Evaluating the Safety and Immunogenicity of EnvSeq-1 and CH505 M5 gp120 Envs Adjuvanted With GLA-SE in Healthy, HIV-Uninfected Adults

NCT03220724 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 11512042
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of EnvSeq-1 and CH505 M5 gp120 Envs adjuvanted with GLA-SE in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (27)

• Part A: Number of Participants Reporting Local Reactogenicity Signs and Symptoms During the Vaccine Regime

  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 Month Measured through 7 days after the vaccination at Month 0, 2, 4, 8, 12

• Part A: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms During the Vaccine Regime

  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 Month Measured through 7 days after the vaccination at Month 0, 2, 4, 8, 12

• Part A: Number of Participants With Early Study Termination Associated With an Adverse Event (AE) or Reactogenicity During the Vaccine Regime

  From the study termination form, early termination reasons associated with an AE or reactogenicity are tabulated by treatment arm

  Measured through Month 24

• Part A: Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity

  From the study product discontinuation form, study product administration reasons are tabulated by treatment arm

  Measured through the Month 12 boost

• Part A: Chemistry and Hematology Laboratory Measures, for Each Boost: Alkaline Phosphatase, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) in U/L

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, 8, 12, and at Month 15

• Part A: Chemistry and Hematology Laboratory Measures, for Each Boost: Hemoglobin, Creatinine in g/dL

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, 8, 12, and at Month 15

• Part A: Chemistry and Hematology Laboratory Measures, for Each Boost: White Blood Cell (WBC), Platelets, Lymphocytes, Neutrophils

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, 8, 12, and at Month 15

• Part A: Occurrence of HIV-specific Immunoglobulin G (IgG) Responses 2 Weeks After the Third Vaccination With CH505TF gp120

  Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  Measured at Month 4.5

• Part A: Level of HIV-specific IgG Responses 2 Weeks After the Third Vaccination With CH505TF gp120

  Serum HIV-1-specific IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  Measured at Month 4.5

• Part A: Occurrence of HIV-specific Immunoglobulin A (IgA) Responses 2 Weeks After the Third Vaccination With CH505TF gp120

  Serum HIV-1-specific IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  Measured at Month 4.5

• Part A: Level of HIV-specific IgA Responses 2 Weeks After the Third Vaccination With CH505TF gp120

  Serum HIV-1-specific IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI less than 1 is set to 1. The measure unit fluorescence units are relative to assay background, not relative to the placebo arm. Background is used here rather than negative control stimulation, since the antigens are used as bead coating rather than stimulation.

  Measured at Month 4.5

• Number of Part B Participants Reporting Local 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 Month Measured through Month Measured through 7 days after the vaccination at Month 0, 2, 4, 8

• Number of Part B 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 Month Measured through Month Measured through 7 days after the vaccination at Month 0, 2, 4, 8

• Part B: Number of Participants With Early Study Termination Associated With an AE or Reactogenicity During the Vaccine Regime

  From the study termination form, early termination reasons associated with an AE or reactogenicity are tabulated by treatment arm

  Measured through Month 20

• Number of Part B Participants With Study Product Discontinuation Associated With an AE or Reactogenicity

  From the study product discontinuation form, study product administration reasons are tabulated by treatment arm

  Measured through the Month 8 boost

• Part B Chemistry and Hematology Laboratory Measures, for Each Boost: Alkaline Phosphatase, AST, ALT in U/L

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, 8, and at Month 11

• Part B Chemistry and Hematology Laboratory Measures, for Each Boost: Hemoglobin, Creatinine in g/dL

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, 8, and at Month 11

• Part B Chemistry and Hematology Laboratory Measures

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, 8, and at Month 11

• Part B Magnitude and Breadth of Neutralizing Antibody Response Against Autologous Viral Isolates and Related CH103 and CH235 Precursor Detection Isolates 2 Weeks After the Fourth Vaccinations

  Magnitude-breadth characterize the magnitude (ID50) and breadth (number of virus isolates) of each individual serum sample assayed against a panel of virus isolates. MB curves show, for each possible magnitude threshold, the proportion of isolates among the virus panel with magnitudes greater than this threshold. The area under the magnitude-breadth curve (AUC-MB) integrates magnitude and breadth information and provides effective tools to display, summarize, and compare multi-viral immunological data in the context of HIV-1 vaccine trials.

