Clinical trial NCT04239313: A Phase Ib Study of the Recombinant Mycobacterium Tuberculosis Vaccine Freeze-dried (AEC/BC02)
Official title: Phase Ib Clinical Trial Evaluating the Safety and Immunogenicity of Freeze-dried Recombinant Tuberculosis Vaccine (AEC / BC02) in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: Tuberculosis
Vaccine
Lead sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-01-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Single-center, single-dose, placebo-controlled, open-label trials were used to evaluate the safety and immunogenicity of low-dose adjuvants and low-dose vaccines in the upper arm deltoid muscle intramuscularly in the double negative population. Thirty (PPD-QFT-) healthy adult subjects aged 18-45 were selected and divided into placebo group, low-dose adjuvant group, and low-dose vaccine group. During the test, each subject must not change groups and inoculate drugs. Every two weeks (0-2-4-6-8-10 weeks), alternately inject a dose of placebo or left and right upper arm deltoid muscles. Low-dose adjuvant or low-dose vaccine, a total of 6 doses.

Detailed description: Single-center, single-dose, placebo-controlled, open-label trials were used to evaluate the safety and immunogenicity of low-dose adjuvants and low-dose vaccines in the upper arm deltoid muscle intramuscularly in the double negative population. Thirty (PPD-QFT-) healthy adult subjects aged 18-45 were selected and divided into placebo group, low-dose adjuvant group, and low-dose vaccine group. During the test, each subject must not change groups and inoculate drugs. Every two weeks (0-2-4-6-8-10 weeks), alternately inject a dose of placebo or left and right upper arm deltoid muscles. Low-dose adjuvant or low-dose vaccine, a total of 6 doses.

Collected adverse events within 14 days after each dose of vaccination, non-recruited adverse events within 30 days after the first dose of vaccination, subjects will receive 6 months follow-up after the last dose of vaccination, and study throughout Serious adverse events were recorded during the period. Immunogenicity will be assessed before the first dose, 24 hours after the third dose, before the fourth dose, 24 hours after the sixth dose, 1 month, and 6 months.

Eligibility criteria: Inclusion Criteria:

* (1) Age 18-45 years old, body mass index (BMI) = weight (kg) / \[(height (m) × (height (m))\], in the range of 18.0 to 29.9 (including the boundary value);
* (2) I agree to participate in this study and sign an informed consent, and I am willing and able to comply with the requirements of the clinical research protocol;
* (3) Vital signs (reference range of vital signs: systolic blood pressure 90 \~ 140mmHg (including boundary value), diastolic blood pressure 60 \~ 90mmHg (including boundary value), pulse rate 50 \~ 100 beats / min (including boundary value), body temperature (ear Temperature) 35.4 \~ 37.7 ℃ (including the boundary value)), physical examination, clinical laboratory (blood routine, urine routine, blood biochemistry, hepatitis B and AIDS syphilis examination, etc.), electrocardiogram and abdominal B-ultrasound examination, the results showed no abnormalities or abnormalities Non-clinical significance
* (4) Chest X-ray examination showed no abnormalities;
* (5) TB-PPD skin test induration average diameter \<5mm and QFT negative test results;
* (6) No contraindications to vaccination and no history of TB exposure.

Exclusion Criteria:

* (1) (Ask) Suffering from acute disease, severe chronic disease, acute episode of chronic disease, acute infectious disease, such as: treatment of malignant tumor, autoimmune disease, progressive atherosclerosis or diabetes with complications, Chronic obstructive pulmonary disease, acute or progressive liver or kidney disease, congestive heart failure, etc. that require oxygen therapy;
* (2) (Ask) those with eczema or other skin diseases;
* (3) (Ask) Those who are known to be allergic to the components of the test drug;
* (4) (Ask) those who have a clear diagnosis of tuberculosis, extrapulmonary tuberculosis or tuberculosis has been cured;
* (5) (Ask) a history of convulsions, epilepsy, encephalopathy and neurological symptoms or signs;
* (6) (Ask) long-term use of antibiotics;
* (7) (Ask) People with known or suspected immune function impairment or abnormality, such as those who received immunosuppressant or immune enhancer treatment within 3 months, received gastrointestinal within 3 months Those who have immunoglobulin preparations or blood products or plasma extracts outside the tract, those with human immunodeficiency virus infection or related diseases;
* (8) (inquiry) those who have no spleen, functional spleen, and spleen or splenectomy caused by any situation
* (9) Examination of one or more clinical significance of hepatitis B surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or anti- Treponema pallidum specific antibody;
* (10) Those who have a history of drug abuse or are positive for drug screening;
* (11) Those who donated or lost blood more than 400mL within 3 months before screening;
* (12) those with acute febrile diseases and infectious diseases;
* (13) those who are pregnant, lactating, or have a positive pregnancy test before vaccination, or who cannot guarantee contraception during the study period of this clinical trial;
* (14) Participated in other new drug clinical trials 3 months before screening;
* (15) Any situation that the investigator believes may affect the eva

Primary outcomes:
measure: The number of adverse events after intramuscular injection
timeFrame: Up to 6 months after the sixth time injection
Secondary outcomes:
measure: Laboratory markers of immunity
timeFrame: Up to 6 months after the sixth time injection
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuhan Infectious Disease Hospital
state: Hubei
Study officials:
affiliation: Wuhan infectious disease hospital
name: Zhaolin Huang
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011 Jun;12(6):509-17. doi: 10.1038/ni.2039.
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. doi: 10.1128/JCM.42.8.3594-3599.2004.