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Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens With or Without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth (HVRRICANE)

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ClinicalTrials.gov Identifier: NCT04301154
Recruitment Status : Not yet recruiting
First Posted : March 10, 2020
Last Update Posted : March 10, 2020
Sponsor:
Collaborators:
Bambino Gesù Hospital and Research Institute
Henry M. Jackson Foundation for the Advancement of Military Medicine
Johns Hopkins University
University of Miami
Leidos Biomedical Research, Inc.
Case Western Reserve University
Karolinska Institutet
Walter Reed Army Institute of Research (WRAIR)
Armed Forces Research Institute of Medical Sciences, Thailand
University of Padova
Information provided by (Responsible Party):
PENTA Foundation

Brief Summary:
Phase I, Proof of Concept, Open-Label, Randomized Clinical Trial to Evaluate the Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens with or without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth

Condition or disease Intervention/treatment Phase
HIV Infections Biological: HIVIS DNA/MVA-CMDR Biological: HIVIS DNA ± Cervarix and MVA-CMDR Biological: Cervarix Phase 1

Detailed Description:

It can be hypothesized that HIVIS DNA and MVA-CMDR vaccination will lead to a reduction in HIV reservoir markers as a result of vaccine-induced immune responses. The effects may be superior with the addition of TLR4 agonist as immune adjuvant.

In addition, there is also the hypothesis that vaccination with HIVIS DNA and MVA-CMDR several years after the initial HIVIS DNA vaccination in the PEDVAC study will result in strong immune responses.

The study will enroll up to 45 perinatally HIV infected children and youth ≥ 9 years old who are on suppressive antiretroviral therapy (ART).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Proof of Concept, Open-Label, Randomized Clinical Trial to Evaluate the Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens With or Without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Group A
25 study participants aged ≥ 9 years will be enrolled and randomized into arms 1, 2 and 3. They will be from 3 different study sites (Stellenbosch University, Cape Town, South Africa; Chulalongkorn University, Bangkok, Thailand; Children's Hospital Bambino Gesù, Rome, Italy). The rationale for including aged 9 and above is because Cervarix is licensed for age ≥ 9 years.
Biological: HIVIS DNA/MVA-CMDR
HIVIS DNA IM by needle-free injection at weeks 0, 4 and 24 followed by intramuscular (IM) needle injection of MVA-CMDR at weeks 36 and 48 in the same arm as HIVIS DNA.

Biological: HIVIS DNA ± Cervarix and MVA-CMDR

Cervarix IM by needle injection followed by HIVIS DNA IM by a needle-free injection device.

MVA-CMDR IM by needle injection at weeks 36 and 48 in the same arm as HIVIS DNA.


Biological: Cervarix
Cervarix by IM needle injection at weeks 0, 4 and 24.

Experimental: Group B
20 participants will be enrolled to investigate the effects of vaccination with HIVIS DNA ± Cervarix and MVA-CMDR in youth previously enrolled in the PEDVAC study in which 10 had received HIVIS DNA and 10 did not receive vaccine in 2009-2012. They are perinatally HIV-infected and currently being followed at the Children's Hospital Bambino Gesù in Rome. Their median (range) ages are 21 (15 to 25) years old.
Biological: HIVIS DNA/MVA-CMDR
HIVIS DNA IM by needle-free injection at weeks 0, 4 and 24 followed by intramuscular (IM) needle injection of MVA-CMDR at weeks 36 and 48 in the same arm as HIVIS DNA.

Biological: HIVIS DNA ± Cervarix and MVA-CMDR

Cervarix IM by needle injection followed by HIVIS DNA IM by a needle-free injection device.

MVA-CMDR IM by needle injection at weeks 36 and 48 in the same arm as HIVIS DNA.





Primary Outcome Measures :
  1. Solicited and unsolicited serious adverse events [ Time Frame: through study completion, an average of 1 year ]
    Safety

  2. Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells) [ Time Frame: Change from Baseline at week 24, 36, 48, 60, 72 ]
    Efficacy

  3. HIV DNA (copies/106 CD4+ T cells) [ Time Frame: Change from Baseline at week 28, 48 ]
    Efficacy


Secondary Outcome Measures :
  1. Solicited and unsolicited non-serious adverse events [ Time Frame: through study completion, an average of 1 year ]
    Safety

  2. Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA [ Time Frame: Week 24, 36, 48, 60, 72 ]
    Efficacy

