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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)

Primary Purpose

HIV Infections

Status

Recruiting

Phase

Phase 1

Locations

South Africa

Study Type

Interventional

Intervention

HIVIS DNA/MVA-CMDR

HIVIS DNA + Cervarix and MVA-CMDR

Cervarix

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV reservoir, Perinatally HIV Infected Children, Vaccine

Eligibility Criteria

9 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stellenbosch UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

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

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

Arm 3 (n=5): Cervarix

Arm Description

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.

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.

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

Outcomes

Primary Outcome Measures

Solicited and unsolicited serious adverse events

Safety

Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells)

Efficacy

HIV DNA (copies/106 CD4+ T cells)

Efficacy

Secondary Outcome Measures

Solicited and unsolicited non-serious adverse events

Safety

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

Efficacy

IUPM from total CD4+ T cells in blood by QVOA

Efficacy

Plasma HIV RNA by SCA

Efficacy

HIV-specific CD8+ and CD4+ T cells

Immunogicity

ADCC

Immunogicity

Binding and neutralizing Ab

Immunogicity

Global gene expression on PBMCs by RNA seq

immune response

Gene expression on HIV-specific CD8+ and CD4+ T cells

immune response

Full Information

NCT ID

NCT04301154

First Posted

March 2, 2020

Last Updated

April 20, 2022

Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

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

1. Study Identification

Unique Protocol Identification Number

NCT04301154

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 18, 2022 (Actual)

Primary Completion Date

October 31, 2023 (Anticipated)

Study Completion Date

October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

HIV reservoir, Perinatally HIV Infected Children, Vaccine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Arm 3 (n=5): Cervarix

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

HIVIS DNA/MVA-CMDR

Intervention Description

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

Intervention Name(s)

HIVIS DNA + Cervarix and MVA-CMDR

Intervention Description

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

Intervention Name(s)

Cervarix

Intervention Description

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

Primary Outcome Measure Information:

Title

Solicited and unsolicited serious adverse events

Description

Safety

Time Frame

through study completion, an average of 1 year

Title

Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells)

Description

Efficacy

Time Frame

Change from Baseline at week 24, 36, 48, 60, 72

Title

HIV DNA (copies/106 CD4+ T cells)

Description

Efficacy

Time Frame

Change from Baseline at week 28, 48

Secondary Outcome Measure Information:

Title

Solicited and unsolicited non-serious adverse events

Description

Safety

Time Frame

through study completion, an average of 1 year

Title

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

Description

Efficacy

Time Frame

Week 24, 36, 48, 60, 72

Title

IUPM from total CD4+ T cells in blood by QVOA

Description

Efficacy

Time Frame

Week 24, 36, 48, 60, 72

Title

Plasma HIV RNA by SCA

Description

Efficacy

Time Frame

Week 24, 36, 48, 60, 72

Title

HIV-specific CD8+ and CD4+ T cells

Description

Immunogicity

Time Frame

Week 28, 48

Title

ADCC

Description

Immunogicity

Time Frame

Week 28, 48

Title

Binding and neutralizing Ab

Description

Immunogicity

Time Frame

Week 28, 48

Title

Global gene expression on PBMCs by RNA seq

Description

immune response

Time Frame

Week 28, 48

Title

Gene expression on HIV-specific CD8+ and CD4+ T cells

Description

immune response

Time Frame

Week 28, 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

9 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Shaun Barnabas, MD

Phone

27 21 938 4295

barnabas@sun.ac.za

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Merlin Robb, MD

Organizational Affiliation

Henry M. Jackson Foundation for the Advancement of Military Medicine

Official's Role

Study Chair

Facility Information:

Facility Name

Stellenbosch University

City

Tygerberg Hills

State/Province

Cape Town

ZIP/Postal Code

7505

Country

South Africa

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shaun Barnabas

Phone

27 21 938 6383

barnabas@sun.ac.za

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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