Safety Evaluation of Meningococcal Group ACYW135 Conjugate Vaccine in 2-month to 55 Years Old Population.

Study Overview
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Brief Summary
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A single-center and open-labeled Phase I study, designed to evaluate the safety by observing the occurrence of adverse events and change of hematology, liver and renal function after vaccination of a meningococcal group A, C, Y, and W135 conjugate vaccine in healthy population aged 2 months to 55 years old.

Official Title
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Phase I Clinical Study of Meningococcal Group ACYW135 Conjugate Vaccine

Conditions
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Meningococcal Infections

Intervention / Treatment
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* Biological: Meningococcal Group ACYW135 Conjugate Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children, adolescents and adults (age range: 2 months to 55 years old) based on medical history, physical examination or judgement of the investigator Subjects aged ≥18 years old voluntarily agree to participate in this clinical study and sign the informed consent form; or for subjects aged <18 years old, the legal guardian voluntarily agrees that his/her child to participate in this clinical study, and sign the informed consent form. For juveniles aged ≥8 years old, both the subject and his/her legal guardians should voluntarily agree to participate in this clinical study and sign the informed consent form. The subject and his/her legal guardians as well as the family members are able to follow the request of clinical study protocol. Subjects aged 2 or 3 months should have no vaccination history of any meningococcal vaccine; subjects aged 7 23 months should have not received any other meningococcal vaccine except the meningococcal group A polysaccharide vaccine included in National Immunization Program, and the time since last vaccination of meningococcal group A polysaccharide vaccine should be >6 months; for subjects ≥2 years, the time since last vaccination of meningococcal vaccine should be >2 years. For subjects aged ≥2 years, there should be no clinically significant abnormal hematology, liver and renal function results judged by the investigator before immunization. Subjects should not receive any attenuated live vaccine 14 days, or inactivated vaccine 7 days before or after vaccination. Axillary temperature ≤37.0℃. Exclusion Criteria for First Dose: Subjects aged 2 or 3 months at enrollment with birth weight <2.5 kg. Subjects aged 2 or 3 months at enrollment had received blood products and immunoglobin after birth; subjects of other age groups had received blood products or immunoglobin in <3 months before vaccination. Subjects aged <12 months at enrollment are diagnosed as with pathological jaundice or have a history of pathological jaundice. Subjects aged <2 months at enrollment had abnormal labor (dystocia, assisted instrumental delivery) or with the history of asphyxia or nervous damage. Subjects aged ≥18 years who are planning pregnancy, or are pregnant, or are breastfeeding. Subjects aged ≥18 years with uncontrollable hypertension (during screening: systolic BP >140 mmHg or diastolic BP >90 mmHg). Subjects are known to be allergic to certain components contained in the investigational vaccine (mainly include: capsular polysaccharide of meningococcal group A, group C, group Y, or group W135, diphtheria toxoid or diphtheria antigen). Subjects with the history of serious allergy to any vaccine or drug. (including but not limited to: allergic shock, allergic laryngeal edema, allergic purpura, thrombocytopenic purpura, local allergic necrosis reaction [Arthus reaction]). Subjects with the history of meningitis. Subjects with moderate to severe fever (axillary temperature ≥38.0℃) in last 3 days. Subjects with the history or family history of convulsion, seizure, encephalopathy, or psychiatric disorders. Subjects with definite diagnosis of thrombocytopenia or other coagulation disorders. Subjects with primary or secondary immunological dysfunction, including HIV infection, disorder or resection of thyroid, pancreas, liver, spleen or kidney; or needed treatment due to