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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 : Recruiting
First Posted : March 10, 2020
Last Update Posted : April 27, 2022
Sponsor:
Collaborators:
Bambino Gesù Hospital and Research Institute
PENTA Foundation
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
Chulalongkorn University
Information provided by (Responsible Party):
Henry M. Jackson Foundation for the Advancement of Military Medicine

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:
HIVIS DNA and MVA-CMDR vaccines induce immune responses important for clearing infected cells: broad HIV-specific CD8+ cytotoxic T cells, potent antibodydependent cellular cytotoxicity (ADCC), and binding antibody (Ab) and neutralizing antibody (NAb). The study include early treated children because of their healthy immunity and small HIV reservoirs. Giving licensed vaccine, Cervarix®, against human papilloma virus (HPV) that contains toll-like receptor (TLR) 4 agonist with HIVIS DNA could increase DNA antigen loading on dendritic cells and promote adaptive immune responses to the HIV vaccine.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 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
Actual Study Start Date : February 18, 2022
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : October 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Vaccines

Arm Intervention/treatment
Experimental: Arm 1 (n=10): HIVIS DNA / MVA-CMDR

Arm 1 (n=10) will receive 1500 micrograms (0.5ml) HIVIS DNA IM by needle-free injection at weeks 0 and 4 followed by intramuscular (IM) needle injection of 1 X 108 IU/mL (1ml) MVA-CMDR at weeks 24 and 36 in the same arm as HIVIS DNA.

Participants who have been randomized to receive HIVIS DNA and MVA-CMDR alone (ARM 1) will be administered Cervarix after week 72, the last study follow-up visit, if required.

Biological: HIVIS DNA/MVA-CMDR
HIVIS DNA IM by needle-free injection at weeks 0 and 4 followed by intramuscular (IM) needle injection of 1 X 108 IU/mL (1ml) MVA-CMDR at weeks 24 and 36 in the same arm as HIVIS DNA.

Experimental: Arm 2 (n=10): HIVIS DNA + Cervarix/ / MVA-CMDR
Arm 2 (n=10) will receive 0.5 ml of Cervarix IM by needle injection followed by 1500 micrograms (0.5ml) per injection of HIVIS DNA IM by a needle-free injection device in the skin above (proximal to) the Cervarix injection (within 1.5 cm). They will receive 1 X 108 IU/mL (1ml) MVA-CMDR IM by needle injection at weeks 24 and 36 in the same arm as HIVIS DNA. They will also receive 0.5 ml Cervarix at the time of the first MVACMDR injection in the opposite arm from the MVA injection at week 24.
Biological: HIVIS DNA + Cervarix and MVA-CMDR
Cervarix IM by needle injection followed by 1500 micrograms (0.5ml) per injection of HIVIS DNA IM by a needle-free injection device in the skin above (proximal to) the Cervarix injection (within 1.5 cm). They will receive 1 X 108 IU/mL (1ml) MVA-CMDR IM by needle injection at weeks 24 and 36 in the same arm as HIVIS DNA. They will also receive 0.5 ml Cervarix at the time of the first MVACMDR injection in the opposite arm from the MVA injection at week 24.

Experimental: Arm 3 (n=5): Cervarix
Arm 3 (n=5) will receive 0.5 ml of Cervarix by IM needle injection at weeks 0, 4 and 24.
Biological: Cervarix
Cervarix by IM needle injection at weeks 0, 4 and 24.




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



Information from the National Library of Medicine

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Ages Eligible for Study:   9 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. HIV perinatally infected
  2. Know their 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 participants < 18 years old before consent.
  12. Written informed consent from participants ≥ 18 years old or parent(s)/legal representative of participants < 18 years old. Assent by participants 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 <1.5 x upper limit of normal
    • Creatinine <1.5 x upper limit of normal

Exclusion criteria:

  1. Participants who experienced virological failure necessitating ART modifications
  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 coinfected with chronic hepatitis B (Hepatitis B surface antigen, HBsAg+) or hepatitis C (Hepatitis C antibody, HCV Ab+) at screening
  6. Participants with signs of autoimmune diseases
  7. Participants with history of myocarditis
  8. Participants on any immune modulating or investigational drug
  9. Pregnant or breastfeeding female

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04301154


Contacts
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Contact: Shaun Barnabas, MD 27 21 938 4295 barnabas@sun.ac.za

Locations
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South Africa
Stellenbosch University Recruiting
Tygerberg Hills, Cape Town, South Africa, 7505
Contact: Shaun Barnabas    27 21 938 6383    barnabas@sun.ac.za   
Sponsors and Collaborators
Henry M. Jackson Foundation for the Advancement of Military Medicine
Bambino Gesù Hospital and Research Institute
PENTA Foundation
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
Chulalongkorn University
Investigators
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Study Chair: Merlin Robb, MD Henry M. Jackson Foundation for the Advancement of Military Medicine
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Responsible Party: Henry M. Jackson Foundation for the Advancement of Military Medicine
ClinicalTrials.gov Identifier: NCT04301154    
Other Study ID Numbers: RV534
First Posted: March 10, 2020    Key Record Dates
Last Update Posted: April 27, 2022
Last Verified: April 2022
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 Henry M. Jackson Foundation for the Advancement of Military Medicine:
HIV reservoir
Perinatally HIV Infected Children
Vaccine
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases