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

NCT04301154 | Completed Phase 1 DMC

• 1 other identifier: RV534
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Conditions

HIV Infections

Keywords

HIV reservoir; Perinatally HIV Infected Children; Vaccine

Outcome Measures

Primary Outcomes (3)

• Solicited and unsolicited serious adverse events

  Safety

  through study completion, an average of 1 year

• 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

• HIV DNA (copies/106 CD4+ T cells)

  Efficacy

  Change from Baseline at week 28, 48

Secondary Outcomes (9)

• Solicited and unsolicited non-serious adverse events

  through study completion, an average of 1 year

• Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA

  Week 24, 36, 48, 60, 72

• IUPM from total CD4+ T cells in blood by QVOA

  Week 24, 36, 48, 60, 72

• Plasma HIV RNA by SCA

  Week 24, 36, 48, 60, 72

• HIV-specific CD8+ and CD4+ T cells

  Week 28, 48

Study Arms (3)

Arm 1 (n=10): HIVIS DNA / MVA-CMDR

EXPERIMENTAL

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

Arm 2 (n=10): HIVIS DNA + Cervarix/ / MVA-CMDR

EXPERIMENTAL

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

Arm 3 (n=5): Cervarix

EXPERIMENTAL

Arm 3 (n=5) will receive 0.5 ml of Cervarix by IM needle injection at weeks 0, 4 and 24.

Biological: Cervarix

Interventions

HIVIS DNA/MVA-CMDR 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 1 (n=10): HIVIS DNA / MVA-CMDR

HIVIS DNA + Cervarix and MVA-CMDR 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 2 (n=10): HIVIS DNA + Cervarix/ / MVA-CMDR

Cervarix BIOLOGICAL

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

Arm 3 (n=5): Cervarix

Eligibility Criteria

• Age: 9 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Stellenbosch University

Tygerberg Hills, Cape Town, 7505, South Africa

Location

MeSH Terms

Conditions

HIV Infections

Interventions

human papillomavirus vaccine, L1 type 16, 18

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Merlin Robb, MD

  Henry M. Jackson Foundation for the Advancement of Military Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 10, 2020
• Study Start: February 18, 2022
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)