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HVRRICANE: 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

Sponsor
Henry M. Jackson Foundation for the Advancement of Military Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT04301154
Collaborator
Bambino Gesù Hospital and Research Institute (Other), PENTA Foundation (Other), Johns Hopkins University (Other), University of Miami (Other), Leidos Biomedical Research, Inc. (Industry), Case Western Reserve University (Other), Karolinska Institutet (Other), Walter Reed Army Institute of Research (WRAIR) (U.S. Fed), Armed Forces Research Institute of Medical Sciences, Thailand (Other), University of Padova (Other), Chulalongkorn University (Other)
25
Enrollment
1
Location
3
Arms
20.4
Anticipated Duration (Months)
1.2
Patients Per Site Per Month

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Feb 18, 2022
Anticipated Primary Completion Date :
Oct 31, 2023
Anticipated Study Completion Date :
Oct 31, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Solicited and unsolicited serious adverse events [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) [Change from Baseline at week 24, 36, 48, 60, 72]

    Efficacy

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

    Efficacy

Secondary Outcome Measures

  1. Solicited and unsolicited non-serious adverse events [through study completion, an average of 1 year]

    Safety

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

    Efficacy

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

    Efficacy

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

    Efficacy

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

    Immunogicity

  6. ADCC [Week 28, 48]

    Immunogicity

  7. Binding and neutralizing Ab [Week 28, 48]

    Immunogicity

  8. Global gene expression on PBMCs by RNA seq [Week 28, 48]

    immune response

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

    immune response

Eligibility Criteria

Criteria

Ages Eligible for Study:
9 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Stellenbosch University Tygerberg Hills Cape Town South Africa 7505

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

  • Study Chair: Merlin Robb, MD, Henry M. Jackson Foundation for the Advancement of Military Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Henry M. Jackson Foundation for the Advancement of Military Medicine
ClinicalTrials.gov Identifier:
NCT04301154
Other Study ID Numbers:
  • RV534
First Posted:
Mar 10, 2020
Last Update Posted:
Apr 27, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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:
HIV Infections

Study Results

No Results Posted as of Apr 27, 2022