Phase Ⅰa Clinical Trial of a Pneumococcal Vaccine

Study Overview
=================
Brief Summary
-----------------
Infections with Streptococcus pneumoniae often cause serious health problems, especially for infants and the elderly.Failure to cover all polysaccharide types is an even greater problem with adults than with children. The aim of the study is to preliminary evaluate the safety and immunogenicity of PBPV vaccine compared to placebo,in order to provide a basis for subsequent clinical trial design.

Detailed Description
-----------------
The polysaccharide vaccine protected 60% of elderly adults who were at risk for pneumococcal infection.However, pneumococci are highly diverse with respect to their capsular types , and the polysaccharide-protein conjugate vaccines will not protect against strains of the many capsular types not included in the vaccine.This experimental vaccine was covered 70% of all pneumococcal types, Subjects will receive three doses of PBPV vaccine on day 0,60 and 120 with different contents of 20μg,50μg,100μg each antigen in 18 to 49 years of age.

Official Title
-----------------
A Phase Ⅰa Randomized,Double-Blind, Placebo-controlled Clinical Trial to Preliminary Evaluate the Safety and Immunogenicity of Protein Based Pneumococcal Vaccine（PBPV） in Healthy People Aged Between 18 and 49 Years Old

Conditions
-----------------
Pneumonia, Respiratory Tract Diseases, Respiratory Tract Infections

Intervention / Treatment
-----------------
* Biological: Protein based pneumococcal vaccine(Low dose)
* Biological: Protein based pneumococcal vaccine placebo(Low dose)
* Biological: Protein based pneumococcal vaccine(Middle dose)
* Biological: Protein based pneumococcal vaccine placebo(Middle dose)
* Biological: Protein based pneumococcal vaccine(High dose)
* Biological: Protein based pneumococcal vaccine placebo(High dose)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy volunteers aged 18 to 49 years old; Willing to provide proof of identity; Able to understand and sign the informed consent; Able and willing comply with the requirements of the protocol Exclusion Criteria: Hypertensive volunteers with uncontrollable medications (on-site measurement: systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); Abnormal changes of laboratory measures (with clinical significance); Woman is pregnant and lactating (by urine pregnancy test) Suffered from pneumonia in the past three years; Invasive diseases caused by Streptococcus pneumoniae (such as meningitis, bacteremia, pericarditis, peritonitis, etc.) in the past three years; Allergic person; Any prior administration of blood products in last 3 month; Any prior administration of other research medicines in last 1 month; Plans to participate in or is participating in any other drug clinical study; Any prior administration of attenuated live vaccine in last 14 days; Any prior administration of subunit or inactivated vaccines in last 7 days; Had fever before vaccination, volunteers with temperature >37.0℃ on axillary setting; According to the investigator's judgment, the volunteers have any otherfactors that make them unfit to participate in the clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose Group A<br>Subjects received three doses of PBPV with 20μg each antigen | Biological: Protein based pneumococcal vaccine(Low dose)<br>* 0.2mL,Intramuscular other name:PBPV<br>|
| Placebo Comparator: Low-dose Group B<br>Subjects received three doses of placebo | Biological: Protein based pneumococcal vaccine placebo(Low dose)<br>* 0.2mL,Intramuscular other name:PBPV placebo<br>|
| Experimental: Middle-dose Group A<br>Subjects received three doses of PBPV with 50μg each antigen | Biological: Protein based pneumococcal vaccine(Middle dose)<br>* 0.5mL,Intramuscular other name:PBPV<br>|
| Placebo Comparator: Middle-dose Group B<br>Subjects received three doses of placebo | Biological: Protein based pneumococcal vaccine placebo(Middle dose)<br>* 0.5mL,Intramuscular other name:PBPV placebo<br>|
| Experimental: High-dose Group A<br>Subjects received three doses of PBPV with 100μg each antigen | Biological: Protein based pneumococcal vaccine(High dose)<br>* 1.0mL,Intramuscular other name:PBPV<br>|
| Placebo Comparator: High-dose Group B<br>Subjects received three doses of placebo | Biological: Protein based pneumococcal vaccine placebo(High dose)<br>* 1.0mL,Intramuscular other name:PBPV placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety indexes of solicited and unsolicited adverse reactions | Occurrence of solicited and unsolicited reactions post each vaccination | within 30 minutes,0-7 days,0-30 days post-vaccination | 
| Safety indexes of lab measures | Occurrence of abnormal changes of hematological examination,clinical chemistry test,urine test and vital signs | day 3 and 8 post the first vaccination | 
| Safety indexes of lab measures | Occurrence of abnormal changes of CK-MB,CTN,urine test and vital signs | day 14 and 30 post each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety indexes of SAE | Occurrence of SAE | within 180 days post vaccination | 
| immunogencity indexes of GMC and GMI by ELISA | Geometric mean concentration(GMC) and Geometric mean increase（GMI）of anti-PspA-RX1 , anti-PspA-3296, anti-PspA-5668 and anti-PlyLD antibodies in serum | day 8, 14,30,60 post each vaccination | 
| immunogencity indexes of the seropositivity rates by ELISA | the seropositivity rates of anti-PspA-RX1 , anti-PspA-3296, anti-PspA-5668 and anti-PlyLD antibodies in serum | day 8, 14,30,60 post each vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccnie, PspA, Pneomolysin