  3. IUPM from total CD4+ T cells in blood by QVOA [ Time Frame: Week 24, 36, 48, 60, 72 ]
    Efficacy

  4. Plasma HIV RNA by SCA [ Time Frame: Week 24, 36, 48, 60, 72 ]
    Efficacy

  5. HIV-specific CD8+ and CD4+ T cells [ Time Frame: Week 28, 48 ]
    Immunogicity

  6. ADCC [ Time Frame: Week 28, 48 ]
    Immunogicity

  7. Binding and neutralizing Ab [ Time Frame: Week 28, 48 ]
    Immunogicity

  8. Global gene expression on PBMCs by RNA seq [ Time Frame: Week 28, 48 ]
    immune response

  9. Gene expression on HIV-specific CD8+ and CD4+ T cells [ Time Frame: Week 28, 48 ]
    immune response



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Ages Eligible for Study:   9 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA for Group A:

  1. HIV-1 perinatally infected
  2. Know their own HIV+ status
  3. Initiated ART prior to 6 months of age
  4. Male and female ≥ 9 years old
  5. In generally good health
  6. Plasma viral load < 200 copies/ml on ART at screening
  7. CD4 count above 400 cells/mm3 at screening
  8. Participants of childbearing potential who are sexually active must be willing to practice effective contraception during the study
  9. Negative urine β-HCG (human chorionic gonadotropin) pregnancy test for any female of childbearing age (post-menarche)
  10. Availability for follow-up for planned duration of the study
  11. Passing a test of understanding is required for participants ≥ 18 years old or the parent(s)/legal representative of participant < 18 years old before consent.
  12. Written informed consent from participants ≥ 18 years old or parent(s)/legal representative of participant < 18 years old. Assent by participant aged 9-17 years old will also be required.
  13. Laboratory criteria within 8 weeks prior to enrollment,

    • Hb >11.0 g/dl
    • White blood cell count >3000 cells/mm3
    • Platelets >125,000/ mm3
    • ALT <5 x upper limit of normal
    • Creatinine <1.5 x upper limit of normal

EXCLUSION CRITERIA for Group A:

  1. Participants who experienced virological failure necessitating modifications of ART
  2. Participants who had ART interruption that lasted > 2 weeks
  3. Prior or current pancreatitis or history of alcohol abuse.
  4. Systemic cortisone treatment within the past 30 days
  5. Participants with signs of autoimmune diseases
  6. Participants with history of myocarditis
  7. Participants on any immune modulating or investigational drug
  8. Pregnant or breastfeeding female

INCLUSION CRITERIA for Group B:

  1. HIV-1 perinatally infected
  2. Know their HIV+ status
  3. Previously enrolled in the PEDVAC trial at the Children's Hospital Bambino Gesù in Rome, Italy
  4. Male and female ≥ 9 years old
  5. In generally good health
  6. Plasma viral load < 200 copies/ml on ART at screening
  7. CD4 count above 400 cells/mm3 at screening
  8. Participants of childbearing potential who are sexually active must be willing to practice effective contraception during the study
  9. Negative urine β-HCG (human chorionic gonadotropin) pregnancy test for any female of childbearing age (post-menarche)
  10. Availability for follow-up for planned duration of the study
  11. Passing a test of understanding is required for participants ≥ 18 years old or the parent(s)/legal representative of participant < 18 years old before consent.
  12. Written informed consent from participants ≥ 18 years old or parent(s)/legal representative of participant < 18 years old. Assent by participant aged 9-17 years old will also be required.
  13. Laboratory criteria within 8 weeks prior to enrollment:

    • Hb >11.0 g/dl
    • White blood cell count >3000 cells/mm3
    • Platelets >125,000/ mm3
    • ALT <5 x upper limit of normal
    • Creatinine <1.5 x upper limit of normal

EXCLUSION CRITERIA for Group B:

  1. Prior or current pancreatitis or history of alcohol abuse.
  2. Systemic cortisone treatment within the past 30 days
  3. Participants with signs of autoimmune diseases
  4. Participants with history of myocarditis
  5. Participants on any immune modulating or investigational drug
  6. Pregnant or breastfeeding female
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Responsible Party: PENTA Foundation
ClinicalTrials.gov Identifier: NCT04301154    
Other Study ID Numbers: RV534
First Posted: March 10, 2020    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PENTA Foundation:
HIV reservoir
Perinatally HIV Infected Children
Vaccine
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases