HPV Vaccination in HIV Infected and HIV Uninfected Adolescents in Eswatini

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04982614

Collaborator

(none)

1,400

Enrollment

Locations

Arms

Anticipated Duration (Months)

175

Patients Per Site

12.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multi-site, open-label non-inferiority study of the 9vHPV vaccine among a population of children, adolescents and young women living with HIV in Eswatini. This protocol seeks to assess immunogenicity of a two-dose 9vHPV vaccine regimen among girls and boys (9-14 years) and young women (15-26 years) living with HIV on antiretroviral therapy versus a three-dose 9vHPV vaccine regimen among HIV uninfected young women (15-26 years) in Eswatini. The secondary objectives include examining the safety profiles of the two-dose 9vHPV regimen in those living with HIV and the three-dose 9vHPV regimen in HIV-uninfected young women, as well as measuring the completion of the vaccination series among those living with HIV and those who are not infected with HIV.

Condition or Disease	Intervention/Treatment	Phase
HPV Infection Hiv HPV Vaccine	Biological: Gardasil ® 9	Phase 4

Detailed Description

Cervical cancer remains a significant threat to public health worldwide and remains the leading cause of cancer-associated mortality in women in Sub Saharan Africa. Cervical cancer-associated morbidity and mortality is preventable through HPV vaccination, and screening and treatment of pre-cancerous lesions. To date, there is no nationwide HPV vaccination program in Eswatini and the country is not eligible for Global Alliance for Vaccines and Immunization (GAVI) procurement of HPV vaccines, and yet the triad of HIV, sexually transmitted infections (STI) and cervical cancer generates a severe disease burden warranting immediate introduction of this intervention. Given the global limitations in vaccine supply and the high cost for procurement, country programs, including in Eswatini, must optimize vaccine resources in order to maximize HPV vaccine coverage.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1400 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Multi-site, Open-label Non-inferiority Trial to Assess Immunogenicity of Two Doses of the Nonavalent Human Papillomavirus (HPV) Vaccine Among Children, Adolescents and Young Adults (9-26 Years) Living With HIV vs Three Doses of Nonavalent HPV Vaccine Among HIV Uninfected Young Women (15-26 Years) in Eswatini

Actual Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

May 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2-dose regimen group Boys and girls (aged 9-14 years) and young women (aged 15-26 years) living with HIV will receive a two-dose regimen of the HPV vaccine at baseline (Month 0) and Month 6.	Biological: Gardasil ® 9 GARDASIL 9 is a vaccine indicated in girls and women 9 through 45 years of age for the prevention of the following diseases: Cervical, vulvar, vaginal, and anal cancer, and Genital warts (condyloma acuminata) caused by Human Papillomavirus (HPV). 0.5-mL suspension for intramuscular injection as a single-dose vial and prefilled syringe at the following regimen/schedule: 9 through 14 years - 2-dose at 0, 6 to 12 months OR 3-dose at 0, 2, 6 months 15 through 45 years - 3-dose at 0, 2, 6 months Other Names: Human Papillomavirus 9-valent Vaccine, Recombinant 9vHPV vaccine
Active Comparator: 3-dose regimen group (SOC) HIV-uninfected young women (aged 15-26 years) will receive the standard of care three-dose regimen of the HPV vaccine at baseline (Month 0), Month 2 and Month 6.	Biological: Gardasil ® 9 GARDASIL 9 is a vaccine indicated in girls and women 9 through 45 years of age for the prevention of the following diseases: Cervical, vulvar, vaginal, and anal cancer, and Genital warts (condyloma acuminata) caused by Human Papillomavirus (HPV). 0.5-mL suspension for intramuscular injection as a single-dose vial and prefilled syringe at the following regimen/schedule: 9 through 14 years - 2-dose at 0, 6 to 12 months OR 3-dose at 0, 2, 6 months 15 through 45 years - 3-dose at 0, 2, 6 months Other Names: Human Papillomavirus 9-valent Vaccine, Recombinant 9vHPV vaccine

Arm

Intervention/Treatment

Experimental: 2-dose regimen group

Boys and girls (aged 9-14 years) and young women (aged 15-26 years) living with HIV will receive a two-dose regimen of the HPV vaccine at baseline (Month 0) and Month 6.

