Clinical Trials

MainTitle

Optimizing HPV Vaccination in Children and Adolescents Living With HIV (OPTIMO)

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified February 2020 by Fred Hutchinson Cancer Research Center

Sponsor
Fred Hutchinson Cancer Research Center

Collaborator
NGO Via Libre
Instituto Fernandes Figueira
National Cancer Institute (NCI)

Information provided by (Responsible Party)
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier
NCT04265950

First received: February 7, 2020
Last updated: February 19, 2020
Last Verified: February 2020
History of Changes
Purpose

Purpose

This study will enroll 9-13 year old children living with HIV from Lima, Peru and Rio de Janeiro, Brazil as well as HIV-uninfected children of the same age group from the same areas. Baseline data collection includes: age, sexual activity status, pregnancy status and HPV antibody serology for all children, as well as HIV viral load, % CD4 or CD4 counts for children living with HIV (CLWH). Eligible CLWH will be block randomized to three interventions arms and HIV uninfected children will be directly enrolled into a fourth control arm. HPV vaccination (Gardasil 9) will be administered as single doses at study visits as follows:

  • Arm 1 (HIV+) receives 3 doses at 0, 2, 6 months
  • Arm 2 (HIV+) receives 2 doses at 0 and 6 months
  • Arm 3 (HIV+) receives 1 dose at 0 month
  • Arm 4 (HIV -) receives 2 doses 0, 6 months All arms receive an anamnestic booster dose
24 months after the last specific regimen vaccine dose to elicit B memory and antibody responses. Arm 3 receives one additional dose at month 30 to complete the 3-dose recommended schedule for CLWH.

Condition Intervention Phase
HPV Vaccination
HIV Infected Children

Biological : HPV 9-valent vaccine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Multicenter, Randomized, Open-label Trial to Establish Optimal Number of Doses for HPV Vaccination in Children and Adolescents Living With HIV

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures

  • Anamnestic immune response (after anamnestic boost) [ Time Frame: 1 month after anamnestic booster dose ]
    Measured as number of Bmem cells elicited after the anamnestic boost vaccine dose, comparing 1-, 2-, & 3-dose regimens among CLWH (Arms 1, 2, & 3).
  • Peak immune response [ Time Frame: 1 month after final intervention vaccine dose ]
    Measured as number of Bmem cells elicited after the final intervention vaccine dose comparing 1-, 2-, & 3-dose regimens among CLWH (Arms 1, 2, & 3)
  • HPV-specific antibody titers [ Time Frame: 1 week after the anamnestic booster dose ]
    Measured after the anamnestic boost vaccine dose, comparing 1-, 2-, & 3-dose regimens among CLWH (Arms 1, 2, & 3).
  • HPV-specific antibody titers [ Time Frame: 1 month after the anamnestic booster dose ]
    Measured after the anamnestic boost vaccine dose, comparing 1-, 2-, & 3-dose regimens among CLWH (Arms 1, 2, & 3).
  • HPV-specific antibody titers [ Time Frame: 1 month after the final intervention vaccine dose ]
    Measured after the final intervention vaccine dose comparing 1-, 2-, & 3-dose regimens among CLWH (Arms 1, 2, & 3).
Secondary Outcome Measures:
  • Anamnestic immune response (after anamnestic boost) [ Time Frame: 1 month after the anamnestic boost vaccine dose ]
    Measured as number of Bmem cells elicited after the anamnestic boost vaccine dose, comparing 2- & 3-dose regimens among CLWH with HIV-uninfected children (Arms 1 vs. 4, 2 vs. 4).
  • Peak immune response [ Time Frame: 1 month after the final intervention vaccine dose ]
    Measured as number of Bmem cells elicited after the final intervention vaccine dose comparing 2- & 3-dose regimens among CLWH with HIV-uninfected children (Arms 1 vs. 4, 2 vs. 4).
  • HPV-specific antibody titers [ Time Frame: 1 week and 1 month after the anamnestic boost vaccine dose ]
    Measured after the anamnestic boost vaccine dose, comparing 2- & 3-dose regimens among CLWH with HIV-uninfected children (Arms 1 vs. 4, 2 vs. 4)
  • HPV-specific antibody titers [ Time Frame: 1 month after the final intervention vaccine dose ]
    Measured after the final intervention vaccine dose comparing 2- & 3-dose regimens among CLWH with HIV-uninfected children (Arms 1 vs. 4, 2 vs. 4).
Other Outcome Measures:
  • Neutralization potency and breadth of monoclonal antibodies (mAbs) cloned from isolated HPV-specific Bmem [ Time Frame: 1 month after anamnestic vaccine dose ]
    Measured after a dose of vaccine given 24 months after the final intervention vaccine dose (1, 2, or 3 doses) across all arms.
  • Long-term (plateau) immune response [ Time Frame: 24 months after the final intervention vaccine dose ]
    Measured as number of Bmems present after the final intervention vaccine dose, comparing 1-, 2-, & 3-dose regimens among CLWH (Arms 1, 2, & 3).
  • Long-term (plateau) immune response [ Time Frame: 24 months after the final intervention vaccine dose ]
    Measured as number of Bmems present after the final intervention vaccine dose, comparing 2- & 3-dose regimens among CLWH with HIV-uninfected children (Arms 1 vs. 4, 2 vs. 4).
  • Number of plasmablast [ Time Frame: 1 week after anamnestic boost ]
    Elicited after anamnestic boost dose, comparing Arms 1, 2, & 3
  • Number of plasmablast [ Time Frame: 1 week after anamnestic boost ]
    Elicited after anamnestic boost dose, comparing 2- & 3-dose regimens among CLWH with HIV-uninfected children (Arms 1 vs. 4, 2 vs. 4)

