Clinical trial NCT05680415: Clinical Trial of Mica
Official title: Phase IV Clinical Trial of the Safety, Efficacy, and Immunogenicity of Mycobacterium Vaccae for Injection (Mica) in People Over 15 Years of Age With Latent Mycobacterium Tuberculosis Infection
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Latent Tuberculosis Infection
Lead sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-11
Enrollment: 6800
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The experimental group and the blank control group were randomly assigned in a ratio of 1:1.
Primary purpose: PREVENTION

Brief summary: This study used a randomized, open, blank control design. A total of 6800 patients over 15 years old with latent mycobacterium tuberculosis infection who met the inclusion criteria but did not meet the exclusion criteria were randomly assigned to the experimental group and the blank control group in a 1:1 ratio, with 3400 patients in each group. The experimental group was alternately injected with 1 dose of microcard every two weeks (0-2-4-6-8-10 weeks) in the left and right hip muscle deep, with a total of 6 doses. The blank control group was not injected with drugs.

Detailed description: 1. Effectiveness evaluation

   Chest imaging examinations were performed at 6, 12, 18 and 24 months after full injection. The blank control group underwent chest imaging examination at 6, 12, 18 and 24 months after 10 weeks. The confirmed and clinically diagnosed cases of tuberculosis in the experimental group were collected from the first dose to 24 months after full injection and the blank control group from 24 months +10 weeks after enrollment. Follow-up is completed if 8 confirmed cases have been collected after 24 months. If no cases are collected within 24 months, follow-up is required until 8 confirmed cases are collected, and follow-up after 24 months only requires chest imaging every 6 months.
2. Safety evaluation

   In the experimental group, AE was collected 30 minutes after each dose, AE was collected from the first dose to 30 days after the full dose, and SAE and AESI (including immune system related diseases such as thyroid/parathyroid disease) from the first dose to 6 months after the full dose. All pregnancy events from the first dose to 30 days after the full dose were collected.

   In the control group, only all AESI (including immune system related diseases such as thyroid/parathyroid diseases) were collected up to 10 weeks and 6 months of enrollment.

   The test group underwent thyroid palpation examination before injection and 6 months after injection. The blank control group underwent thyroid palpation examination on the day of enrollment, 10 weeks and 6 months after enrollment. Cervical ultrasound examination and five tests of thyroid function were added if there were abnormal thyroid palpation in the experimental group at 6 months after full injection and the blank control group at 10 weeks +6 months.
3. Immunogenicity evaluation

Blood samples of the first 100 subjects in the experimental group and the control group were collected for immunogenicity evaluation, which included cellular immunity and humoral immunity. The first 25 subjects in each group were tested for the absolute number of total white blood cells and specific T cells per unit volume of blood. Blood collection time points: 1 month and 12 months before the first dose of the experimental group was injected; The blank control group was the day of enrollment, 1 month +10 weeks and 12 months +10 weeks after enrollment.

Eligibility criteria: Inclusion Criteria:

1. Age 15 and above (≥15 years old), gender unlimited;
2. I (and my guardian) agree to participate in this study and sign the informed consent, willing and able to comply with the requirements of the clinical study protocol;
3. Patients with normal body temperature (axillary temperature \< 37.3℃);
4. The mean diameter of the skin test of recombinant mycobacterium tuberculosis fusion protein (EC) is not less than 5mm, or there are blisters, necrosis, lymphangiitis.

Exclusion Criteria:

1. Patients with a history of severe drug allergy, vaccine allergy, allergic constitution or known allergy to experimental drugs;
2. Patients currently suffering from tuberculosis;
3. Acute fever diseases, infectious diseases (including but not limited to measles, whooping cough, influenza, pneumonia, etc.), diabetes mellitus with complications, acute or progressive liver or kidney disease, acute conjunctivitis of the eye, acute otitis media, severe heart disease, severe hypertension, myocardial damage, significant vascular sclerosis, patients with endocarditis, patients with malignant tumors, etc.;
4. Patients with extreme weakness and severe anemia;
5. Patients with a history of convulsions, epilepsy, encephalopathy, and neurological symptoms or signs upon examination;
6. Chest imaging examination showed active tuberculosis;
7. Patients with abnormal thyroid palpation or a history of thyroid/parathyroid disease;
8. The interval between other subunit vaccines and inactivated vaccines was less than 7 days, and the interval between attenuated live vaccines was less than 14 days before enrollment;
9. Women who are pregnant or breastfeeding, who test positive for pregnancy, or who cannot guarantee contraception during the study period of this clinical trial;
10. Any circumstances which the investigator considers likely to influence the evaluation of the test.

Primary outcomes:
measure: End point of efficacy
timeFrame: through study completion, an average of 2 year
Secondary outcomes:
measure: End point of safety
timeFrame: 30 minutes and 30 days after each dose
measure: End point of safety
timeFrame: 6 months after the first dose to the full dose
measure: End point of immunogenicity
timeFrame: Treatment group: 1 month and 12 months before drug injection, after full injection; Blank control group: the day after enrollment, 1 month +10 weeks after enrollment, 12 months +10 weeks.
measure: End point of immunogenicity
timeFrame: Treatment group: 1 month and 12 months before drug injection, after full injection; Blank control group: the day after enrollment, 1 month +10 weeks after enrollment, 12 months +10 weeks.
measure: End point of immunogenicity
timeFrame: Treatment group: 1 month and 12 months before drug injection, after full injection; Blank control group: the day after enrollment, 1 month +10 weeks after enrollment, 12 months +10 weeks.
measure: End point of immunogenicity
timeFrame: Treatment group: 1 month and 12 months before drug injection, after full injection; Blank control group: the day after enrollment, 1 month +10 weeks after enrollment, 12 months +10 weeks.
Other outcomes:
Locations:
city: Liuzhou
country: China
facility: Liujiang district Prevention and Control center
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou Center for Disease Control and Prevention
state: Guangxi
Study officials:
affiliation: Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention
name: Yi Mo, Master
role: PRINCIPAL_INVESTIGATOR
References: