Establishing Optimal Number of Doses for HPV Vaccination in Children and Adolescents Living With HIV, OPTIMO Trial

HIV Infection Clinical Trial

— OPTIMO  

Official title:

Multicenter, Randomized, Open-Label Trial in Children and Adolescents to Establish Optimal Number of Doses for HPV Vaccination in Children and Adolescents Living With HIV

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04265950
• Other study ID #: RG1007065
• Secondary ID: U54CA242977NCI-2
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: March 10, 2022
• Est. completion date: September 30, 2026

Study information

• Verified date: February 2024
• Source: Fred Hutchinson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase IV trial compares 3 different dosing schedules to find the optimal number of doses for HPV vaccination in children and adolescents living with HIV. Comparing 3 different dosing schedules may help researchers determine whether a single dose of HPV vaccine could be effective in preventing HPV in children and adolescents living with HIV.

Description:

OUTLINE: Participants living with HIV are randomized to one of three arms. HIV-negative participants are assigned to a fourth arm.

ARM 1: Participants living with HIV receive recombinant human papillomavirus nonavalent vaccine intramuscularly (IM) at enrollment, and at 2 and 6 months. Participants also receive recombinant human papillomavirus nonavalent vaccine booster dose IM at 30 months.

ARM 2: Participants living with HIV receive recombinant human papillomavirus nonavalent vaccine IM at enrollment and at 6 months. Participants also receive recombinant human papillomavirus nonavalent vaccine booster dose IM at 30 months.

ARM 3: Participants living with HIV receive recombinant human papillomavirus nonavalent vaccine IM at enrollment. Participants also receive recombinant human papillomavirus nonavalent vaccine booster dose IM at 24 months and recombinant human papillomavirus nonavalent vaccine completion dose IM at 30 months.

ARM 4: Participants without HIV receive recombinant human papillomavirus nonavalent vaccine IM at enrollment. Participants also receive recombinant human papillomavirus nonavalent vaccine booster dose IM at 24 months and recombinant human papillomavirus nonavalent vaccine completion dose IM at 30 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 97
• Est. completion date: September 30, 2026
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 9 Years to 13 Years

Eligibility

Inclusion Criteria:

• ARMS 1-3: Children must be living with HIV. HIV infection documented by positive molecular test or positive serologic test.

• ARM 4: Children must be healthy (e.g., without autoimmune disease or cancer) and not infected with HIV

• ARMS 1-3: Children must be on a consistent, clinically appropriate combination antiretroviral therapy (ART) regimen for > 6 months prior to study enrollment

• Children must be 9-13 years-old (at or after 9th birthday, prior to 14th birthday) at enrollment. This will allow vaccination of participants within the recommended age range for receipt of HPV vaccination in Peru and Brazil. Only children ages 9-11 (at or after 9th birthday, prior to 12th birthday) will be enrolled into arms 3 and 4

• Clinical laboratory values for children in Arms 1, 2, & 3 (CLWH) must be as described below:

• CD4% >15% or CD4 counts >200 cells/ mm3

• VL (<400 copies/mL)

• All female participants must not be pregnant (all females will receive pregnancy tests at all vaccine visits prior to receipt of study vaccine). The effects of Gardasil 9 on the developing human fetus at the recommended therapeutic dose are unknown. If pregnancy is confirmed during the screening process, enrollment will not occur. If pregnancy occurs after the first vaccine dose, additional vaccine doses will not be administered, but the child will remain in study follow-up.

