Phase II/III of Live Attenuated Mumps (F-genotype) Vaccine (Human Diploid Cell, KMB-17) in Healthy Children Aged 5-11

Study Overview
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Brief Summary
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Mumps is an acute infectious respiratory disease caused by the mumps virus (MuV), which occurs mainly in children and adolescents. Its main clinical symptoms were parotid gland suppurative swelling and pain with fever. The pathological changes and harm caused by mumps was not only confined to the parotid gland, on the contrary, the social harm caused by serious complications cannot be ignored. As mumps is a vaccine-preventable infectious disease, vaccination is a fundamental strategy for controlling mumps. So far, there are 13 genotypes of MuV. Based on the analysis of molecular epidemiology, the main epidemic strain of MuV in China was the F genotype. The commonly used vaccine strains represented only a small number of known genotypes, e.g. Jeryl-Lynn (JL) and Rubini strains, which belong to type A, Urabe strain belongs to type B, and L-Zagreb strains belongs to type D. Virus seed of Live Attenuated Mumps Vaccine (Human diploid cell) developed by the institute was SP-A strain, which was the first separation and preparation of the attenuated mumps viruses in China. SP-A belongs to F genotype, which was the domestic epidemic genotype. In addition, the cell substrate prepared for vaccine was human diploid cell (KMB-17 strain), which is much safer to use. The results of phase I and II clinical trials showed that the vaccine possessed good immunogenicity and good antigenic cross-reactivity in infants (8-24 months old).

Detailed Description
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This study will recruit 12,000 subjects and be divided into two stages. The first stage will evaluate the immunogenicity and safety of F-genotype mumps live attenuated vaccine (human diploid cells) after vaccination in 720 healthy children aged 5-11 years, and explore the detoxification in 144 subjects, who randomly selected from these 720 subjects. The second stage will evaluate the clinical protective efficacy, immunogenicity and safety of F-genotype mumps live attenuated vaccine (human diploid cells) after vaccination in 11280 healthy children aged 5-11 years.

Official Title
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Phase II/III of Live Attenuated Mumps (F-genotype) Vaccine (Human Diploid Cell, KMB-17) in Healthy Children Aged 5-11

Conditions
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Epidemic Parotitis, Mumps

Intervention / Treatment
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* Biological: Attenuated Mumps vaccine (KMB-17) in phase II and III
* Biological: Placebo in phase II
* Biological: Attenuated Mumps vaccine (KMB-17) in phase III
* Biological: Placebo in phase III


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy people aged 5-11 years (including boundary values), both men and women. Proven legal identity. Participants and parent(s)/legal guardian(s) should understand the contents of the informed consent form, the vaccine in this trial, voluntarily sign the informed consent form, and be capable of using thermometers, scales, and filling in diary cards and contact cards as required. Participants and parent(s)/legal guardian(s) should be able to communicate well with investigators, understand and comply with the requirements of this trial. Axillary temperature ≤37.0 ℃. Exclusion Criteria: Contraindications for vaccination. History of allergy to vaccines or drugs Have a history of mumps disease Except for one dose of vaccine containing mumps at the age of 18 24 months before enrollment, any vaccine containing mumps has been vaccinated. Any prior administration of attenuated live vaccine in last 15 days;Any prior administration of subunit or inactivated vaccines in last 7 days Convulsant,encephalopathy,psychosis or family history of epileptics. Those who developed acute disease within 2 weeks, or had symptoms of fever or upper respiratory tract infection within 7 days. For any reason, the spleen was removed partially or completely Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder,it will cause the contraindication of subcutaneous injection Suffering from congenital deformity or serious chronic disease(congenital heart disease，Down's syndrome,diabetes,sickle cell anemia,nervous illness,angiocardiopathy,hypertension,bronchitis,pneumonia,asthma,infectious skin diseases) Any prior administration of blood products(immunoglobulin etc.) in last 1 month;Any prior administration of immunodepressant, cytotoxic drugs or corticosteroids in last 6 months(except the corticosteroids spray can treat irritability rhinitis or corticosteroids to cure noncomplication acute dermatitis ). Receipt of immunosuppressive therapy within 6 months before signing the informed consent form, such as long-term systemic glucocorticoid therapy (with systemic glucocorticoid therapy for more than 2 weeks within 6 months, such as prednisone or similar drugs) ), but local administration (such as ointment, eye drops, inhalation, or nasal spray) is allowed. The local administration should not exceed the dosage recommended in the instructions or have any signs of systemic exposure. Any prior administration of other research medicines during the same period. Any other situations judged by investigators as not suitable for participating in this study

