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

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

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

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
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.

Study Design

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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

Drug Information available for: Deoxyribonucleic acid

U.S. FDA Resources

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 :

Solicited and unsolicited serious adverse events [ Time Frame: through study completion, an average of 1 year ]
Safety
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
HIV DNA (copies/106 CD4+ T cells) [ Time Frame: Change from Baseline at week 28, 48 ]
Efficacy

Secondary Outcome Measures :

Solicited and unsolicited non-serious adverse events [ Time Frame: through study completion, an average of 1 year ]
Safety
Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA [ Time Frame: Week 24, 36, 48, 60, 72 ]
Efficacy
IUPM from total CD4+ T cells in blood by QVOA [ Time Frame: Week 24, 36, 48, 60, 72 ]
Efficacy
Plasma HIV RNA by SCA [ Time Frame: Week 24, 36, 48, 60, 72 ]
Efficacy
HIV-specific CD8+ and CD4+ T cells [ Time Frame: Week 28, 48 ]
Immunogicity
ADCC [ Time Frame: Week 28, 48 ]
Immunogicity
Binding and neutralizing Ab [ Time Frame: Week 28, 48 ]
Immunogicity
Global gene expression on PBMCs by RNA seq [ Time Frame: Week 28, 48 ]
immune response
Gene expression on HIV-specific CD8+ and CD4+ T cells [ Time Frame: Week 28, 48 ]
immune response

Eligibility Criteria

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:

HIV perinatally infected
Know their HIV+ status
Initiated ART prior to 6 months of age
Male and female ≥ 9 years old
In generally good health
Plasma viral load < 200 copies/ml on ART at screening
CD4 count above 400 cells/mm3 at screening
Participants of childbearing potential who are sexually active must be willing to practice effective contraception during the study
Negative urine β-HCG (human chorionic gonadotropin) pregnancy test for any female of childbearing age (post-menarche)
Availability for follow-up for planned duration of the study
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.
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.
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:

Participants who experienced virological failure necessitating ART modifications
Participants who had ART interruption that lasted >2 weeks
Prior or current pancreatitis or history of alcohol abuse.
Systemic cortisone treatment within the past 30 days
Participants coinfected with chronic hepatitis B (Hepatitis B surface antigen, HBsAg+) or hepatitis C (Hepatitis C antibody, HCV Ab+) at screening
Participants with signs of autoimmune diseases
Participants with history of myocarditis
Participants on any immune modulating or investigational drug
Pregnant or breastfeeding female

Contacts and Locations

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