Long-term Immunogenicity of the HIV gp120-NefTat/AS01B Vaccine (GSK SB732461)

NCT03368053 | Completed Phase 1 Results

• 1 other identifier: 201606
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the long-term persistence of binding antibody responses against V1V2 and gp120 in subjects who were vaccinated with the envelope glycoprotein 120 (gp120)-negative factor (Nef)Tat/ Adjuvant System 01B (AS01B) (GSKSB732461) vaccine candidate. Other immune parameters like the HIV-specific cluster of differentiation (CD4+) T cell and CD8+ T cell responses will also be evaluated.

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Keywords

gp120; HIV infections; RV144; gp120-NefTat/AS01B vaccine candidate; V1V2

Outcome Measures

Primary Outcomes (4)

• Number of Subjects With Anti-V1V2 Total Immunoglobulin G (IgG) Binding Antibody Multiplex Assay (BAMA) Response Call

  To comply with BAMA methodology and terminology, the wording "BAMA response call status" was used instead of "seropositivity" in the analysis. Compared to baseline result (Day 0), a sample is called "positive" for a given analyte if the response magnitude is equal to or above (≥) the analyte specific cutoff from all baseline samples in the study (where the cutoff is the 95th percentile of the baseline response, or 100, whichever is higher) OR ≥3 times the response magnitude as compared to the sample specific baseline. The C.1086C\_V1\_V2 Tags strain was not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed.

  At Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14

• Anti-V1V2 Total IgG Antibody BAMA Response Magnitude

  Whenever results were provided as "Mean Fluorescence Intensity (MFI)", the statistical outputs "BAMA response magnitude (MFI)" terminology is used instead of "concentrations/titres". The C.1086C\_V1\_V2 Tags strain was not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed.

  At Day 0, Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14

• Number of Subjects With Anti-V1V2 Subtypes Range: IgG1, IgG2, IgG3 and IgG4 Response Call

  To comply with BAMA methodology and terminology, the wording "BAMA response call status" was used instead of "seropositivity" in the analysis. Compared to baseline result (Day 0), a sample is called "positive" for a given analyte if the response magnitude is equal to or above (≥) the analyte specific cutoff from all baseline samples in the study (where the cutoff is the 95th percentile of the baseline response, or 100, whichever is higher) OR ≥3 times the response magnitude as compared to the sample specific baseline. Antigen IgG3 was assessed for all strains. Antigens IgG1, IgG2 and IgG4 were assessed only for C.1086C\_V1\_V2 Tags strain that was not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed.

  At Day 182, Day 672 historical time point of PRO-HIV-002 and at Year 14

• Anti-V1V2 IgG1, IgG2, IgG3 and IgG4 Antibody BAMA Response Magnitude

  Whenever results were provided as "Mean Fluorescence Intensity (MFI)", the statistical outputs "BAMA response magnitude (MFI)" terminology is used instead of "concentrations/titres". Antigen IgG3 was assessed for all strains. Antigens IgG1, IgG2 and IgG4 were assessed only for C.1086C\_V1\_V2 Tags strain that was not part of any breadth panel. Due to low or infrequent response, or undetectable levels of response among the breadth panel strains, some additional strains, not part of the breadth panels, were also analyzed.

  At Day 0, Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14

Secondary Outcomes (8)

• Number of Subjects With Anti-envelope Glycoprotein (Anti-gp) 120 Total IgG BAMA Response Call

  At Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14

• Anti-gp 120 Total IgG Antibody BAMA Response Magnitude

  At Day 0, Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14

• Number of Subjects With Anti-gp120 (IgG1, IgG2, IgG3 and IgG4) BAMA Response Call for Analytes Not Part of Any Breadth Panel

  At Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14

• Anti-gp120 (IgG1, IgG2, IgG3 and IgG4) BAMA Response Magnitude for Analytes Not Part of Any Breadth Panel

  At Day 0, Day 182, Day 672 historical time points of PRO-HIV-002 and at Year 14

• Frequency of Human Immunodeficiency Virus Type 1 (HIV-1) Specific Cluster of Differentiation-4 (CD4+) T Cells Expressing at Least 2 Cytokine Markers

  At Day 0, Day 98, Day 672 historical time points of PRO-HIV-002 and at Year 14

Study Arms (1)

GSKSB732461 Group

EXPERIMENTAL

Healthy HIV uninfected volunteers who participated in study PRO HIV-002 between February 2003 and February 2005 and who were vaccinated with at least 3 doses of the GSKSB732461 vaccine candidate in the PRO-HIV-002 study.

Procedure: Blood sampling

Interventions

Blood sampling PROCEDURE

Blood samples will be taken during the single study visit at Year 14 for the assessment of: HIV testing, antibody determination, cell mediated immune (CMI) responses and exploratory characterisation.

GSKSB732461 Group

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing any study specific procedure.
• A subject who has received at least 3 doses of the gp120-NefTat/AS01B (GSKSB732461) vaccine candidate in GSK Biologicals-sponsored PRO HIV-002 study.

You may not qualify if:

• Use of any investigational or non-registered product during 30 days prior to study enrolment.
• History of HIV-1 or HIV-2 infection.
• Participation to another clinical trial of an investigational HIV vaccine between study PRO HIV-002 and the present study.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting one month preceding this study. For corticosteroids, this will mean prednisone higher than or equal to (≥) 20 mg/day . Inhaled and topical steroids are allowed.
• Administration of cytotoxic medication within 6 months preceding this study.
• History of daily, long-term immunosuppressive medication between study PRO HIV-002 and the present study.
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before enrolment.
• Any confirmed or suspected immunosuppressive or immunodeficient condition other than HIV disease, based on medical history and physical examination between study PRO HIV-002 and the present study.
• Past administration of an investigational vaccine containing AS01 other than the gp120-NefTat/AS01B (GSKSB732461) vaccine administered in PRO HIV-002 study.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• University Ghent: collaborator

Study Sites (1)

GSK Investigational Site

Ghent, 9000, Belgium

Location

Related Publications (1)

• Van Der Meeren O, Jongert E, Seaton KE, Koutsoukos M, Aerssens A, Brackett C, Debois M, Janssens M, Leroux-Roels G, Mesia Vela D, Sawant S, Yates NL, Tomaras GD, Leroux-Roels I, Roman F. Persistence of vaccine-elicited immune response up to 14 years post-HIV gp120-NefTat/AS01B vaccination. Vaccine. 2020 Feb 11;38(7):1678-1689. doi: 10.1016/j.vaccine.2019.12.058. Epub 2020 Jan 10.

  PMID: 31932137 BACKGROUND

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

877-379-3718

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Descriptive mono-centric study with one single group.

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: December 11, 2017
• Study Start: December 14, 2017
• Primary Completion: January 30, 2018
• Study Completion: January 30, 2018
• Last Updated: October 20, 2020
• Results First Posted: November 18, 2019

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BE (1)