum hydroxide adjuvants. FEMS Immunol Med Microbiol. 2010 Jun 1;59(1):42-52. doi: 10.1111/j.1574-695X.2010.00660.x. Epub 2010 Feb 17. — View Citation
Cooper CL, Davis HL, Morris ML, Efler SM, Krieg AM, Li Y, Laframboise C, Al Adhami MJ, Khaliq Y, Seguin I, Cameron DW. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine. 2004 Aug 13;22(23-24):3136-43. — View Citation
Didierlaurent AM, Morel S, Lockman L, Giannini SL, Bisteau M, Carlsen H, Kielland A, Vosters O, Vanderheyde N, Schiavetti F, Larocque D, Van Mechelen M, Garçon N. AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. J Immunol. 2009 Nov 15;183(10):6186-97. doi: 10.4049/jimmunol.0901474. Epub 2009 Oct 28. — View Citation
Halperin SA, Van Nest G, Smith B, Abtahi S, Whiley H, Eiden JJ. A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant. Vaccine. 2003 Jun 2;21(19-20):2461-7. — View Citation
He Q, Mitchell A, Morcol T, Bell SJ. Calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type 2. Clin Diagn Lab Immunol. 2002 Sep;9(5):1021-4. — View Citation
Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdörfer B, Giese T, Endres S, Hartmann G. Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol. 2002 May 1;168(9):4531-7. — View Citation
Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med. 2004 May 13;350(20):2060-7. — View Citation
Jones TR, Obaldia N 3rd, Gramzinski RA, Charoenvit Y, Kolodny N, Kitov S, Davis HL, Krieg AM, Hoffman SL. Synthetic oligodeoxynucleotides containing CpG motifs enhance immunogenicity of a peptide malaria vaccine in Aotus monkeys. Vaccine. 1999 Aug 6;17(23-24):3065-71. — View Citation
Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature. 1995 Apr 6;374(6522):546-9. — View Citation
Lalvani A, Nagvenkar P, Udwadia Z, Pathan AA, Wilkinson KA, Shastri JS, Ewer K, Hill AV, Mehta A, Rodrigues C. Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. J Infect Dis. 2001 Feb 1;183(3):469-77. Epub 2000 Dec 21. — View Citation
McShane H, Hill A. Prime-boost immunisation strategies for tuberculosis. Microbes Infect. 2005 May;7(5-6):962-7. Epub 2005 Apr 15. Review. — View Citation
Mostowy S, Cousins D, Brinkman J, Aranaz A, Behr MA. Genomic deletions suggest a phylogeny for the Mycobacterium tuberculosis complex. J Infect Dis. 2002 Jul 1;186(1):74-80. Epub 2002 May 30. — View Citation
Mostowy S, Onipede A, Gagneux S, Niemann S, Kremer K, Desmond EP, Kato-Maeda M, Behr M. Genomic analysis distinguishes Mycobacterium africanum. J Clin Microbiol. 2004 Aug;42(8):3594-9. — View Citation
Murray JF. [Current clinical manifestations of tuberculosis]. Rev Prat. 1996 Jun 1;46(11):1344-9. French. — View Citation
Olsen AW, Williams A, Okkels LM, Hatch G, Andersen P. Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT-6 in the aerosol guinea pig model. Infect Immun. 2004 Oct;72(10):6148-50. — View Citation
Pathan AA, Wilkinson KA, Klenerman P, McShane H, Davidson RN, Pasvol G, Hill AV, Lalvani A. Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. J Immunol. 2001 Nov 1;167(9):5217-25. — View Citation
Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011 Jun;12(6):509-17. Review. — View Citation
Stewart VA, McGrath S, Krieg AM, Larson NS, Angov E, Smith CL, Brewer TG, Heppner DG Jr. Activation of innate immunity in healthy Macaca mulatta macaques by a single subcutaneous dose of GMP CpG 7909: safety data and interferon-inducible protein-10 kinetics for humans and macaques. Clin Vaccine Immunol. 2008 Feb;15(2):221-6. Epub 2007 Dec 12. — View Citation
Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 2):S221-47. Review. — View Citation
