Trial of HPV Vaccine in Healthy Adult and Adolescent Female

Human Papilloma Virus Vaccine Clinical Trial

— HPV  

Official title:

Randomized, Double-Blinded, Active Controlled, Phase I/ II Clinical Trial to Assess the Immunogenicity, Safety, and Tolerability of NBP615 Vaccine in Healthy Female Participants Aged 19 to 26 Years and Adolescent Aged 9 to 13 Years

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03855150
• Other study ID #: PR-18062
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 22, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: February 2019
• Source: International Centre for Diarrhoeal Disease Research, Bangladesh
• Contact: Khalequz Zaman, PhD
• Phone: +880-1713047100
• Email: kzaman[@]icddrb.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, active-controlled, phaseI/II clinical trial to enroll 200 healthy female including 80 healthy adult aged 19 to 26 years and 120 adolescents aged 9 to 13 years to assess the safety and immunogenicity of NBP615 in comparison with Gardasil.

In order to confirm the safety, 80 healthy adult should be enrolled first, and the safety of the test product (NBP615) will be confirmed by 2nd vaccination in adults. After that, enrolled of 120 adolescents proceeds. participants who previously agreed to participate in the study will be screened and only those participants who met the inclusion/exclusion criteria will be randomized in to 1:1 to receive test product (NBP615) or reference product (Gardasil pre-filled syringe). Three/ Two doses of 0.5 ml IM injection will be given and two blood sample, pre vaccine and post vaccine 4 weeks after completion of vaccine will be collected to assess the immunogenicity of NBP615 and Gardasil, comparator HPV vaccine. Solicited adverse events occurring up to 7 days after each dose of the investigational product will be collected in the diary card. Unsolicited adverse events occurring up to 28 days after each dose of the investigational product will be collated in the diary card. Serious adverse events will be collected during the entire study period. In addition to this safety data will be collected through the study period by active contact with the study participants by doing home visit or by telephone contact.

Description:

Background (brief):

Burden: HPV is one of the most common organism causing sexually transmitted diseases (STDs). 70% of the infections disappear within one year, and 90% disappear within two years. However, if the infection continues, 5-10% of the infected women are at risk for developing precancerous lesions in the cervix, which can lead to invasive cervical cancer. About 500,000 cases are reported annually, which makes it the second most common cancer occurring among women in the world. In developed countries, mortality and incidence rates have declined by about 70% because an early detection system. However, in the countries where screening tests are not commonly provided, incidence rates remain high. Approximately 80% of all reported cases are diagnosed in the developing and least developed countries, and the number of deaths due to cervical cancer has reached 230,000 cases. Almost all cases of cervical cancer are caused by HPV infection. Prevalence of human papillomavirus (HPV) infection among the general populations in South Asian countries like India, Bangladesh, Nepal and Sri Lanka varies from 7-14% and the age-specific prevalence across age groups is constant with no clear peak in young women. Current estimates indicate that every year 11956 women are diagnosed with cervical cancer and 6582 die from the disease. Cervical cancer ranks as the 2nd most frequent cancer among women in Bangladesh and the 2nd most frequent cancer among women between 15 and 44 years of age. A prospective cohort study that was conducted in one urban and one rural area of Bangladesh showed that prevalence of any HPV infection was 7.7% with no significant difference between urban and rural women. Most common high-risk genotypes were HPV16, HPV66, HPV18, HPV45, HPV31 and HPV53.

Cervical cancer can be diagnosed and treated in advance, due to its long development period. However, costs for treating the cancer are high, and since underdeveloped countries do not have an effective early detection system, the incidence rate is higher for the underdeveloped countries. Preventing infection through vaccination is therefore not only cost-effective, but also important for improving the quality of life. A comparison of the safety, tolerability and immunogenicity were performed after vaccination between NBP615 and Gardasil® in 118 healthy female adults and proved as safe, tolerable and immunogenic. Thus, Phase I/ II clinical trial in healthy adult and adolescent female deems warranted to ensure confirmatory safety and immunogenicity results.

Knowledge gap::Two commercially available HPV vaccine, Gardasil, developed by Merck, and Cervarix, developed by GSK, prevent early infections by HPV types 16 and 18, which cause most of the HPV-related cancers. Gardasil also prevents infection by HPV types 6 and 11, both of which genotypes cause 90% of genital warts. Furthermore, Gardasil 9 was approved and available with 5 different serotypes added to Gardasil. Gardasil prevents anal cancer and genital warts, and the vaccine is also effective for men. No efficacy studies were conducted among adolescent population, and duration of protective efficacy were not yet conducted in a controlled manner. Only few safety, and immunogenicity trial has conducted with NBP615 vaccine among children less than 15 years of age.

Relevance: The goal of this phaseI/ II clinical trial is to assess the immunogenicity and safety of NBP615 HPV vaccine among healthy adult female (19-26 years) and adolescent female (9-13 years) to determine the duration of vaccine induced protective efficacy .