Biological: Gardasil ® 9

GARDASIL 9 is a vaccine indicated in girls and women 9 through 45 years of age for the prevention of the following diseases: Cervical, vulvar, vaginal, and anal cancer, and Genital warts (condyloma acuminata) caused by Human Papillomavirus (HPV). 0.5-mL suspension for intramuscular injection as a single-dose vial and prefilled syringe at the following regimen/schedule: 9 through 14 years - 2-dose at 0, 6 to 12 months OR 3-dose at 0, 2, 6 months 15 through 45 years - 3-dose at 0, 2, 6 months

Other Names:

Human Papillomavirus 9-valent Vaccine, Recombinant

9vHPV vaccine

Active Comparator: 3-dose regimen group (SOC)

HIV-uninfected young women (aged 15-26 years) will receive the standard of care three-dose regimen of the HPV vaccine at baseline (Month 0), Month 2 and Month 6.

Biological: Gardasil ® 9

Other Names:

Human Papillomavirus 9-valent Vaccine, Recombinant

9vHPV vaccine

Outcome Measures

Primary Outcome Measures

Anti-HPV geometric mean antibody titers [Month 7 (4 weeks post Month 6 vaccine dose)]
Serum antibodies against HPV antigens (IgG, IFNg, TNF, IL2, CXCL10, granzyme, perforin, PTX3). Geometric mean titers will be summarized by treatment group, and the ratios of mean GMTs between treatment and control and their 95% confidence intervals calculated around point estimates.
Number of seroconversions [Month 7 (4 weeks post Month 6 vaccine dose)]
Number of participants who seroconvert, defined as having no HPV antibodies pre-vaccination, but detectable HPV antibodies at 4 weeks post month 6 vaccine dose

Secondary Outcome Measures

Number of participants with serious adverse events (SAE) [Up to 6 months]
Number of participants who reported experiences of SAE. SAE is defined as those that experienced death, life-threatening conditions or hospitalizations.
Number of participants completing vaccination series [Up to 6 months]
Number of eligible participants completing the 2-dose or 3-dose regimens will be tallied.

Eligibility Criteria

Criteria

Ages Eligible for Study:

9 Years to 26 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

For people living with HIV receiving two-dose regimen:

Females 9-26 years and males 9-14 years,
Documented HIV infection,
Aware of HIV+ status,
Currently receiving antiretroviral treatment (ART) for HIV infection for at least six months,
Living in Eswatini,
For individuals 18+ years: able to provide informed consent,
For individuals 15-17 years: able to provide informed assent,
For individuals 9-14 years of age: able to provide informed assent AND accompanied by an adult caregiver who is able to give informed consent,
Intending to remain in the vicinity of the study sites for the study period

For reference group of HIV-uninfected women receiving three-dose regimen:

Females 15-26 years,
Documented negative HIV test at baseline
Living in Eswatini,
Able to provide informed assent (15-17 years) or informed consent (18-26 years)
Intending to remain in the vicinity of the study sites for the study period

Exclusion Criteria:

For all participants:

Diagnosis of other immunosuppressive diseases or receipt of immunosuppressive medications,
Diagnosis of other acute or chronic illness,
Receipt of other vaccinations within 2-3 weeks before or after study vaccination,
Receipt of blood-derived products within 6 months before or during the study,
Previous receipt of an HPV vaccine,
Currently pregnant,
Known allergies to a vaccine component

Contacts and Locations

Locations

	Site	City	Country
1	Bulembu Clinic	Bulembu	Swaziland
2	Hlathikhulu Government Hospital	Hlatikulu	Swaziland
3	AHF Lamvelase	Manzini	Swaziland
4	AHF Manzini	Manzini	Swaziland
5	Raleigh Fitkin Memorial Hospital	Manzini	Swaziland
6	AHF Matsapha	Matsapha	Swaziland
7	Baylor College of Medicine - Bristol Myers-Squibb Children's Clinical Centre of Excellence	Mbabane	Swaziland
8	Good Shephard Hospital	Siteki	Swaziland