  Measured at Month 8.5

• Part B Magnitude and Breadth of Neutralizing Antibody Responses Against a Panel of Heterologous Tier 2 Isolates Induced 2 Weeks After the Fourth Vaccinations

  Magnitude-breadth characterize the magnitude (ID50) and breadth (number of virus isolates) of each individual serum sample assayed against a panel of virus isolates. MB curves show, for each possible magnitude threshold, the proportion of isolates among the virus panel with magnitudes greater than this threshold. The area under the magnitude-breadth curve (AUC-MB) integrates magnitude and breadth information and provides effective tools to display, summarize, and compare multi-viral immunological data in the context of HIV-1 vaccine trials.

  Measured at Month 8.5

• Number of Part C Participants Reporting Local 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 Month Measured through Month Measured through 7 days after the vaccination at Month 0, 2, 4

• Number of Part C 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 Month Measured through Month Measured through 7 days after the vaccination at Month 0, 2, 4

• Part C: Number of Participants With Early Study Termination Associated With an AE or Reactogenicity During the Vaccine Regime

  From the study termination form, early termination reasons associated with an AE or reactogenicity are tabulated by treatment arm

  Measured through Month 16

• Number of Part C Participants With Study Product Discontinuation Associated With an AE or Reactogenicity

  From the study product discontinuation form, study product administration reasons are tabulated by treatment arm

  Measured through the Month 4 administration

• Part C Chemistry and Hematology Laboratory Measures, for Each Boost: Alkaline Phosphatase, AST, ALT in U/L

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, and at Month 10

• Part C Chemistry and Hematology Laboratory Measures, for Each Boost: Hemoglobin, Creatinine in g/dL

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, and at Month 10

• Part C Chemistry and Hematology Laboratory Measures

  Laboratory results are summarized by analyte and timepoint. Analytes and timepoint combinations with no grade 1 or higher results are not shown.

  Measured during screening, and 2 weeks after each vaccination at Month 0, 2, 4, and at Month 10

Secondary Outcomes (23)

• Part C Magnitude and Breadth of Neutralizing Antibody Response Against Autologous Viral Isolates and Related CH103 and CH235 Precursor Detection Isolates 2 Weeks After the Third (Final) Vaccination

  Measured at Month 4.5

• Part C Magnitude and Breadth of Neutralizing Antibody Responses Against a Panel of Heterologous Tier 2 Isolates Induced 2 Weeks After the Third (Final) Vaccination

  Measured at Month 4.5

• Part A: Occurence of Memory B Cells Differentially Binding to the CH505 Wildtype gp120 TF Env vs the Mutant CH505 Env I Delta 371 gp120 2 Weeks After the Third Vaccination With CH505TF gp120

  Measured at Month 4.5

• Part A: Level of Memory B Cells Differentially Binding to the CH505 Wildtype gp120 TF Env vs the Mutant CH505 Env I Delta 371 gp120 2 Weeks After the Third Vaccination With CH505TF gp120

  Measured at Month 4.5

• Part A: Magnitude and Breadth of Neutralizing Antibody Responses Against Autologous Viral Isolates as Assessed by Area Under the Magnitude-breadth Curves 2 Weeks After the Third Vaccination With CH505TF gp120

  Measured at Month 4.5

Study Arms (9)

Part A: Group 1

EXPERIMENTAL

Participants will receive 20 mcg of CH505TF (admixed with GLA-SE) at Months 0, 2, 4, 8, and 12.

Biological: CH505TF; Biological: GLA-SE adjuvant

Part A: Group 2

EXPERIMENTAL

Participants will receive 100 mcg of CH505TF (admixed with GLA-SE) at Months 0, 2, 4, 8, and 12.

Biological: CH505TF; Biological: GLA-SE adjuvant

Part A: Group 3

EXPERIMENTAL

Participants will receive 400 mcg of CH505TF (admixed with GLA-SE) at Months 0, 2, 4, 8, and 12.