• We anticipate that all children will enter the study prior to sexual debut. Sexual debut will be ascertained by participant questioning in Haiti. Physical examination will not be performed at any of the study sites. Potential participants who report sexual activity will not be enrolled

• Children in all arms must have the ability to understand and the willingness to assent to the study. Parents or guardians must be able to understand and willing to sign a written informed consent document

Exclusion Criteria:

• Children who have a serious illness requiring treatment with systemic medications other than ART (excluding short course oral steroids or inhaled steroid treatment for asthma), are currently under immunomodulatory therapy, received immunosuppressive therapy (> 10 mg/day of prednisone or equivalent for > 1 week) in the 6 months prior to enrollment date

• Children who received any vaccine within 3 weeks prior to enrollment date (these children will be encouraged to enroll after 3 weeks have passed)

• Children who received blood-derived products within 6 months prior to enrollment or planned use during the study period

• Children who weigh less than 18 kilograms

• Children with cancer being treated with chemotherapy or radiation

• Potential participants receiving any other investigational agents may be excluded in the opinion of the supervising physician

• Children in all arms with contraindications to vaccination, including pregnancy or breastfeeding

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Children having received HPV vaccination before study entry

• Children with evidence of sexually transmitted HIV infection

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to HPV vaccination

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Biological:
• Recombinant Human Papillomavirus Nonavalent Vaccine
Given IM

Locations

Country	Name	City	State
Brazil	Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ) STD and AIDS Clinical Research Laboratory	Rio de Janeiro	RJ
Haiti	GHESKIO Center	Port-au-Prince
Peru	Via Libre	Lima

Sponsors (5)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Center	Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), GHESKIO Center, National Cancer Institute (NCI), Via Libre

Countries where clinical trial is conducted

Brazil,  Haiti,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Human papillomavirus type 16 (HPV16) neutralizing antibody geometric mean titers (GMTs) (Arm 1 versus [vs.] Arm 2)	Pseudovirion (PsV)-based neutralization assays will be used to establish HPV 16 neutralizing antibody GMT.	At 24 months after the last dose of each vaccine regimen
Secondary	Human papillomavirus type 18 (HPV18) neutralizing antibody GMTs (Arm 1 vs. Arm 2)	Pseudovirion (PsV)-based neutralization assays will be used to establish HPV 18 neutralizing antibody GMT.	At 24 months after the last dose of each vaccine regimen
Secondary	Change in HPV16 and HPV18 binding antibody median fluorescence intensity-MFI (slope) (Arm 1 vs. Arm 2)	The Luminex immunoassay-based assay will be used to measure HPV 16 and HPV 18 binding antibody MFI.	Between 1 month after the last dose and 18 months after the last dose, and between 18 months and 24 months after the last dose of each vaccine regimen
Secondary	HPV16 and HPV18 neutralizing antibody GMTs (Arm 2 vs. Arm 3)	Pseudovirion (PsV)-based neutralization assays will be used to establish HPV 16 and HPV 18 neutralizing antibody GMT.	At 24 months after the last vaccine dose
Secondary	Change in HPV16 and HPV18 binding antibody MFI (slope) (Arm 2 vs. Arm 3)	The Luminex immunoassay-based assay will be used to measure HPV 16 and HPV 18 binding antibody MFI.	Between 1 month and 18 months after the last vaccine dose, and between 18 months and 24 months after the last vaccine dose
Secondary	Binding antibody MFI to all 9 vaccine HPV types (Arm 2 vs. Arm 3)	Compare the response to a 0, 6- months two-dose schedule vs. a 0, 24-months two-dose schedule in children living with HIV (CLWH). The Luminex immunoassay-based assay will be used to measure HPV 16 and HPV 18 binding antibody MFI, as well as the binding antibody MFI for other HPV types.	At month 7 in Arm 2 and month 25 in Arm 3
Secondary	HPV16 and HPV18 neutralizing antibody GMTs (Arm 3 vs. Arm 4)	Pseudovirion (PsV)-based neutralization assays will be used to establish HPV 16 and HPV 18 neutralizing antibody GMT.	At 24 months after the first (single) vaccine dose
Secondary	Change in HPV16 and HPV18 binding antibody MFI (slope) (Arm 3 vs. Arm 4)	The Luminex immunoassay-based assay will be used to measure HPV 16 and HPV 18 binding antibody MFI.	Between 1 month and 18 months after the single vaccine dose, and between 18 months and 24 months after the first (single) vaccine dose