A Clinical Trial in Healthy, HIV-1-Uninfected Adult Participants to Compare the Safety, Tolerability and Immunogenicity of CH505TF gp120 Produced From Stably Transfected Cells to CH505TF gp120 Produced From Transiently Transfected Cells

NCT03856996 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 12334569
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to compare the safety, tolerability, and immunogenicity of CH505TF gp120 produced from stably transfected cells to CH505TF gp120 produced from transiently transfected cells in healthy, HIV-1-uninfected adult participants.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (12)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.

  Measured through 7 days after each vaccine dose

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.

  Measured through 7 days after each vaccine dose

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.

  Measured through 7 days after each vaccine dose

• Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) in U/L

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 14, 70, 182, 273

• Chemistry and Hematology Laboratory Measures - Creatinine in mg/dL

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 14, 70, 182, 273

• Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 14, 70, 182, 273

• Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count, Platelets, WBC in 1000 Cells/Cubic mm

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 14, 70, 182, 273

• The Number (Percentage) of Participants With Lab Grade > 1 for ALT, AST, ALP, Creatinine, Hemoglobin, Lymphocyte Count, Neutrophil Count, Platelets, WBC Was Summarized by Arm

  The number (percentage) of participants with lab grade \> 1 for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine, hemoglobin, lymphocyte count, neutrophil count, platelets, white blood cells (WBC) was summarized by arm

  Measured during screening, Days 14, 70, 182, 273

• Adverse Events of Special Interest (AESIs)

  AEs of special interest (AESI) for this protocol include but are not limited to potential immune-mediated diseases. AESI are reported regardless of relationship to study product(s). All AEs are graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.

  Adverse Events of Special Interest (AESI) health contact is at month 18

• Occurrence of HIV-specific Total IgG Binding Antibody Response Elicited by the CH505TF gp120 Proteins Produced Via Transient and Stable Transfection Methods Against the Homologous Proteins

  Serum HIV-1 specific IgG responses were measured on a BioPlex instrument using a standardized custom HIV1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI). Samples were titrated for IgG to CH505TF gp120 (transient transfection) and CH505TF gp120 (stable transfection) at month 0 (Visit 2) and month 6.5 (Visit 7), with a starting 1:50 dilution followed by a 5-fold dilution series. Net MFI less than 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Samples from post-enrollment visits have positive responses if: (1) the net MFI (MFI minus Blank) values were ≥ antigen-specific cutoff at the 1:50 dilution level for IgG, (2) the net MFI values were greater than 3 times the baseline (day 0) net MFI, and (3) the MFI values were greater than 3 times the baseline MFI values.

  Measured at Month 6.5

• Levels of HIV-specific Total IgG Binding Antibody Response Elicited by the CH505TF gp120 Proteins Produced Via Transient and Stable Transfection Methods Against the Homologous Proteins (Measured by Net MFI)

  Serum HIV-1 specific IgG responses were measured on a BioPlex instrument using a standardized custom HIV1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate). Net MFI less than 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Samples from post-enrollment visits have positive responses if: (1) the net MFI (MFI minus Blank) values were ≥ antigen-specific cutoff at the 1:50 dilution level for IgG, (2) the net MFI values were greater than 3 times the baseline (day 0) net MFI, and (3) the MFI values were greater than 3 times the baseline MFI values.

  Measured at Month 6.5

• Area Under Titration Curve of HIV-specific Total IgG Binding Antibody Response Elicited by the CH505TF gp120 Proteins Produced Via Transient and Stable Transfection Methods Against the Homologous Proteins

  Samples were titrated for IgG to CH505TF gp120 (transient transfection) and CH505TF gp120 (stable transfection) at month 0 (Visit 2) and month 6.5 (Visit 7), with a starting 1:50 dilution followed by a 5-fold dilution series, ending at 1:156250 dilution. The AUC value was calculated using the trapezoidal rule based on the raw MFI values truncated at zero across the log base 10 dilution series. For each combination of individual and antigen, AUC at each time point was the sum of the areas of the trapezoids calculated between any non-excluded data points in the analyte/titration. AUC was not calculated for any samples which were incompletely titrated, or where a dilution was missing due to failing QC criteria. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500.

