A Phase Ⅱ Clinical Trial of the Recombinant Mycobacterium Tuberculosis Vaccine Freeze-dried (AEC/BC02)

NCT ID: NCT05284812

Last Updated: 2023-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-10

Study Completion Date

2024-12-31

Brief Summary

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The safety, tolerability and immunogenicity of lyophilized recombinant tuberculosis vaccine (AEC/BC02) were studied in a randomized, blind, controlled phase ⅱ A clinical study in patients 18 years and older with latent infection of Mycobacterium tuberculosis.Twenty patients with negative control group and 180 patients with latent mycobacterium tuberculosis infection were divided into sentinel group, placebo group, high-dose adjuvant group, low-dose vaccine group, high-dose vaccine group and high-dose vaccine group (three doses).During the test, each subject shall not change groups or receive drugs.The negative control group did not take chemical drugs and did not get vaccinated after enrollment, and was only used as immunogenicity control.The latent infection group was given orally Koch inhibitor chemical drugs (Ifu tablet or Ifu capsule) or placebo twice a week, and then received placebo, adjuvant or vaccine every two weeks (0-2-4-6-8-10 weeks), with a total of 6 doses injected intramuscular alternately in the left and right arms of the upper arm deltoid muscle.

Detailed Description

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Conditions

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Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Negative control population group

In population I, 20 subjects were considered to be recombinant mycobacterium tuberculosis fusion protein (EC) and BCG pure protein derivative (BCG-PPD) skin test results were negative.The type I population did not take chemical drugs and was not vaccinated, and was only used as immunogenicity control.

Group Type NO_INTERVENTION

No interventions assigned to this group

Sentinel group

In Population Ⅱ, 20 subjects were considered to be recombinant mycobacterium tuberculosis fusion protein (EC) was positive. First, 5 people aged 18-59 years were selected for low dose injection, 5 people aged 18-59 years were selected for high dose injection, 5 people aged ≥60 years were selected for low dose injection, and 5 people aged ≥60 years were selected for high dose injection.The subjects received a total of 6 doses of the vaccine, 1 dose every 2 weeks.

Group Type OTHER

Low-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Intervention Type BIOLOGICAL

Subjects receive low-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

High-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Intervention Type BIOLOGICAL

Subjects receive high-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

Low-dose group

In population Ⅲ, 40 subjects were considered to be recombinant mycobacterium tuberculosis fusion protein (EC) was positive. The type Ⅲ population were injected Low-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02).The subjects received a total of 6 doses of the vaccine, 1 dose every 2 weeks.

Group Type EXPERIMENTAL

Low-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Intervention Type BIOLOGICAL

Subjects receive low-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

High-dose group

In population Ⅳ, 40 subjects were considered to be recombinant mycobacterium tuberculosis fusion protein (EC) was positive. The type Ⅳ population were injected High-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02).The subjects received a total of 6 doses of the vaccine, 1 dose every 2 weeks.

Group Type EXPERIMENTAL

High-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Intervention Type BIOLOGICAL

Subjects receive high-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

3 dose of High-dose group

In population Ⅴ, 40 subjects were considered to be recombinant mycobacterium tuberculosis fusion protein (EC) was positive. The type Ⅴ population were injected 3 dose of High-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02) and 3 dose of Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo.The first, third, and sixth doses of the subjects were High-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02), and the second, fourth, and fifth doses were Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo. Each dose is 2 weeks apart.

Group Type EXPERIMENTAL

High-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Intervention Type BIOLOGICAL

Subjects receive high-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo

Intervention Type BIOLOGICAL

Subjects receive Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo injection into the deltoid muscle of the upper arm

Placebo group

In population Ⅵ, 20 subjects were considered to be recombinant mycobacterium tuberculosis fusion protein (EC) was positive. The type Ⅵ population were injected Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo.The subjects received a total of 6 doses of the vaccine, 1 dose every 2 weeks.

Group Type PLACEBO_COMPARATOR

Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo

Intervention Type BIOLOGICAL

Subjects receive Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo injection into the deltoid muscle of the upper arm

Adjuvant group

In population Ⅶ, 20 subjects were considered to be recombinant mycobacterium tuberculosis fusion protein (EC) was positive. The type Ⅶ population were injected High-dose adjuvant for freeze-dried recombinant tuberculosis vaccine (AEC / BC02).The subjects received a total of 6 doses of the vaccine, 1 dose every 2 weeks.

