Evaluating the Safety and Immunogenicity of Polyvalent DNA/gp120 HIV Vaccine in Healthy, HIV-uninfected Adults

NCT04927585 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: WHV138
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the safety, tolerability, and immunogenicity of polyvalent env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein vaccines (PDPHV201401) co-administered together with or without adjuvant in repeated doses in healthy, HIV-uninfected adults

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (7)

• Frequency of local injection site (including DTH) reactogenicity signs and symptoms

  Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

  Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in

• Frequency of systemic reactogenicity signs and symptoms

  Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

  Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in

• Frequency of adverse events (AEs)

  AEs categorized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class, MedDRA preferred term, severity, and assessed relationship to study products

  Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in

• Severity of local injection site (including DTH) reactogenicity signs and symptoms

  Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

  Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in

• Severity of systemic reactogenicity signs and symptoms

  Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

  Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in

• Severity of adverse events (AEs)

  AEs categorized by MedDRA system organ class, MedDRA preferred term, severity, and assessed relationship to study products

  Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in

• Number of participants with early discontinuation of vaccinations

  Tabulated by reason and treatment arm

  Measured through participants' last study visit, at Month 20 to 24, depending on which part of the study participants are enrolled in

Secondary Outcomes (4)

• Magnitude of serum HIV-1 Env-specific IgG responses

  Measured at 2 weeks after the last vaccination

• Serum neutralizing antibody responses against Tier 1A, Tier 1B, and selected Tier 2 viruses

  Measured at 2 weeks after the last vaccination

• Breadth of gp70-V1V2 IgG and gp120 IgA

  Measured at 2 weeks after the last vaccination

• Frequency of HIV-1 specific CD4+ and CD8+ T-cell responses

  Measured at 2 weeks after the last vaccination

Study Arms (4)

Group 1 (Treatment): DNA Vaccine + Protein Vaccine/GLA-SE

EXPERIMENTAL

Participants will receive 2 mg of env (A,B,C,A/E)/gag (C) DNA vaccine and 400 mcg of gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant at Day 0, and Months 3, 6, and 12.

Biological: env (A,B,C,A/E)/gag (C) DNA Vaccine; Biological: gp120 (A,B,C,A/E) Protein Vaccine; Biological: GLA-SE adjuvant

Group 1 (Control)

PLACEBO COMPARATOR

Participants will receive placebo at Day 0, Months 3, 6, and 12. Interventions:

Biological: Placebo

Group 2 (Treatment): Admixture of DNA Vaccine and Protein Vaccine

EXPERIMENTAL

Participants will receive admixture of 2 mg of env (A,B,C,A/E)/gag (C) DNA vaccine and 400 mcg of gp120 (A,B,C,A/E) protein vaccine (no adjuvant) at Day 0, and Months 1, 3, 6, and 8.

Biological: env (A,B,C,A/E)/gag (C) DNA Vaccine; Biological: gp120 (A,B,C,A/E) Protein Vaccine

Group 2 (Control)

PLACEBO COMPARATOR

Participants will receive placebo at Day 0, and Months 1, 3, 6, and 8. Interventions:

Biological: Placebo

Interventions

env (A,B,C,A/E)/gag (C) DNA Vaccine BIOLOGICAL

Administered by intramuscular injection in the deltoid

Also known as: Polyvalent DNA (PDPHV-201401) Plasmid

Group 1 (Treatment): DNA Vaccine + Protein Vaccine/GLA-SE; Group 2 (Treatment): Admixture of DNA Vaccine and Protein Vaccine

gp120 (A,B,C,A/E) Protein Vaccine BIOLOGICAL

Administered by intramuscular injection in the deltoid

Also known as: PDPHV-201401 Recombinant Proteins gp120A, gp120B, gp120C, gp120AE

Group 1 (Treatment): DNA Vaccine + Protein Vaccine/GLA-SE; Group 2 (Treatment): Admixture of DNA Vaccine and Protein Vaccine

GLA-SE adjuvant BIOLOGICAL

Administered by intramuscular injection in the deltoid.

Also known as: glucopyranosyl lipid adjuvant-stable emulsion

Group 1 (Treatment): DNA Vaccine + Protein Vaccine/GLA-SE

Placebo BIOLOGICAL

Sodium Chloride for Injection, USP 0.9%; Administered by intramuscular injection in the deltoid.

Group 1 (Control); Group 2 (Control)

Eligibility Criteria

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

You may qualify if:

• Age of 18 to 50 years
• Access to BWH trial site 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
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• 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. HVTN low risk guidelines will be used.
• Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 12.0 g/dL for volunteers who were born male
• White blood cell count = 3,000 to 12,000 cells/mm3
• Total lymphocyte count \> 800 cells/mm3
• Remaining differential either within institutional normal range or with site physician approval
• Platelets = 125,000 to 450,000/mm3 Chemistry
• Chemistry panel: ALT, AST, and alkaline phosphatase \< 1.25 times the institutional upper limit of normal; creatinine \< 1.1 times the institutional upper limit of normal.

You may not qualify if:

• Blood products received within 120 days before first vaccination
• Investigational research agents received within 30 days before first vaccination
• Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age \> 45, systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 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
• Pregnant or breastfeeding
• Active duty and reserve US military personnel Vaccines and other Injections
• HIV vaccine(s) received in a prior HIV vaccine trial.
• Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial, unless the vaccine subsequently received regulatory approval or emergency authorization.
• Live attenuated vaccines, other than influenza vaccine, 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
• Serious adverse reactions to vaccines or to vaccine components including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)
• Immunoglobulin received within 60 days before first vaccination
• Autoimmune disease, connective tissue disease, or history of vasculitis, eg, leukocytoclastic vasculitis, Henoch-Schonlein Purpura
• Immunodeficiency Clinically significant medical conditions

Sponsors & Collaborators

• Worcester HIV Vaccine: lead
• Brigham and Women's Hospital: collaborator
• Access to Advanced Health Institute (AAHI): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Genes, env; Vaccines, DNA; Plasmids; HIV Envelope Protein gp120; 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

Intervention Hierarchy (Ancestors)

Genes, Viral; Genes, Microbial; Genes; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Genome, Microbial; Genome, Viral; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; Antigens; Biological Factors; HIV Antigens; Antigens, Viral; Viral Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins

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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2021
• First Posted: June 16, 2021
• Study Start: July 8, 2021
• Primary Completion: December 7, 2023
• Study Completion: December 7, 2023
• Last Updated: April 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)