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 11 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: Parallel Assignment
Interventional Model Description: A randomized, double-blind, placebo-controlled design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Attenuated Mumps vaccine (KMB-17) in phase II and III<br>≥4.3logCCID50/ml Attenuated Mumps vaccine (KMB-17)[≥4.3 logCCID50/ml] in 360 children (5-11 years old) on 0 day | Biological: Attenuated Mumps vaccine (KMB-17) in phase II and III<br>* ≥4.3logCCID50/ml Attenuated Mumps vaccine (KMB-17)[≥4.3 logCCID50/ml] in 360 children (5-11 years old) on 0 day<br>|
| Placebo Comparator: Placebo in phase II<br>Freeze-dried stabilizer and diluent without mumps virus antigen in 360 children (5-11 years old) on 0 day | Biological: Placebo in phase II<br>* Freeze-dried stabilizer and diluent without mumps virus antigen in 360 children (5-11 years old) on 0 day<br>|
| Experimental: Attenuated Mumps vaccine (KMB-17) in phase III<br>≥4.3logCCID50/ml Attenuated Mumps vaccine (KMB-17)[≥4.3 logCCID50/ml] in 5640 children (5-11 years old) on 0 day | Biological: Attenuated Mumps vaccine (KMB-17) in phase III<br>* ≥4.3logCCID50/ml Attenuated Mumps vaccine (KMB-17)[≥4.3 logCCID50/ml] in 5640 children (5-11 years old) on 0 day<br>|
| Placebo Comparator: Placebo in phase III<br>Freeze-dried stabilizer and diluent without mumps virus antigen in 5640 children (5-11 years old) on 0 day | Biological: Placebo in phase III<br>* Freeze-dried stabilizer and diluent without mumps virus antigen in 5640 children (5-11 years old) on 0 day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: Positive conversion rate of MuV hemagglutination inhibition antibody of Muv Vaccine | To compared the positive conversion rate of MuV hemagglutination inhibition antibody at 28 days after vaccination. | 28 day after the vaccination | 
| Phase II: Positive conversion rate of MuV neutralization antibody of MuV Vaccine | To compared the positive conversion rate of Muv hemagglutination inhibition antibody at 28 days after vaccination. | 28 day after the vaccination | 
| Phase III: The protective effect of the MuV vaccine group compared with the placebo group in preventing mumps according with the protocol | To compared the the number of cases of mumps in the vaccine group and the placebo group after 29-day-post injection within 12 months after vaccination | within 12 months after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II/III: Adverse reactions/events rate | Occurence of adverse reactions/events within 0-14 days after vaccination | within 14 days after vaccination | 
| Phase II/III: Adverse reactions/events rate | Occurence of adverse reactions/events within 0-28 days after vaccination | within 28 days after vaccination | 
| Phase II/III: Serious adverse events rate | Occurence of serious adverse events within 12 months after vaccination | within 12 months after vaccination | 
| Phase II/III: Positive rate of the hemagglutination inhibition antibody and neutralizing antibody | To compared positive rate of the hemagglutination inhibition antibody and neutralizing antibodies against MuV at 28 days after the vaccination | 28 day after the vaccination | 
| Phase II/III: The GMT of the hemagglutination inhibition antibody and neutralizing antibody | To compared the GMT of the hemagglutination inhibition antibody and neutralizing antibodies against MuV at 28 days after the vaccination | 28 day after the vaccination | 
| Phase III: The protective effect of the MuV vaccine group compared with the placebo group in preventing mumps | To compared the the number of cases of mumps in the vaccine group and the placebo group after injection within 12 months after vaccination | within 12 months after vaccination | 
| Phase III: Positive conversion rate of MuV hemagglutination inhibition antibody of Muv Vaccine | To compared the positive conversion rate of MuV hemagglutination inhibition antibody at 28 days after vaccination. | 28 day after the vaccination | 
| Phase III: Positive conversion rate of MuV neutralization antibody of MuV Vaccine | To compared the positive conversion rate of Muv hemagglutination inhibition antibody at 28 days after vaccination. | 28 day after the vaccination | 
| Phase II/III: Positive rate of the hemagglutination inhibition antibody and neutralizing antibody | To compared positive rate of the hemagglutination inhibition antibody and neutralizing antibodies against MuV at 12 months after the vaccination | 12 months after vaccination | 
| Phase II/III: The GMT of the hemagglutination inhibition antibody and neutralizing antibody | To compared the GMT of the hemagglutination inhibition antibody and neutralizing antibodies against MuV at 12 months after the vaccination | 12 months after vaccination | 
| Phase II/III: Detoxification | Viral copies in pharyngeal swabs or gargles at 3, 7, 14, 28 days after vaccination were tested by PCR. | at 3, 7, 14, 28 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mumps, F-genotype, Live Attenuated Vaccine, Human Diploid Cell