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

• ClinicalTrials.gov Identifier: NCT03813940
• Recruitment Status: Completed
• First Posted: January 23, 2019
• Last Update Posted: April 8, 2021
• Sponsor: Xiamen University
• Collaborators: Xiamen Innovax Biotech Co., Ltd; Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.
• Information provided by (Responsible Party): Jun Zhang, Xiamen University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Condylomata Acuminata; Cervical Cancer	Biological: HPV Vaccine,135μg/0.5ml; Biological: HPV Vaccine,270μg/1.0ml	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: January 3, 2019
• Actual Primary Completion Date: August 18, 2019
• Actual Study Completion Date: April 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: HPV Vaccine,135μg/0.5ml; Participants in this arm would receive 135μg/0.5ml HPV vaccines	Biological: HPV Vaccine,135μg/0.5ml; HPV vaccine (135μg/0.5ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule
Experimental: HPV Vaccine,270μg/1.0ml; Participants in this arm would receive 270μg/1.0ml HPV vaccines.	Biological: HPV Vaccine,270μg/1.0ml; HPV vaccine (270μg/1.0ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule

Outcome Measures

Primary Outcome Measures :

1. Solicited local adverse reactions [ Time Frame: During the 7-day (Day 0-6) period following each vaccination ]
   Solicited local adverse reactions occurred within 7 days after each vaccination;
2. Solicited systematic adverse reactions [ Time Frame: During the 7-day (Day 0-6) period following each vaccination ]
   Solicited systematic adverse reactions occurred within 7 days after each vaccination;
3. Unsolicited adverse events [ Time Frame: Within 30 days (Day 0-29) after any vaccination ]
   Unsolicited adverse reactions occurred within 30 days after each vaccination;
4. Serious adverse events [ Time Frame: throughout the study period, an average of 7 months ]
   Serious adverse events occurred throughout the study;

Secondary Outcome Measures :

1. Clinically Relevant Abnormalities in Blood Biochemistry [ Time Frame: Before and the second day after the first and third vaccination ]

   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".

2. Clinically Relevant Abnormalities in Hematological Parameters [ Time Frame: Before and the second day after the first and third vaccination ]

   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".

Other Outcome Measures:

1. Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 7 (type specific neutralizing antibody) [ Time Frame: month 7 ]
   To detect the anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 type specific neutralizing antibody level on day 0 (before the 1st dose) and one month after dose 3
2. Anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion rates and geometric mean concentrations at Months 7 (type specific IgG antibody) [ Time Frame: month 7 ]
   To detect the anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 type specific IgG antibody level on day 0 (before the 1st dose) and one month after dose 3

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Health people aged between 18 and 45 years.
2. Judged as healthy and eligible for vaccination by the investigators through a self-reported medical history and some physical examinations.
3. Able to comply with the requests of the study.
4. Written informed consent obtained from the participants.
5. Axillary temperature not higher than 37.0°C
6. Men, or non-pregnant women verified by a urine pregnancy test.

Exclusion criteria:

1. Pregnant or breastfeeding or plan to be pregnant within 7 months.
2. 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.
3. Received immunosuppressed, immunoregulation therapy or corticosteroid systemic therapy for more than 14 days in the 6 months before entry, except local treatment.
4. 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.
5. 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.
6. 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.
7. Having the plan to participate another clinical trial during the study period.
8. Received another HPV vaccine.
9. 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).
10. History of allergic disease or history of serious adverse events occurring after vaccination, i.e., allergy, urticaria, dyspnea, angioneurotic edema or abdominal pain.
11. Asthma that required emergent treatment, hospitalization, oral or intravenous corticosteroid for unstable condition within the past 2 years.
12. Having serious disease of internal medicine, such as hypertension(systolic blood pressure > 140mmHg or diastolic blood pressure >90mmHg), cardiac disease, diabetes, hyperthyroidism et al.
13. 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.

Contacts and Locations

Locations

China, Jiangsu

Jiangsu Provincial Centre for Disease Control and Prevention

Nanjing, Jiangsu, China, 210009

Sponsors and Collaborators

Xiamen University

Xiamen Innovax Biotech Co., Ltd

Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.

Investigators

• Study Chair: Jun Zhang, Master; Xiamen University
• Principal Investigator: Yue-Mei Hu, Bachelor; Jiangsu Provincial Centre for Disease Control and Prevention

More Information

• Responsible Party: Jun Zhang, Professor, Xiamen University
• ClinicalTrials.gov Identifier: NCT03813940
• Other Study ID Numbers: HPV-PRO-007
• First Posted: January 23, 2019
• Last Update Posted: April 8, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jun Zhang, Xiamen University:

human papillomavirus vaccine

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs