Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Infections

Skin and Connective Tissue Diseases

Rare Diseases

Uterine Cervical Neoplasms

Condylomata Acuminata

Uterine Cervical Dysplasia

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Precancerous Conditions

Cervical Intraepithelial Neoplasia

All Drugs and Chemicals

Vaccines

Immunologic Factors

Participants in this arm would receive 270μg/0.5ml HPV vaccines (6,11,16,18,31,33,45,52,58 Types).

Participants in this arm would receive 60μg/0.5ml HPV vaccines (16,18 Types).

Nonavalent HPV vaccine (270μg/0.5ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

Nonavalent HPV vaccine

Bivalent HPV vaccine (60μg/0.5ml) administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

Bivalent HPV vaccine

Jun Zhang, master

Feng-cai Zhu, master

This phase III clinical study was designed to evaluate the efficacy,immunogenicity and safety of Recombinant Human Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type)(E.Coli) manufactured by Xiamen Innovax Biotech CO., LTD., in healthy women aged 18-45 years old.

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

A Multicenter, Randomized, Double-Blind, Controlled (Bivalent Human Papillomavirus Vaccine (16,18 Type)(E. Coli)) Phase III Clinical Trial to Estimate Efficacy, Immunogenicity and Safty of the Recombinant Human Papillomavirus Vaccine (6,11,16,18,31,33,45,52,58 Type) (E.Coli) in Healthy Women Aged 18 to 45 Years

To evaluate the efficacy of the nine-valent vaccine against this outcome compared with the control vaccine

Detect the level of anti-HPV 16 and 18 specific neutralizing antibodies at one month after the third dose to determine whether nine-valent HPV vaccine is non-inferior to the control bivalent HPV vaccine

Analysis the seroconversion and geometric mean concertration of the type specific antibodies of the 7 types.

safety analysis. To evaluate number of SAEs compared with the control vaccine.

safety analysis. To evaluate number of births and terminations compared with the control vaccine.

safety analysis.To evaluate number of emerging chronic diseases compared with the control vaccine.

Xiamen Innovax Biotech Co., Ltd

Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.

Xiamen University

professor

Immune System Diseases

Symptoms and General Pathology

Papilloma

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Virus Diseases

Syndrome

Communicable Diseases

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

RNA Virus Infections

Slow Virus Diseases

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Three doses of 9vHPV vaccine at the routine dosing schedule of 0/2/6 months

Two doses of 9vHPV vaccine at an expanded dosing schedule of 0/6 months with a third dose given at month 12

Deborah Money, MD

Emma Karlsen, BSc

Dozie Ochular

Sudharsana R Ande, PhD

Vanessa Poliquin, MD

Mariana Rusler, BSc Psych., CCRA

Shariq Haider, MD

Klaudia Szczech, MSc

Arifa Rahman, M.B.B.S, MPH

Mark Yudin, MD

Adriana D'Aquila, R.N.

Sharon Walmsley, MD

Hasna Meddour

Suzanne Taillefer, PhD

Isabelle Boucoiran, MD

Nathalie Paisible, R.N.

Hansi Peiris

Marina Klein, MD

Isabelle Chabot

Geneviève Gagnon, R.N.

Marie-Louise Vachon, MD

Danielle Myrah, RN, BScN

Sarah Craddock, CHIM

Alexander Wong, MD

There are very little data on human papillomavirus (HPV) vaccination among the 18 million women living with HIV (WLWH) globally, who constitute a population most vulnerable to HPV and the resultant cervical cancer. Particularly, there are no data to date on reduced-dose schedules of nonavalent HPV (9vHPV) vaccination in WLWH and there are very little data on the 9vHPV vaccine in this population overall. It is critical to examine the 9vHPV vaccine in WLWH now because the quadrivalent HPV (4vHPV) vaccine has been discontinued. Additionally, in order to reach the World Health Organization's global goal of cervical cancer elimination, we must determine the role of various HPV prevention strategies in this important population including reduced vaccine dosing which can drastically increase the feasibility of HPV vaccination programs globally.

This randomized clinical trial will enrol WLWH aged 18-45 from across Canada who have not previously received an HPV vaccine. Participants will be randomized 1:1 to receive 3 doses of 9vHPV vaccine at the routine vaccine schedule of 0/2/6 months or 2 doses at an expanded schedule of 0/6 months with a third dose at month 12 to adhere to current recommendations for WLWH. We will compare the immune response generated to two versus three doses of 9vHPV vaccine and will follow participants for 2 years to examine the immune response over time.

This study, which builds upon our team's prior work on HPV vaccination in WLWH, will determine whether two doses of 9vHPV vaccine can be used in WLWH instead of three, and will examine additional aspects of HPV vaccination in WLWH including the immune response to three doses, vaccine safety and efficacy, and attitudes towards self-collected HPV samples in this population. These data will inform global public health policy and programming and will inform the global strategy for cervical cancer elimination.

A Study of Reduced Dosing of the Nonavalent HPV Vaccine in Women Living With HIV

Anti-HPV16/18 GMTs at month 7 (1 month post 3rd dose in Group 1 and 1 month post 2nd dose in Group 2)

University of British Columbia

Principle Investigator

3 doses of bivalent HPV vaccine (Cervarix) given at M0, M1 and M6

2 doses of bivalent HPV vaccine (Cervarix) given at M0 and M6

1 dose of bivalent HPV vaccine (Cervarix) given at M0

3 doses of nonavalent HPV vaccine (Gardasil9) given at M0, M2 and M6

2 doses of nonavalent HPV vaccine (Gardasil9) given at M0 and M6

1 dose of nonavalent HPV vaccine (Gardasil9) given at M0

head to head comparisons of different dose schedules and HPV vaccine types

bivalent HPV vaccine

nonavalent HPV vaccine

Deborah Watson-Jones, Dr

Cervical cancer is the most common cancer in women aged 15-44 years in East Africa, and mortality rates are very high. HPV vaccines are most effective if given to girls who have not yet acquired HPV infection. In Tanzania, HPV vaccine has been shown to be safe, acceptable and can be delivered with high coverage (\~80%). However, the cost of delivering HPV vaccine is considerably higher than costs for traditional infant/child vaccinations. This is primarily because of costs to establish outreach programmes and associated personnel costs including nurses who must spend significant time away from their posts to deliver vaccine, especially if multiple doses are needed. There is global interest in simplifying HPV vaccine delivery by reducing the number of doses. If a single dose could be given, this could halve the costs of delivery, making it more accessible to the populations that need it most. Recently, the WHO recommended that 2 doses of HPV vaccine could be given to young girls, based on studies in high and upper middle-income countries. However in Africa high rates of infections like malaria and worms can affect immune responses to vaccines. It is essential to know that reducing the number of doses does not reduce the protective immune response of these vaccines. The investigators are conducting a trial in Tanzanian girls aged 9-14 years to establish whether a single dose of HPV vaccine produces immune responses that are likely to be effective in preventing cervical cancer. Two different HPV vaccines, the bivalent (2-v) vaccine that protects against HPV 16/18 (the cause of 70% of cancers) and the 9-valent (9-v) vaccine that protects against 9 HPV types, will be compared. The trial will randomise 900 girls to 6 arms and follow them for 36 months. Girls will receive the 2-v or the 9-v HPV vaccine, as 1, 2 or 3 doses. Girls receiving 1 or 2 doses will be compared with those receiving 3 doses of the same vaccine, to ensure that the reduced dose regimen produces an immune response that is not inferior to 3 doses. Girls in the 1 and 2 dose arms will be enrolled in an extension and followed for up to 9 years, to examine the stability of immune responses. The immune responses in this study will also be compared with results from other countries where the vaccine has been shown to be protective. This will provide information about whether a reduced number of doses is likely to be protective in Africa. This work will be extremely important in informing future HPV vaccination strategies and will be one of the first randomised trials of 1 and 2 doses of any HPV vaccine in Africa.

