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

NCT ID: NCT04301154

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-18
• Study Completion Date: 2023-10-16

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

HIVIS DNA/MVA-CMDR

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

HIVIS DNA + Cervarix and MVA-CMDR

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

Cervarix

Intervention Type: BIOLOGICAL

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

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Cervarix

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

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 9 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role: collaborator

PENTA Foundation

NETWORK

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: collaborator

Leidos Biomedical Research, Inc.

INDUSTRY

Sponsor Role: collaborator

Case Western Reserve University

OTHER

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: collaborator

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

Armed Forces Research Institute of Medical Sciences, Thailand

OTHER_GOV

Sponsor Role: collaborator

University of Padova

OTHER

Sponsor Role: collaborator

Chulalongkorn University

OTHER

Sponsor Role: collaborator

Henry M. Jackson Foundation for the Advancement of Military Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Merlin Robb, MD

Role: STUDY_CHAIR

Henry M. Jackson Foundation for the Advancement of Military Medicine

Locations

Stellenbosch University

Tygerberg Hills, Cape Town, South Africa

Countries

South Africa

Other Identifiers

RV534

Identifier Type: -

Identifier Source: org_study_id