Estimated Enrollment: 100
Study Start Date: May 2020
Estimated Study Completion Date: July 2024
Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Arm 1 - HIV-infected children
HPV-9 valent vaccine (3 doses)
Biological: HPV 9-valent vaccine

Vaccination with licensed HPV vaccine using several alternative dosing schedules.

Other Name: Gardasil 9
Experimental: Arm 2 HIV-infected children
HPV-9 valent vaccine (2 doses)
Biological: HPV 9-valent vaccine

Vaccination with licensed HPV vaccine using several alternative dosing schedules.

Other Name: Gardasil 9
Experimental: Arm 3 - HIV-infected children
HPV-9 valent vaccine (1 dose)
Biological: HPV 9-valent vaccine

Vaccination with licensed HPV vaccine using several alternative dosing schedules.

Other Name: Gardasil 9
Other: Arm 4 - HIV uninfected children
HPV-9 valent vaccine (2 dose)
Biological: HPV 9-valent vaccine

Vaccination with licensed HPV vaccine using several alternative dosing schedules.

Other Name: Gardasil 9

Detailed Description:

A generation of children living with HIV (CLWH) in Latin America and the Caribbean (LAC) are approaching the age of sexual debut and are, therefore, at risk of infection by oncogenic human papilloma viruses (HPVs). Three virus-like-particle based vaccines are highly efficacious in preventing HPV infections and disease: Cervarix, including types 16 and 18 (2vHPV), Gardasil containing types 6, 11, 16 and 18 (4vHPV), and Gardasil 9 containing types 6, 11, 16, 18, 31, 33, 45, 52 and 58 (9vHPV). Best practice HPV vaccination schedules for HIV-infected children are not known, and alternative dosing schedules may improve immunogenicity and provide better long-term protection. Duration of vaccine response will correlate with elevated anamnestic response measured 24 months after last dose of a given regimen. Importantly, this vaccine trial will take place among CLWH in resource-poor settings, and may have global implications for vulnerable children, who may have low nutritional status, etc., who would most benefit from highly immunogenic and efficient vaccine schedules.
In vaccinating CLWH one of the critical questions is whether the vaccine will provide long term protection from HPV infections. Our studies will focus on the generation of long-lived B cell memory immunity. The investigators will test responses to the following: the standard three-dose regimen recommended by the CDC for CLWH (arm 1: CLWH), the two-dose regimen recommended for immunocompetent adolescents by CDC, Peruvian and Brazilian guidelines (arm 2: CLWH and arm 4: HIV-uninfected youth), and a one-dose regimen (arm 3: CLWH). It is well known that both antibody titers and B cell memory (Bmem) responses peak around one month after the last dose of vaccine then gradually fall and reach a plateau by 18 months post vaccination. Therefore, Bmem responses will be studied at one month after the last vaccine dose and again during the plateau at 24 months past the last vaccine dose. In order to stimulate an anamnestic response a booster dose will be given 24 months after the last dose of each regimen in each arm. Characteristic of an anamnestic response is a very rapid rise in antibody titer accompanied by a burst of plasmablasts. To measure these responses, blood will be collected at 1 and 4 weeks after the booster dose. Comparison of responses in arms 1, 2, and 3 will explore the need for a 3-dose regimen in CLWH. An innovation of this trial is to test, for the first time, the immune response to a reduced number of doses of HPV vaccine in CLWH. The purpose of this study is to find the optimum number of doses of 9vHPV to elicit a robust B cell memory and antibody responses in CLWH. Responses in CLWH will be compared against HIV-uninfected youth who receive the standard 2-dose regimens per CDC Peruvian and Brazilian guidelines.

Eligibility

Eligibility

Ages Eligible for Study: 9 Years to 13 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:

  • Arms 1 - 3: Children must be living with HIV. HIV infection must be confirmed by local algorithm (positive NAAT test before 18 months of age with positive serologic test thereafter). Arm 4: Children must be healthy (without autoimmune disease or cancer) and not living with HIV.
  • Children in Arms 1 - 3 must be on a consistent, clinically appropriate combination ART regimen for >6 months prior to study enrollment.
  • Children must be 9- 13 year old (at or after 9th birthday, prior to 14th birthday). This will allow us to vaccinate participants within the recommended age range for receipt of HPV vaccination in Peru and Brazil.
  • Children in Arms 1, 2, & 3 (CLWH) must have clinical laboratory values as follows within 6 months prior to study entry: CD4% >15% or CD4 counts >200 cells/ mm3 and 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 continue in follow-up.
  • The investigators anticipate that all children will enter the study prior to sexual debut, although this will not be investigated clinically. 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 legal 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 (>10mg/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.
  • Children may not be receiving any other investigational agents during the course of the study.
  • Children in all arms with contraindications for HPV vaccination, or reporting previous HPV immunization. Children with contraindications to vaccination (including pregnancy or breastfeeding) or previous allergic reaction to any vaccines or constituents of vaccines.
  • Children with physical or psychiatric conditions/social situations that would limit compliance with study requirements that in the opinion of the investigator(s) could affect the assessment of study objectives or put volunteers at risk.
  • Children who are enrolled and later found to be seropositive for HPV at study entry
(by Luminex assay performed by the Central Laboratory Core in Seattle) will be discontinued from specimen collection.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT04265950

Contacts

Contact:   Ann Duerr, MD, PhD 2066677938 aduerr@fredhutch.org

Locations

Brazil
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, Brazil, 21040-900
Contact: Beatriz Grinsztejn    55-21-2270-706    gbeatriz@ipec.fiocruz.br
Principal Investigator: Beatriz Grinsztejn
Peru
Asociacion Civil Via Libre
Lima, Peru, 15001
Contact: Robinson Cabello    +51 1 2039900    rcabello@vialibre.org.pe
Principal Investigator: Robinson Cabello

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center
NGO Via Libre
Instituto Fernandes Figueira
National Cancer Institute (NCI)

Investigators

Principal Investigator: Ann Duerr, MD, PhD Fred Hutch/University of Washington Cancer Consortium
More Information

More Information


Responsible Party: Fred Hutchinson Cancer Research Center  
ClinicalTrials.gov Identifier: NCT04265950   History of Changes  
Other Study ID Numbers: RG1007065  
  U54CA242977  
  P30CA015704  
  NCI-2020-01098  
Study First Received: February 7, 2020  
Last Updated: February 19, 2020  
Individual Participant Data    
Plan to Share IPD: No  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  
Product Manufactured in and Exported from the U.S.: Yes  

ClinicalTrials.gov processed this data on June 02, 2020
This information is provided by ClinicalTrials.gov.