Clinical trial NCT04301154: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV reservoir
Perinatally HIV Infected Children
Vaccine
Lead sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Sponsor class: OTHER
Collaborators: name: Bambino Gesù Hospital and Research Institute
name: PENTA Foundation
name: Johns Hopkins University
name: University of Miami
name: Leidos Biomedical Research, Inc.
name: Case Western Reserve University
name: Karolinska Institutet
name: Walter Reed Army Institute of Research (WRAIR)
name: Armed Forces Research Institute of Medical Sciences, Thailand
name: University of Padova
name: Chulalongkorn University
First posted: 2020-03-10
Enrollment: 25
Sex: ALL
Minimum age (years): 9
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: Solicited and unsolicited serious adverse events
timeFrame: through study completion, an average of 1 year
measure: Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells)
timeFrame: Change from Baseline at week 24, 36, 48, 60, 72
measure: HIV DNA (copies/106 CD4+ T cells)
timeFrame: Change from Baseline at week 28, 48
Secondary outcomes:
measure: Solicited and unsolicited non-serious adverse events
timeFrame: through study completion, an average of 1 year
measure: Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA
timeFrame: Week 24, 36, 48, 60, 72
measure: IUPM from total CD4+ T cells in blood by QVOA
timeFrame: Week 24, 36, 48, 60, 72
measure: Plasma HIV RNA by SCA
timeFrame: Week 24, 36, 48, 60, 72
measure: HIV-specific CD8+ and CD4+ T cells
timeFrame: Week 28, 48
measure: ADCC
timeFrame: Week 28, 48
measure: Binding and neutralizing Ab
timeFrame: Week 28, 48
measure: Global gene expression on PBMCs by RNA seq
timeFrame: Week 28, 48
measure: Gene expression on HIV-specific CD8+ and CD4+ T cells
timeFrame: Week 28, 48
Other outcomes:
Locations:
city: Tygerberg Hills
country: South Africa
facility: Stellenbosch University
state: Cape Town
Study officials:
affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine
name: Merlin Robb, MD
role: STUDY_CHAIR
References: