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

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ClinicalTrials.gov Identifier: NCT04265950
Recruitment Status : Not yet recruiting
First Posted : February 12, 2020
Last Update Posted : March 23, 2021
Sponsor:
Collaborators:
Asociacion Civil Via Libre
Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE February 7, 2020
First Posted Date  ICMJE February 12, 2020
Last Update Posted Date March 23, 2021
Estimated Study Start Date  ICMJE May 2021
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2020)
Human papillomavirus type 16 (HPV16) neutralizing antibody geometric mean titers (GMTs) (Arm 1 versus [vs.] Arm 2) [ Time Frame: At 24 months after the last dose of each vaccine regimen ]
Pseudovirion (PsV)-based neutralization assays will be used to establish HPV 16 neutralizing antibody GMT.
Original Primary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • 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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2020)
  • Human papillomavirus type 18 (HPV18) neutralizing antibody GMTs (Arm 1 vs. Arm 2) [ Time Frame: At 24 months after the last dose of each vaccine regimen ]
    Pseudovirion (PsV)-based neutralization assays will be used to establish HPV 18 neutralizing antibody GMT.
  • Change in HPV16 and HPV18 binding antibody median fluorescence intensity-MFI (slope) (Arm 1 vs. Arm 2) [ Time Frame: 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 ]
    The Luminex immunoassay-based assay will be used to measure HPV 16 and HPV 18 binding antibody MFI.
  • HPV16 and HPV18 neutralizing antibody GMTs (Arm 2 vs. Arm 3) [ Time Frame: At 24 months after the last vaccine dose ]
    Pseudovirion (PsV)-based neutralization assays will be used to establish HPV 16 and HPV 18 neutralizing antibody GMT.
  • Change in HPV16 and HPV18 binding antibody MFI (slope) (Arm 2 vs. Arm 3) [ Time Frame: Between 1 month and 18 months after the last vaccine dose, and between 18 months and 24 months after the last vaccine dose ]
    The Luminex immunoassay-based assay will be used to measure HPV 16 and HPV 18 binding antibody MFI.
  • Binding antibody MFI to all 9 vaccine HPV types (Arm 2 vs. Arm 3) [ Time Frame: At month 7 in Arm 2 and month 25 in 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.
  • HPV16 and HPV18 neutralizing antibody GMTs (Arm 3 vs. Arm 4) [ Time Frame: At 24 months after the first (single) vaccine dose ]
    Pseudovirion (PsV)-based neutralization assays will be used to establish HPV 16 and HPV 18 neutralizing antibody GMT.
  • Change in HPV16 and HPV18 binding antibody MFI (slope) (Arm 3 vs. Arm 4) [ Time Frame: Between 1 month and 18 months after the single vaccine dose, and between 18 months and 24 months after the first (single) vaccine dose ]
    The Luminex immunoassay-based assay will be used to measure HPV 16 and HPV 18 binding antibody MFI.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: February 10, 2020)
  • 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)
 
Descriptive Information
Brief Title  ICMJE Establishing Optimal Number of Doses for HPV Vaccination in Children and Adolescents Living With HIV, OPTIMO Trial
Official Title  ICMJE 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
Brief 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE HIV Infection
Intervention  ICMJE Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
Given IM
Other Names:
  • Gardasil 9
  • Nonavalent HPV VLP Vaccine
  • Recombinant HPV Nonavalent Vaccine
  • Recombinant Human Papillomavirus 9-valent Vaccine
Study Arms  ICMJE
  • Experimental: Arm 1 (3 doses of 9vHPV vaccine)
    Participants living with HIV receive recombinant human papillomavirus nonavalent vaccine IM at enrollment, and at 2 and 6 months. Participants also receive recombinant human papillomavirus nonavalent vaccine booster dose IM at 30 months.
    Intervention: Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
  • Experimental: Arm 2 (2 doses of 9vHPV vaccine)
    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.
    Intervention: Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
  • Experimental: Arm 3 (1 dose of 9vHPV vaccine)
    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.
    Intervention: Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
  • Active Comparator: Arm 4 (1 dose of 9vHPV vaccine)
    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.
    Intervention: Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 10, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2024
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ARMS 1-3: Children must be living with HIV. HIV infection must be confirmed by local algorithm (positive nucleic acid amplification test [NAAT] test before 18 months of age and/or positive serologic test thereafter)
  • 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
  • ARMS 1-3: CD4% > 15% or CD4 counts > 200 cells/mm^3 (within 6 months prior to study entry)
  • ARMS 1-3: Viral load (VL) < 400 copies/mL (within 6 months prior to study entry)
  • 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
  • It is anticipated 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 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 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 the study
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to HPV vaccination
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 9 Years to 13 Years   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Ann Duerr, MD, PhD 206-667-7938 aduerr@fredhutch.org
Listed Location Countries  ICMJE Brazil,   Peru
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04265950
Other Study ID Numbers  ICMJE RG1007065
U54CA242977 ( U.S. NIH Grant/Contract )
NCI-2020-01098 ( Registry Identifier: NCI / CTRP )
10521 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE
  • Asociacion Civil Via Libre
  • Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ)
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ann Duerr, MD, PhD Fred Hutch/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP