Human Papillomavirus Infection
Conditions
Keywords
CIN, VIN, VaIN, AIN, Cervical cancer, Vaginal cancer, vulvar cancer, Anal cancer, Genital warts
Brief summary
This study is to evaluate the safety and tolerability profile of Recombinant Nonavalent (Types 6/11/16/18/31/33/45/52/58) Human Papillomavirus (HPV) Vaccine (Escherichia Coli) in healthy women ages 18-45
Detailed description
This is a single-centre, dose-escalating, randomized, blinded and active controlled trial in healthy Chinese women ages 18-45. The positive control is Recombinant nonavalent Human Papillomavirus (Types 6,11,16,18,31,33,45,52,58) Vaccine. The trial will be conducted in two stages: Stage 1: A single-center, open-label trial will be carried out in 40 healthy women ages 27-45 in the enrolment order of mid-dosage group followed by high-dosage group. Each group of 20 subjects will be administered the mid-, and high-dosage form, respectively, to preliminarily evaluate the safety profile of the investigational vaccine. First, the 20 subjects in the mid-dosage group will be sequentially enrolled as two batches of 5 and 15 subjects, respectively, at an enrolment interval of no less than 3 days. One week after vaccinating all the 20 subjects in the mid-dosage group, upon confirmation of the safety profile of the investigational vaccine as acceptable, 20 subjects for the higher dosage-group will be enrolled subsequently in the same manner as those in the mid-dosage group. Subjects in each dosage group will receive a 3-dose regimen at months 0, 2 and 6. Safety of the investigational vaccine will be assessed for 30 days following each injection, and SAE will be reported for the duration of the study. In total there will be 12 scheduled visits for subjects in each dosage group throughout the study. One week after vaccinating all the 40 subjects in stage 1, if the safety profile of the investigational vaccine is confirmed to be acceptable, the study may proceed to stage 2. Stage 2: A phase I, single-center, dose-escalating, randomized and blinded (as to intra-dosage group) trial, with Gardasil9 as the positive control will be carried out in 120 healthy women ages 18-26 in the enrolment order of low-, mid-, and high-dosage groups. Each group of 40 subjects will be enrolled and randomized at a 3: 1 ratio to receive the investigational vaccine or positive control, respectively (that is, 10 of the subjects in each dosage group will receive the positive control). Firstly, the 40 subjects in the low-dosage group will be sequentially enrolled as four batches of 5, 10, 10 and 15 subjects, respectively, at an enrolment interval of no less than 3 days to get the first dose of the low-dosage investigational vaccine or positive control. Then, one week after vaccinating all the 40 subjects in the low-dosage group, upon confirmation of the safety profile of the investigational vaccine as acceptable, 40 subjects will be enrolled subsequently into the mid-dosage group in the same manner as those in the low-dosage group. Again, one week after vaccinating the 40 subjects in the mid-dosage group, if the safety profile of the investigational vaccine continues to be acceptable, another group of 40 subjects receiving the high-dosage investigational vaccine or positive control will be enrolled subsequently in the same manner as those in the low-dosage group. In both stage 1 and stage 2 of the phase I study, 5 ml of non-anticoagulative blood will be collected from trial subjects prior to dose 1 and at Month 3 and Month 7 post dose 1 to determine the levels of neutralizing antibodies and IgG antibodies to the vaccine HPV types.
Interventions
For Low-dosage group, a 3-dose regimen administered at months 0, 2 and 6. For Mid-dosage group, a 3-dose regimen administered at months 0, 2 and 6. For High-dosage group, a 3-dose regimen administered at months 0, 2 and 6.
BIOLOGICALRecombinant nonavalent Human Papillomavirus (Types 6,11,16,18,31,33,45,52,58) Vaccine
A 3-dose regimen administered at months 0, 2 and 6.
Sponsors
Jiangsu Province Centers for Disease Control and Prevention
National Institutes for Food and Drug Control, China
Nanjing Sangruisi Pharmaceutical Technology Co., Ltd
School of Public Health of Southeastern University
Beijing Health Guard Biotechnology, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
The Sponsor, investigators and biostatisticians will remain blinded to subject allocation.
