A Phase Ib Study of the Recombinant Mycobacterium Tuberculosis Vaccine Freeze-dried (AEC/BC02)

Tuberculosis Clinical Trial

Official title:

Phase Ib Clinical Trial Evaluating the Safety and Immunogenicity of Freeze-dried Recombinant Tuberculosis Vaccine (AEC / BC02) in Healthy Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04239313
• Other study ID #: AEC/BC02-?b-healthy
• Status: Completed
• Phase: Phase 1
• Start date: May 27, 2020
• Est. completion date: June 20, 2022

Study information

• Verified date: September 2022
• Source: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 20, 2022
• Est. primary completion date: February 24, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Biological:
• Low-dose freeze-dried recombinant tuberculosis vaccine (AEC / BC02)
Population I are coxal muscle injection of low dose vaccine.
• Low-dose adjuvant for freeze-dried recombinant tuberculosis vaccine (AEC / BC02)
Population I are coxal muscle injection of low dose adjuvant.
• Lyophilized recombinant tuberculosis vaccine (AEC / BC02) placebo
The placebo drug contains 20mg mannitol and 10 millimole(mM) phosphate buffer(PB).population I are coxal muscle injection of placebo.

Locations

Country	Name	City	State
China	Wuhan Infectious Disease Hospital	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (2)

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

Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011 Jun;12(6):509-17. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of adverse events after intramuscular 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,fourth 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 6 months 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 6 months after the sixth time injection