  Measured at Month 6.5

Secondary Outcomes (2)

• Occurrence of Neutralizing Antibody (nAB) Response Against CH505TF gp120 Proteins Produced Via Transient and Stable Transfection Methods

  Measured at Months 2.5 and 6.5

• Neutralization Titers of nAB Responses Against CH505TF gp120 Proteins Produced Via Transient and Stable Transfection Methods

  Measured at Months 2.5 and 6.5

Study Arms (2)

Group 1: Stable CH505TF gp120 + GLA-SE

EXPERIMENTAL

Participants in Group 1 will receive 100 mcg of Stable CH505TF gp120 admixed with 10 mcg of GLA-SE by intramuscular (IM) injection at Months 0, 2, and 6.

Biological: Stable CH505TF gp120; Biological: Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE)

Group 2: Transient CH505TF gp120 + GLA-SE

EXPERIMENTAL

Participants in Group 2 will receive 100 mcg of Transient CH505TF gp120 admixed with 10 mcg of GLA-SE by IM injection at Months 0, 2, and 6.

Biological: Transient CH505TF gp120; Biological: Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE)

Interventions

Stable CH505TF gp120 BIOLOGICAL

Administered by IM injection in the deltoid of the non-dominant arm

Group 1: Stable CH505TF gp120 + GLA-SE

Transient CH505TF gp120 BIOLOGICAL

Administered by IM injection in the deltoid of the non-dominant arm

Group 2: Transient CH505TF gp120 + GLA-SE

Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) BIOLOGICAL

Admixed with Stable CH505TF gp120 or Transient CH505TF gp120 for IM injection in the deltoid of the non-dominant arm

Group 1: Stable CH505TF gp120 + GLA-SE; Group 2: Transient CH505TF gp120 + GLA-SE

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria
• Age of 18 to 50 years
• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Willing to be contacted in person or by phone, text message, or e-mail 6 months after completion of the scheduled clinic visits
• Agrees not to enroll in another study of an investigational research agent before the last required protocol clinic visit
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• HIV-Related Criteria
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit. (see study protocol)
• Hemogram/Complete blood count (CBC)
• Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were assigned female sex at birth, greater than or equal to 13.0 g/dL for volunteers who were assigned male sex at birth. For transgender participants who have been on hormone therapy for more than 6 consecutive months, determine hemoglobin eligibility based on the gender with which they identify (ie, a transgender female who has been on hormone therapy for more than 6 consecutive months should be assessed for eligibility using the hemoglobin parameters for persons assigned female sex at birth).
• White blood cell count equal to 3,300 to 12,000 cells/mm\^3

You may not qualify if:

• General
• Blood products received within 120 days before first vaccination
• Investigational research agents received within 30 days before first vaccination
• Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known hyperlipidemia
• Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 123 study
• Pregnant or breastfeeding
• Active duty and reserve US military personnel
• Vaccines and other Injections
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 123 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 123 PSRT will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made by the HVTN 123 PSRT for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 123 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 123 PSRT on a case-by-case basis.
• Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
• Immune System

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Related Publications (2)

• Wilson GJ, Church LWP, Kelley CF, Robinson ST, Lu Y, Furch BD, Fong Y, Paez CA, Yacovone M, Jacobsen T, Maughan M, Martik D, Heptinstall JR, Zhang L, Montefiori DC, Tomaras GD, Kublin JG, Corey L. HVTN 123: A Phase 1, Randomized Trial Comparing Safety and Immunogenicity of CH505TF gp120 Produced by Stably and Transiently Transfected Cell Lines. J Infect Dis. 2025 Apr 15;231(4):e764-e769. doi: 10.1093/infdis/jiae558.

  PMID: 39671174 DERIVED

• Wolfe LS, Smedley JG 3rd, Bubna N, Hussain A, Harper R, Mostafa S. Development of a platform-based approach for the clinical production of HIV gp120 envelope glycoprotein vaccine candidates. Vaccine. 2021 Jun 29;39(29):3852-3861. doi: 10.1016/j.vaccine.2021.05.073. Epub 2021 Jun 4.

  PMID: 34099325 DERIVED

MeSH Terms

Conditions

HIV Infections

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

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Greg Wilson

  Vanderbilt Medical Center

  STUDY CHAIR

• Colleen Kelley

  Emory University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 27, 2019
• Study Start: May 23, 2019
• Primary Completion: March 16, 2021
• Study Completion: September 7, 2021
• Last Updated: July 12, 2024
• Results First Posted: July 11, 2022

Record last verified: 2024-04

Locations

US (3)