Intervention model description
The trial will be conducted in two stages: Stage 1: An open-label trial will be carried out in 40 healthy women ages 27-45 in the enrolment order of mid-dosage group followed by high-dosage group. Each group of 20 subjects will be administered the mid-, and high-dosage form respectively. Stage 2: A randomized and blinded (as to intra-dosage group) trial, with Gardasil9 as the positive control will be carried out in 120 healthy women ages 18-26 in the enrolment order of low-, mid-, and high-dosage groups. Each group of 40 subjects will be enrolled and randomized at a 3: 1 ratio to receive the investigational vaccine or positive control, respectively.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Stage 1: 1. Female subjects 27-45 years of age (inclusive of 27 and 45 years of age); 2. Subjects decided to be healthy by the principal investigator in accordance with such trial subjects' medical history and physical examination results; 3. Subjects who understand and agree to comply with the study procedures and provide written informed consent; 4. Subjects who are able to comply with protocol-specified requirements; 5. Subjects with negative urine pregnancy test result at screening; 6. Subjects with no childbearing potential (e.g. females who have undergone bilateral tubal ligation, hysterectomy, bilateral oophorectomy, etc.), or subjects with childbearing potential who have agreed to abstain from any sexual activity that could result in pregnancy or practice adequate contraception for at least 28 days prior to the first dose and throughout the study; 7. Subjects with axillary temperature≤37.0℃. Stage 2: 1. Female subjects 18-26 years of age (inclusive of 18 and 26 years of age); 2. Subjects decided to be healthy by the principal investigator in accordance with such trial subjects' medical history and physical examination results; 3. Subjects who understand and agree to comply with the study procedures and provide written informed consent; 4. Subjects who are able to comply with protocol-specified requirements; 5. Subjects with negative urine pregnancy test result at screening; 6. Subjects with no childbearing potential (e.g. females who have undergone bilateral tubal ligation, hysterectomy, bilateral oophorectomy, etc), or subjects with childbearing potential who have agreed to abstain from any sexual activity that could result in pregnancy or practice adequate contraception for at least 28 days prior to the first dose and throughout the study; 7. Subjects with axillary temperature≤37.0℃.
Exclusion criteria
The same
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of adverse reaction(s) within 7 days post any dose of the interventions. | 0-7 months | Percentage of subjects with 1 or more injection-site or non-injection-site (systemic) adverse reaction(s) within 7 days post any dose of the interventions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of abnormal blood routine indexes, coagulation time and blood biochemical indexes | The 3rd and 7th month after immunization | Percentage of subjects with abnormal blood routine indexes (concentrations of hemoglobin, white blood cells count), abnormal coagulation time (PT, APTT), and abnormal blood biochemical indexes (creatinine, alanine aminotransferase, aspartate aminotransferase) 3 days after any any dose of the interventions. |
| Percentage of serious adverse event(s) | 0-7 months | Percentage of subjects with serious adverse event(s) for the duration of the study (about 7 months). |
| Levels of neutralization antibodies against each vaccine HPV type (6/11/16/18/31/33/45/52/58) | The 7th month after immunization | Levels of neutralization antibodies against each vaccine HPV type (6/11/16/18/31/33/45/52/58) one month post dose 3 (Month 7) among trial subjects. |
| Percentage of subjects positive for neutralization antibodies against each vaccine HPV type (6/11/16/18/31/33/45/52/58) | The 7th month after immunization | Percentage of subjects positive for neutralization antibodies against each vaccine HPV type (6/11/16/18/31/33/45/52/58) one month post dose 3 (Month 7) among trial subjects. |
| Levels of IgG antibodies | The 7th month after immunization | Levels of IgG antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) one month post dose 3 (Month 7) among trial subjects. |
| Seropositive rates of IgG antibodies | The 7th month after immunization | Seropositive rates of IgG antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) one month post dose 3 (Month 7) among trial subjects. |
| Percentage of adverse event(s) within 30 days post any dose of the interventions | The 3rd day after each injection | Percentage of subjects with 1 or more injection-site or non-injection-site (systemic) adverse event(s) within 30 days post any dose of the interventions |
| Seropositive rates of neutralizing antibodies | The 3rd month after immunization | Seropositive rates of neutralizing antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) at month 3 post dose 1 among trial subjects. |
| Seroconversion rates of neutralizing antibodies | The 3rd and 7th month after immunization | Seroconversion rates of neutralizing antibodies Seroconversion rates of neutralizing antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) at Month 3 and Month 7 post dose 1, respectively, among trial subjects. |
| Seroconversion rates of IgG antibodies | The 3rd and 7th month after immunization | Seroconversion rates of IgG antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) at Month 3 and Month 7 post dose 1, respectively, among trial subjects. |
| Fold increases in levels of neutralizing antibodies and IgG antibodies | The 3rd and 7th month after immunization | Fold increases in levels of neutralizing antibodies and IgG antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) at Month 3 and Month 7 post dose 1, respectively, among trial subjects. |
| Fold increases in neutralizing antibodies | Before immunization, and the 3rd and 7th month after immunization | Fold increases in neutralizing antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) at Month 3 and Month 7 post dose 1, respectively, among trial subjects who were negative for antibodies to the corresponding HPV type (HPV 6/11/16/18/31/33/45/52/58) prior to dose 1 |
| Fold increases in IgG antibodies | Before immunization, and the 3rd and 7th month after immunization | Fold increases in IgG antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) at Month 3 and Month 7 post dose 1, respectively, among trial subjects who were negative for antibodies to the corresponding HPV type (HPV 6/11/16/18/31/33/45/52/58) prior to dose 1 |
| Levels of neutralizing antibodies | The 3rd month after immunization | Levels of neutralizing antibodies to each vaccine HPV type (6/11/16/18/31/33/45/52/58) at month 3 post dose 1 among trial subjects. |
Countries
China
Outcome results
None listed