Hypothesis (if any): Vaccinating healthy adult aged 19 to 26 and adolescent female aged 9 to 13 with NBP615 human papilloma virus vaccine (HPV) can induce protective immune response.

Objectives:

Primary objective:

1. To assess the safety of NBP615 with respect to solicited (local & systemic) and unsolicited adverse events after each dose of vaccination in healthy adult aged 19 to 26 and adolescent female aged 9 to 13.

2. To assess the immunogenicity of NBP615 focused on the geometric mean titers (GMTs) and seroconversion rates using (SCRs) a VLP (virus-like particle) ELISA and a PBNA (pseudovirion-based neutralization assay) against anti-HPV 6, 11, 16, and 18) in healthy adult aged 19 to 26 and adolescent female aged 9 to 13.

Secondary objectives:

1.To assess the safety of NBP615 with respect to serious AEs during the entire study period in healthy adult aged 19 to 26 and adolescent female aged 9 to 13.

Methods:

This is a randomized, double-blind, active-controlled, phaseI/II clinical trial to enroll 200 healthy female including 80 healthy adult aged 19 to 26 years and 120 adolescents aged 9 to 13 years. In order to confirm the safety, 80 healthy adult should be enrolled first, and the safety of the test product (NBP615) will be confirmed by 2nd vaccination in adults. After that, enrolled of 120 adolescents proceeds. participants who previously agreed to participate in the study will be screened and only those participants who met the inclusion/exclusion criteria will be randomized in to 1:1 to receive test product (NBP615) or reference product (Gardasil pre-filled syringe). Three/ Two doses of 0.5 ml IM injection will be given and two blood sample, pre vaccine and post vaccine 4 weeks after completion of vaccine will be collected to assess the immunogenicity of NBP615 and Gardasil, comparator HPV vaccine. Solicited adverse events occurring up to 7 days after each dose of the investigational product will be collected in the diary card. Unsolicited adverse events occurring up to 28 days after each dose of the investigational product will be collated in the diary card. Serious adverse events will be collected during the entire study period. In addition to this safety data will be collected through the study period by active contact with the study participants by doing home visit or by telephone contact.

Outcome measures/variables:

Safety

• Incidence rate of solicited local adverse events (AEs) within 7 days after each dose of vaccination.

• Incidence rate of solicited systemic AEs within 7 days after each dose of vaccination.

• Incidence rate of unsolicited AEs within 28 days after each dose of vaccination

• Incidence rate of serious AEs during the entire study period

Immunogenicity

• GMT and Seroconversion rate as measured by VLP ELISA for HPV Types 6, 11, 16, 18

• GMT and Seroconversion rate as measured by PBNA for HPV Types 6, 11, 16, 18

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 9 Years to 26 Years

Eligibility

Inclusion Criteria:

Inclusion criteria for female adults aged 19 to 26

1. Healthy female 19 to 26 years of age at the time of the 1st vaccination 2. Participant fully understands study procedures, and voluntarily agrees to participate in the study and follow the study procedure by giving written informed consent.

3. Participant have been identified as negative by urine-HCG test at screening visit and must have agreed to be able to maintain effective contraception throughout the duration of the clinical trial 4. Participant must have agreed to provide study personnel with a telephone number for telephone visit

-Inclusion criteria for adolescents aged 9 to 13

1. Healthy adolescent female 9 to 13 years of aged at the time of first vaccination.

2. Participant's parent/legally acceptable representative (LAR), fully understands study procedures, and voluntarily agrees to participate in the study and follow the study procedure by giving written informed consent.

3. After menarche, participant has been identified as negative by urine-HCG test at screening visit.

Exclusion Criteria:

Exclusion criteria for female adults aged 19 to 26

1. Received a marketed HPV vaccine, or had participated in an HPV vaccine clinical trial and had received either active agent or placebo.

2. Use of any investigational or non-registered product (drug, vaccine or medical device) within 30 days preceding the first dose of study vaccine, or planned use during the study period.

3. Previous or planned administration of any other vaccine within 30 days preceding the first dose of study vaccine.

4. History of hypersensitivity to any component of the study vaccines.

5. History of splenectomy.

6. Currently immunocompromised or was diagnosed as having a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, other autoimmune condition, or other immune disorder which is decided to be medically significant by the investigator.

7. Received immunoglobulins and/or blood product within 3 months preceding the first dose of study vaccine or planned administration during the study period.

8. Receiving or had received chemotherapy, immunosuppressive therapies, or radiation therapy in the year prior to enrolment.

9. Chronic administration (>14 days) of immune-suppressants or immune modulating drugs within 3 months prior to the first vaccine dose or planned administration during the study period. Inhaled, nasal and topical steroids are allowed.

10. Participant with severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.

11. Subject has active cervical disease or a significant history of cervical disease.

12. Fever (Axillary/tympanic temperature > 38°C), within 24 hours prior to the first dose of investigational product.

13. History of alcohol or substance abuse.

14. Any plan to permanently relocate from the area prior to the completion of the study or to leave for an extended period of time when study visits needed to be scheduled.