Human papillomavirus (HPV) infection is the primary cause of cervical cancer, a major public health problem in Africa. Currently there are three vaccines (Cervarix, Gardasil® and Gardasil-9®) that offer excellent protection against HPV infection with vaccine-related HPV genotypes. The objective of this trial is to demonstrate non-inferiority of immune responses with 1 dose of HPV vaccine compared with the recommended 2 or 3 doses of the same vaccine by evaluating HPV 16/18-specific seropositivity, antibody avidity and memory B cell responses at M36. Specifically, the investigators will determine whether a single dose of the 2-valent HPV vaccine (Cervarix, that protects against HPV 16/18 genotypes) or of a new 9-valent HPV vaccine (Gardasil-9,that protects against HPV 6/11/16/18/31/33/45/52/58) produces immune responses that are non-inferior to those observed with 3 doses of vaccine when given to HIV-negative 9-14 years old girls in a malaria-endemic region of Tanzania.

The trial will also determine whether the World Health Organization's (WHO) recently recommended 2 dose strategy for girls aged under 15 years produces similar immune responses in Sub-Saharan Africa (SSA) compared to the previously recommended 3 dose schedule. In addition, the cost-effectiveness of alternative dosing schedules and of the two vaccines will be explored.

The trial will enrol 900 girls who are resident in Mwanza into an un-blinded, individually-randomised trial with 6 arms. Arm A will comprise participants randomised to receive 3 doses of the 2-valent vaccine, Arm B those randomised to receive 2 doses of the 2-valent vaccine and Arm C those randomised to receive 1 dose of the 2-valent vaccine. Arms D, E and F will be those participants randomised to receive 3, 2 or 1 dose of the 9-valent vaccine, respectively.

The effect of different dose schedules and type of HPV vaccine on a range of immune responses will be measured up to 36 months after the first dose. In a trial extension that will extend follow-up, we will also determine whether the one dose schedule of these vaccines produces non-inferior immune responses to the recommended two dose schedule for up to 108 months, and examine the long-term stability of the immune responses to 9 years after the first dose.

The protocol will be harmonised, and laboratory procedures and immunological endpoints will be cross-validated, with those of a large HPV vaccine dose-reduction efficacy trial being planned by the NIH in Costa Rica to examine the protective effect of the same vaccines given as 1 or 2 doses. This trial will allow the examination of quality and durability of antibody responses, and safety and cost-effectiveness of reduced dose schedules compared to the originally recommended 3 dose schedule in a population with high burden of malaria and other infections that may affect vaccine immune responses.

A Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls

Proportion with HPV 16/18-specific seropositivity

HPV 16/18-specific seropositivity and antibody GMT

HPV 16/18-specific antibody avidity and memory B cell responses

HPV 6/11/31/33/45/52/58-specific antibody seropositivity

HPV 6/11/31/33/45/52/58-specific antibody GMT

incremental financial and economic costs of vaccination, using WHO costing tool

estimates of costs and effects of vaccination will be integrated into an existing HPV cost-effectiveness model (WHO CHOICE)

solicited adverse events considered to have a reasonable possibility of having been contributed to by the vaccine

unsolicited adverse events considered to have a reasonable possibility of having been contributed to by the vaccine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy, Immunogenicity and Safty Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli)	NCT04537156	Cervical Intrae... Cervical Cancer Condylomata Acu...	Nonavalent HPV ... Bivalent HPV va...	18 Years - 45 Years	Xiamen University
A Study of Reduced Dosing of the Nonavalent HPV Vaccine in Women Living With HIV	NCT05495906	HPV Human Papilloma... Human Immunodef...	Nonavalent HPV ...	18 Years - 45 Years	University of British Columbia
A Study of Reduced Dosing of the Nonavalent HPV Vaccine in Women Living With HIV	NCT05495906	HPV Human Papilloma... Human Immunodef...	Nonavalent HPV ...	18 Years - 45 Years	University of British Columbia
A Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls	NCT02834637	Human Papilloma...	bivalent HPV va... nonavalent HPV ...	9 Years - 14 Years	London School of Hygiene and Tropical Medicine

Spots Global Cancer Trial Database for nonavalent hpv vaccine