Safety Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli)

Study Overview
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Brief Summary
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This phase I clinical study was designed to evaluate the safety of Recombinant Human Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type)(E.Coli)(hereafter called HPV vaccine), manufactured by Xiamen Innovax Biotech CO., LTD., in healthy adults aged 18-45 years old.

Detailed Description
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The study would have 2 stages. In the first stage, around 12 healthy adults aged 18-45 (male vs female,around 1:1)would receive 135μg/0.5ml of the HPV vaccine, the participants would be actively followed up for 7 days, if no vaccine related serious adverse events(SAE) occurred and the vaccine is well tolerated, another group of 12 healthy adults aged 18-45 (male vs female,around 1:1)would be enrolled and would receive 270μg/0.5ml of the HPV vaccine. The vaccine would be administered intramuscularly at day 0, month 1 and month 6. All the participants would be actively monitored for adverse reactions/events for 1 month after each injection. SAE during the trial were followed up. And blood, liver and kidney function changes will be monitored before and 2 days after the first and third vaccination. Serum samples from all the subjects would be collected on day 0 and month 7 to test immunogenicity as exploratory analysis.

Official Title
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An Open-Label, Single-Center Phase I Clinical Trial to Estimate Safety of the Recombinant Human Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type) (E.Coli) in Healthy Adults Aged 18 to 45 Years

Conditions
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Condylomata Acuminata, Cervical Cancer

Intervention / Treatment
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* Biological: HPV Vaccine,135μg/0.5ml
* Biological: HPV Vaccine,270μg/1.0ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Health people aged between 18 and 45 years. Judged as healthy and eligible for vaccination by the investigators through a self-reported medical history and some physical examinations. Able to comply with the requests of the study. Written informed consent obtained from the participants. Axillary temperature not higher than 37.0°C Men, or non-pregnant women verified by a urine pregnancy test. Exclusion criteria: Pregnant or breastfeeding or plan to be pregnant within 7 months. Use of any investigational product or non-registered product (drug or vaccine) within 30 days preceding the first dose of the study vaccine or plan to use during the study period. Received immunosuppressed, immunoregulation therapy or corticosteroid systemic therapy for more than 14 days in the 6 months before entry, except local treatment. Administration of any immunoglobulin or blood products within 3 months preceding the first dose of the study vaccine or plan to use within 7 months. Administration of any attenuated live vaccines within 21 days preceding the first dose of the study vaccine or any subunit or inactivated vaccines within 14 days before vaccination. Had a fever (axillary temperature over 38°C) within 3 days or acute illness requiring systemic antibiotics or antiviral treatment within 5 days before vaccination. Having the plan to participate another clinical trial during the study period. Received another HPV vaccine. Immunodeficiency , primary disease of important organs, malignant tumor, or any immune disease (such as systemic lupus erythematosus, arthritis pauperum, splenectomy or functional asplenia or other disease which might affect immune response). History of allergic disease or history of serious adverse events occurring after vaccination, i.e., allergy, urticaria, dyspnea, angioneurotic edema or abdominal pain. Asthma that required emergent treatment, hospitalization, oral or intravenous corticosteroid for unstable condition within the past 2 years. Having serious disease of internal medicine, such as hypertension(systolic blood pressure > 140mmHg or diastolic blood pressure >90mmHg), cardiac disease, diabetes, hyperthyroidism et al. Diagnosed coagulant function abnormality or blood coagulation disorder. 14) The results of blood routine test and blood biochemical test were abnormal. The grade was 2 or above. 15) Epilepsy, except fever epilepsy at under 2 years of age, alcohol-induced epilepsy in 3 years before abstinence, or idiopathic epilepsy requiring no treatment in the past 3 years. 16) Past or current two-stage affective psychosis, not well controlled in the past 2 years or requiring drugs, or hve a tendency to commit suicide in the past 5 years. 17) Other medical, psychological, social or occupational factors that, according to the investigators' judgment, might affect the individual's ability to obey the protocol or sign the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPV Vaccine,135μg/0.5ml<br>Participants in this arm would receive 135μg/0.5ml HPV vaccines | Biological: HPV Vaccine,135μg/0.5ml<br>* HPV vaccine (135μg/0.5ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule<br>|
| Experimental: HPV Vaccine,270μg/1.0ml<br>Participants in this arm would receive 270μg/1.0ml HPV vaccines. | Biological: HPV Vaccine,270μg/1.0ml<br>* HPV vaccine (270μg/1.0ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited local adverse reactions | Solicited local adverse reactions occurred within 7 days after each vaccination; | During the 7-day (Day 0-6) period following each vaccination | 
| Solicited systematic adverse reactions | Solicited systematic adverse reactions occurred within 7 days after each vaccination; | During the 7-day (Day 0-6) period following each vaccination | 
| Unsolicited adverse events | Unsolicited adverse reactions occurred within 30 days after each vaccination; | Within 30 days (Day 0-29) after any vaccination | 
| Serious adverse events | Serious adverse events occurred throughout the study; | throughout the study period, an average of 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Relevant Abnormalities in Blood Biochemistry | Biochemical parameters assessed in blood samples include alanine aminotransferase (ALT), aspartate aminotransferase basophils, total bilirubin, direct bilirubin, indirect bilirubin, creatinine, urea nitrogen. Abnormalities reported include values outside the normal ranges: values higher than normal are designated as Above and values lower than normal as Below. | Before and the second day after the first and third vaccination | 
| Clinically Relevant Abnormalities in Hematological Parameters | Hematological Parameters assessed in blood samples include platelets, red blood cell, hemoglobin and white blood cells. Abnormalities reported include values outside the normal ranges: values higher than normal are designated as Above and values lower than normal as Below. | Before and the second day after the first and third vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human papillomavirus vaccine