Group Type ACTIVE_COMPARATOR

High-dose adjuvant for freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Intervention Type BIOLOGICAL

Subjects receive high-dose adjuvant for freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

Interventions

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Low-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Subjects receive low-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

Intervention Type BIOLOGICAL

High-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Subjects receive high-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

Intervention Type BIOLOGICAL

High-dose adjuvant for freeze-dried recombinant tuberculosis vaccine (AEC / BC02)

Subjects receive high-dose adjuvant for freeze-dried recombinant tuberculosis vaccine (AEC / BC02) injection into the deltoid muscle of the upper arm

Intervention Type BIOLOGICAL

Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo

Subjects receive Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo injection into the deltoid muscle of the upper arm

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. The age is 18 years old and above, and the gender is not limited;
2. I agree to participate in this study and sign the informed consent;
3. I can complete the whole process of clinical research in accordance with the requirements of the clinical research program;
4. Vital signs (reference range of normal values of vital signs: systolic blood pressure \<160 mmHg and diastolic blood pressure \<100 mmHg (which can be controlled by taking medicine), pulse 60-100 beats/min, axillary temperature \<37.3 ℃ in a quiet state), Physical examination results show no abnormality or abnormality without clinical significance;
5. Negative control population: the test results are EC- and PPD- (the average diameter of EC skin test induration and flush is less than 5mm, and the PPD skin test induration is less than 5mm), and the chest imaging is normal;
6. People with latent infection of Mycobacterium tuberculosis: the test result is EC+ (EC skin test induration or flush ≥5mm), and the chest imaging is normal;
7. Laboratory tests including blood routine, urine routine, blood biochemistry and other tests are all normal or have no clinical significance;
8. There is no abnormality in the electrocardiogram examination or the abnormality has no clinical significance;
9. Those who have no history of tuberculosis after medical history inquiry.

Exclusion Criteria

1. Those who are currently diagnosed with tuberculosis or have a history of tuberculosis and/or tuberculosis treatment;
2. There are serious chronic diseases or the disease is in the advanced stage and cannot be controlled smoothly, such as diabetes and thyroid disease;
3. Currently suffering from or within 2 years of any of the following serious diseases, such as: advanced tumor, autoimmune disease, progressive atherosclerosis, acute exacerbation of chronic obstructive pulmonary disease, acute or progressive liver or kidney disease, congestive heart failure exhaustion, etc.;
4. Those with known or suspected (or high-risk) immune function impairments or abnormalities, such as those receiving systemic glucocorticoids, immunosuppressants or immunosuppressants within 3 months, and within 3 months Those who received protein preparations or blood products or plasma extracts outside the gastrointestinal tract;
5. Existing mental/neurological diseases or history of mental/neurological diseases: those with convulsions, epilepsy, encephalopathy, or family history of mental illness;
6. Those who currently suffer from biliary obstruction;
7. People with allergic constitution, such as those with a history of allergy to two or more drugs or foods; a history of severe allergy to any component of the test vaccine, such as: anaphylactic shock, allergic laryngeal edema, allergic purpura, thrombocytopenia Purpura, dyspnea, angioedema, etc.; or a history of the above-mentioned serious side effects after using any vaccine or drug in the past; a history of allergy to isoniazid tablets, rifampicin and rifamycin antibiotics;
8. Patients with severe liver insufficiency, or patients with drug-induced hepatitis and acute liver disease caused by any cause;
9. Difficulty swallowing, active or clinically significant digestive system diseases, and affecting drug absorption;
10. Current patients with active viral hepatitis and/or HIV antibody positive for human immunodeficiency virus and/or current or past syphilis;
11. Women who are pregnant, breastfeeding, or have a positive urine pregnancy test during the screening period, or before vaccination, or who have childbearing plans during the study period;
12. Those who are vaccinated with inactivated vaccine within 14 days before oral administration of chemical drugs, and those who are vaccinated with live attenuated vaccine within 30 days;
13. Those who have participated in any other clinical research and used the investigational drug within 3 months before this clinical research;
14. Any other situation that the researcher believes may affect the evaluation of the research.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tao Huang, Bachelor

Role: PRINCIPAL_INVESTIGATOR

Hunan Provincial Center for Disease Control and Prevention

Locations

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Hunan Provincial Center for Disease Control and Prevention

Changsha, Hunan, China

Site Status

Countries

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China

References

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Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011 Jun;12(6):509-17. doi: 10.1038/ni.2039.

Reference Type BACKGROUND
PMID: 21739679 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20298499 (View on PubMed)

Li J, Fu L, Guo X, Yang Y, Dong J, Wang G, Zhao A. Novel BC02 Compound Adjuvant Enhances Adaptive and Innate Immunity Induced by Recombinant Glycoprotein E of Varicella-Zoster Virus. Vaccines (Basel). 2022 Dec 15;10(12):2155. doi: 10.3390/vaccines10122155.

Reference Type DERIVED
PMID: 36560565 (View on PubMed)

Other Identifiers

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LKM-2021-BJH01

Identifier Type: -

Identifier Source: org_study_id