Biological: CH505TF; Biological: GLA-SE adjuvant

Part A: Group 4

PLACEBO COMPARATOR

Participants will receive placebo at Months 0, 2, 4, 8, and 12.

Biological: Placebo

Part B: Group 5

EXPERIMENTAL

Participants will receive CH505TF at Month 0; CH505w53 at Month 2; and CH505w78 at Months 4, and 8. GLA-SE adjuvant is admixed with all the CH505 gp120 proteins.

Biological: CH505TF; Biological: CH505w53; Biological: CH505w78; Biological: GLA-SE adjuvant

Part B: Group 6

EXPERIMENTAL

Participants will receive CH505TF at Month 0; CH505TF and CH505w53 at Month 2; CH505TF, CH505w53, and CH505w78 at Month 4; CH505w53 and CH505w78 at Month 8. GLA-SE adjuvant is admixed with all the CH505 gp120 proteins.

Biological: CH505TF; Biological: CH505w53; Biological: CH505w78; Biological: GLA-SE adjuvant

Part B: Group 7

EXPERIMENTAL

Participants will receive CH505 M5 (admixed with GLA-SE) at Months 0, 2, 4, and 8.

Biological: CH505 M5; Biological: GLA-SE adjuvant

Part B: Group 8

PLACEBO COMPARATOR

Participants will receive placebo at Months 0, 2, 4, and 8.

Biological: Placebo

Part C: Group 9

EXPERIMENTAL

Participants will receive CH505TF at Month 0; CH505w53 at Month 2; and CH505w78 at Months 4.

Biological: CH505TF; Biological: CH505w53; Biological: CH505w78

Interventions

CH505TF BIOLOGICAL

Administered by intramuscular (IM) injection in the thigh

Also known as: CH505TF gp120

Part A: Group 1; Part A: Group 2; Part A: Group 3; Part B: Group 5; Part B: Group 6; Part C: Group 9

CH505w53 BIOLOGICAL

Administered by IM injection in the thigh

Also known as: CH505w53 gp120

Part B: Group 5; Part B: Group 6; Part C: Group 9

CH505w78 BIOLOGICAL

Administered by IM injection in the thigh

Also known as: CH505w78 gp120

Part B: Group 5; Part B: Group 6; Part C: Group 9

CH505 M5 BIOLOGICAL

Administered by IM injection in the thigh

Also known as: CH505 M5 gp120

Part B: Group 7

GLA-SE adjuvant BIOLOGICAL

Admixed with all CH505 gp120 proteins

Part A: Group 1; Part A: Group 2; Part A: Group 3; Part B: Group 5; Part B: Group 6; Part B: Group 7

Placebo BIOLOGICAL

Administered by IM injection in the thigh

Part A: Group 4; Part B: Group 8

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 through 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
• Agrees not to enroll in another study of an investigational research agent before the last required protocol clinic visit
• Willing to be contacted by phone, text message, or e-mail 6 months after completion of the scheduled clinic visits
• 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.
• Hemogram/Complete Blood Count (CBC):
• Hemoglobin greater than or equal to 11.5 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
• 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 115 study
• Pregnant or breastfeeding
• Active duty and reserve U.S. 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 115 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 115 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 for vaccines that have subsequently undergone licensure by the FDA or by the national regulatory authority where the volunteer is enrolling. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 115 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 115 PSRT on a case-by-case basis.
• Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever; live attenuated influenza vaccine)
• Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., 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 (8)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS

San Francisco, California, 94102, United States

Location

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

Boston, Massachusetts, 02115-6110, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• 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

Interventions

glucopyranosyl lipid-A

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

• Magda Sobieszczyk

  Columbia University

  STUDY CHAIR

• James Kobie

  University of Alabama at Birmingham

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 18, 2017
• Study Start: August 22, 2017
• Primary Completion: March 21, 2023
• Study Completion: March 21, 2023
• Last Updated: May 4, 2026
• Results First Posted: February 1, 2023

Record last verified: 2026-02

Locations

US (8)