Taylor JL, Turner OC, Basaraba RJ, Belisle JT, Huygen K, Orme IM. Pulmonary necrosis resulting from DNA vaccination against tuberculosis. Infect Immun. 2003 Apr;71(4):2192-8. — View Citation
Taylor Z, Nolan CM, Blumberg HM; American Thoracic Society; Centers for Disease Control and Prevention; Infectious Diseases Society of America. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2005 Nov 4;54(RR-12):1-81. Erratum in: MMWR Morb Mortal Wkly Rep. 2005 Nov 18;54(45):1161. — View Citation
Thomas LJ, Hammond RA, Forsberg EM, Geoghegan-Barek KM, Karalius BH, Marsh HC Jr, Rittershaus CW. Co-administration of a CpG adjuvant (VaxImmune, CPG 7909) with CETP vaccines increased immunogenicity in rabbits and mice. Hum Vaccin. 2009 Feb;5(2):79-84. Epub 2009 Mar 1. — View Citation
Tokunaga T, Yamamoto H, Shimada S, Abe H, Fukuda T, Fujisawa Y, Furutani Y, Yano O, Kataoka T, Sudo T, et al. Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity. J Natl Cancer Inst. 1984 Apr;72(4):955-62. — View Citation
Torres M, Herrera T, Villareal H, Rich EA, Sada E. Cytokine profiles for peripheral blood lymphocytes from patients with active pulmonary tuberculosis and healthy household contacts in response to the 30-kilodalton antigen of Mycobacterium tuberculosis. Infect Immun. 1998 Jan;66(1):176-80. — View Citation
Turner OC, Roberts AD, Frank AA, Phalen SW, McMurray DM, Content J, Denis O, D'Souza S, Tanghe A, Huygen K, Orme IM. Lack of protection in mice and necrotizing bronchointerstitial pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis. Infect Immun. 2000 Jun;68(6):3674-9. — View Citation
Tyagi AK, Nangpal P, Satchidanandam V. Development of vaccines against tuberculosis. Tuberculosis (Edinb). 2011 Sep;91(5):469-78. doi: 10.1016/j.tube.2011.01.003. Epub 2011 Feb 18. Review. — View Citation
Vollmer J, Krieg AM. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv Drug Deliv Rev. 2009 Mar 28;61(3):195-204. doi: 10.1016/j.addr.2008.12.008. Epub 2009 Jan 13. Review. — View Citation
Weeratna RD, McCluskie MJ, Xu Y, Davis HL. CpG DNA induces stronger immune responses with less toxicity than other adjuvants. Vaccine. 2000 Mar 6;18(17):1755-62. — View Citation
Young D, Dye C. The development and impact of tuberculosis vaccines. Cell. 2006 Feb 24;124(4):683-7. — View Citation
* Note: There are 32 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The number of participants with Adverse Events after coxal muscle injection | The adverse events observed mainly from laboratory examination(including vital signs/routine blood/routingurine/Liver and kidney fuction/Electrocardiograghy and Chest X-ray detection),skin reactivity and local reaction after drug injection.Vital signs(breathing,pulse,blood pressure,body temperature) of each volunteer before each dose injection,and 30min after injection.Routine blood,routine urine,liver and kidney function,and ECG before first dose,third dose,sixth dose,and 7 days after the sixth time injection;skin reactivity and local reaction of rach volunteer at 30min before and after every injection. | Up to a week after the sixth time injection | |
Secondary | Laboratory markers of immunity | Evaluation of IFN-?and antibody level of before and after the immune,intracellular cytokine staining in blood . | Up to a week after the sixth time injection |
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 |
NCT06017843 -
Impact Evaluation of Use of MATCH AI Predictive Modelling for Identification of Hotspots for TB Active Case Finding
|
N/A | |
Not yet recruiting |
NCT05845112 -
Start Taking Action For TB Diagnosis
|
||
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 |