15. Any condition which in the opinion of the investigator might interfere with the assessment of the study objectives.

Exclusion criteria for adolescent female aged 9 to 13

1. Received a marketed HPV vaccine, or had participated in an HPV vaccine clinical trial and had received either active agent or placebo.

2. Use of any investigational or non-registered product (drug, vaccine or medical device) within 30 days preceding the first dose of study vaccine, or planned use during the study period.

3. Previous or planned administration of any other vaccine within 30 days preceding the first dose of study vaccine.

4. History of hypersensitivity to any component of the study vaccines.

5. History of splenectomy.

6. Currently immunocompromised or was diagnosed as having a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, other autoimmune condition, or other immune disorder which is decided to be medically significant by the investigator.

7. Received immunoglobulins and/or blood product within 3 months preceding the first dose of study vaccine or planned administration during the study period.

8. Receiving or had received chemotherapy, immunosuppressive therapies, or radiation therapy in the year prior to enrolment.

9. Chronic administration (>14 days) of immune-suppressants or immune modulating drugs within 3 months prior to the first vaccine dose or planned administration during the study period. Inhaled, nasal and topical steroids are allowed.

10. Participant with severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.

11. Subject has active cervical disease or a significant history of cervical disease.

12. Fever (tympanic temperature > 38°C), within 24 hours prior to the first dose of investigational product.

13. Any plan to permanently relocate from the area prior to the completion of the study or to leave for an extended period of time when study visits needed to be scheduled

14. Any condition which in the opinion of the investigator might interfere with the assessment of the study objectives.

Related Conditions & MeSH terms

• Human Papilloma Virus Vaccine
• Papilloma

Intervention

Biological:
• NBP615 (SK bioscience HPV vaccine) and Gardasil® (Merck & Co)
NBP615 (purified virus-like particles of HPV types 6, 11, 16, 18). Manufactured by SK bioscience Co., Ltd., Korea. Ingredients included HPV types 6/11/16/18 L1 protein,paque suspension, Prefilled syringe 0.5 mL. Gardasil is a purified virus-like particles of HPV (types 6, 11, 16, 18). Manufactured by Merck & Co. Ingredients included HPV types 6/11/16/18 L1 protein,paque suspension, Prefilled syringe 0.5 mL.

Locations

Country	Name	City	State
Bangladesh	Clinical Trial Unit, icddr,b	Dhaka

Sponsors (2)

Lead Sponsor	Collaborator
International Centre for Diarrhoeal Disease Research, Bangladesh	SK Bioscience Co., Ltd.

Country where clinical trial is conducted

Bangladesh, 

References & Publications (10)

Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections. J Clin Virol. 2005 Mar;32 Suppl 1:S16-24. Review. — View Citation

Burchell AN, Winer RL, de Sanjosé S, Franco EL. Chapter 6: Epidemiology and transmission dynamics of genital HPV infection. Vaccine. 2006 Aug 31;24 Suppl 3:S3/52-61. Epub 2006 Jun 2. Review. — View Citation

Human papillomavirus vaccines. WHO position paper. Wkly Epidemiol Rec. 2009 Apr 10;84(15):118-31. English, French. — View Citation

Lim MC, Moon EK, Shin A, Jung KW, Won YJ, Seo SS, Kang S, Kim JW, Kim JY, Park SY. Incidence of cervical, endometrial, and ovarian cancer in Korea, 1999-2010. J Gynecol Oncol. 2013 Oct;24(4):298-302. doi: 10.3802/jgo.2013.24.4.298. Epub 2013 Oct 2. — View Citation

Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER; Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee — View Citation

Nahar Q, Sultana F, Alam A, Islam JY, Rahman M, Khatun F, Alam N, Dasgupta SK, Marions L, Ashrafunnessa, Kamal M, Cravioto A, Reichenbach L. Genital human papillomavirus infection among women in Bangladesh: findings from a population-based survey. PLoS On — View Citation

Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006 Jun 15;118(12):3030-44. — View Citation

Pisani P, Bray F, Parkin DM. Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer. 2002 Jan 1;97(1):72-81. — View Citation

Sinal SH, Woods CR. Human papillomavirus infections of the genital and respiratory tracts in young children. Semin Pediatr Infect Dis. 2005 Oct;16(4):306-16. Review. — View Citation

Weinstock H, Berman S, Cates W Jr. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex Reprod Health. 2004 Jan-Feb;36(1):6-10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure local injection site reaction and systemic reaction after vaccination	Incidence rate of solicited local (redness, swelling, pain and tenderness) and systemic AEs (fever, vomiting, diarrhoea, fatigue, headache and myalgia) will be measured in two study group.	12 months
Primary	Measure HPV antibody titre before and after vaccination	Measure GMT and seroconversion in pre and post vaccine blood sample by VLP ELISA and PBNA method. .	Will measure antibody titre change between baseline and at 7 months