thyroid disorders in last 12 months (time interval <12 months). Subjects have received immunosuppressive therapy, cytotoxic therapy, corticosteroid hormone (not include corticosteroid hormone spray for allergic rhinitis, epithelial corticosteroid hormone for acute and non-complicated dermatitis) in last 6 months (time interval <6 months). Subjects with known congenital malformation, developmental disabilities or clinically confirmed serious chronic diseases (e.g., Down syndrome, diabetes mellitus, sickle cell anemia or nervous disease, Guillain-Barre syndrome, etc.). Subjects with known or suspected diseases that are likely to affect the vaccination by investigators' judgement, such as: serious respiratory diseases, acute infection or the active period of chronic disease, serious cardiovascular diseases, liver and renal diseases, malignant tumors, serious infectious or allergic skin diseases. Subjects are participating or plan to participate in other clinical trials of investigational medications. Any other conditions that may influence the evaluation of clinical study by investigators' judgement. Exclusion Criteria for Second and Third Dose: New conditions that conforms with the exclusion criteria for first dose. Subjects that develop grade 4 adverse reactions after vaccination of investigational vaccine. Subjects that develop serious allergic reactions after vaccination of investigational vaccine. Any other conditions that may influence the evaluation of clinical study by investigators' judgement based on the exclusion criteria for first dose.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18 55 yrs<br>1 dose of meningococcal group ACYW135 conjugate vaccine will be administered on day 0. | Biological: Meningococcal Group ACYW135 Conjugate Vaccine<br>* 1 dose in Stage 1 (2 55 yrs), 2 doses in Stage 2 (7 23 mos), and 3 doses in Stage 3 (2&3 mos)<br>|
| Experimental: 2 17 yrs<br>1 dose of meningococcal group ACYW135 conjugate vaccine will be administered on day 0. | Biological: Meningococcal Group ACYW135 Conjugate Vaccine<br>* 1 dose in Stage 1 (2 55 yrs), 2 doses in Stage 2 (7 23 mos), and 3 doses in Stage 3 (2&3 mos)<br>|
| Experimental: 7 23 mos<br>2 doses of meningococcal group ACYW135 conjugate vaccine will be administered. One-month interval between the first and second dose. | Biological: Meningococcal Group ACYW135 Conjugate Vaccine<br>* 1 dose in Stage 1 (2 55 yrs), 2 doses in Stage 2 (7 23 mos), and 3 doses in Stage 3 (2&3 mos)<br>|
| Experimental: 3 mos<br>3 doses of meningococcal group ACYW135 conjugate vaccine will be administered. One-month interval between every two doses. | Biological: Meningococcal Group ACYW135 Conjugate Vaccine<br>* 1 dose in Stage 1 (2 55 yrs), 2 doses in Stage 2 (7 23 mos), and 3 doses in Stage 3 (2&3 mos)<br>|
| Experimental: 2 mos<br>3 doses of meningococcal group ACYW135 conjugate vaccine will be administered. Two-month interval between every two doses. | Biological: Meningococcal Group ACYW135 Conjugate Vaccine<br>* 1 dose in Stage 1 (2 55 yrs), 2 doses in Stage 2 (7 23 mos), and 3 doses in Stage 3 (2&3 mos)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events after each vaccination | Percentage of subjects with local and systemic adverse events after each dose of vaccination | 30 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious adverse events after vaccination | Percentage of subjects with serious adverse events from day 0 to 6 months after last dose | day 0 to 6 months after last dose | 
| Blood routine in 2 years and above subjects | content of hemoglobin（g/dL）、white blood cell count（WBC）、blood platelet count（PLT）3 days after vaccination in 2 years and above subjects | 3 days after vaccination | 
| Liver function in 2 years and above subjects | Alanine aminotransferase（ALT），Aspartate aminotransferase（AST），Total bilirubin(TBIL) 3 days after vaccination in 2 years and above subjects | 3 days after vaccination | 
| Renal function in 2 years and above subjects | Creatinine（CR），Urea nitrogen（BUN）3 days after vaccination in 2 years and above subjects | 3 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningitis, Meningococcal, Serogroup A, Meningitis, Meningococcal, Serogroup C, Meningitis, Meningococcal, Serogroup Y, Meningitis, Meningococcal, Serogroup W135