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

HIV Infections Clinical Trial

— HVRRICANE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04301154
• Other study ID #: RV534
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 18, 2022
• Est. completion date: February 28, 2025

Study information

• Verified date: May 2024
• Source: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: February 28, 2025
• Est. primary completion date: October 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years and older

Eligibility

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 ß-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

Related Conditions & MeSH terms

• HIV Infections

Intervention

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

Locations

Country	Name	City	State
South Africa	Stellenbosch University	Tygerberg Hills	Cape Town

Sponsors (12)

Lead Sponsor	Collaborator
Henry M. Jackson Foundation for the Advancement of Military Medicine	Armed Forces Research Institute of Medical Sciences, Thailand, Bambino Gesù Hospital and Research Institute, Case Western Reserve University, Chulalongkorn University, Johns Hopkins University, Karolinska Institutet, Leidos Biomedical Research, Inc., PENTA Foundation, University of Miami, University of Padova, Walter Reed Army Institute of Research (WRAIR)

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Solicited and unsolicited serious adverse events	Safety	through study completion, an average of 1 year
Primary	Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells)	Efficacy	Change from Baseline at week 24, 36, 48, 60, 72
Primary	HIV DNA (copies/106 CD4+ T cells)	Efficacy	Change from Baseline at week 28, 48
Secondary	Solicited and unsolicited non-serious adverse events	Safety	through study completion, an average of 1 year
Secondary	Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA	Efficacy	Week 24, 36, 48, 60, 72
Secondary	IUPM from total CD4+ T cells in blood by QVOA	Efficacy	Week 24, 36, 48, 60, 72
Secondary	Plasma HIV RNA by SCA	Efficacy	Week 24, 36, 48, 60, 72
Secondary	HIV-specific CD8+ and CD4+ T cells	Immunogicity	Week 28, 48
Secondary	ADCC	Immunogicity	Week 28, 48
Secondary	Binding and neutralizing Ab	Immunogicity	Week 28, 48
Secondary	Global gene expression on PBMCs by RNA seq	immune response	Week 28, 48
Secondary	Gene expression on HIV-specific CD8+ and CD4+ T cells	immune response	Week 28, 48