Evaluating the Safety and Immunogenicity of Env (A,B,C,A/E)/Gag (C) DNA and gp120 (A,B,C,A/E) Protein/GLA-SE HIV Vaccines, Given Individually or Co-administered, in Healthy, HIV-1-Uninfected Adults

NCT03409276 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 12438302
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of env (A,B,C,A/E)/gag (C) DNA and gp120 (A,B,C,A/E) protein/GLA-SE HIV-1 vaccines (PDPHV-201401) as a prime-boost regimen or co-administered in repeated doses, in healthy, HIV-1-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (11)

• Number of 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, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 days after participants' each vaccination at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B

• 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, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 days after participants' each vaccination at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B

• Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product

  For participants reporting multiple AEs over the time frame, the maximum relationship is counted.

  Measured through 30 days after each vaccine dose at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B

• Number of Participants Reporting Adverse Events (AEs), by Severity Grade

  For participants reporting multiple AEs over the time frame, the maximum severity grade is counted.

  Measured through 30 days after each vaccine dose at Months 0, 2 for part A and Months 0, 1, 3, 6, 8 for part B

• Number of Participants Reporting Serious Adverse Events (SAEs)

  Measured as outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual).

  Measured through Month 8 for part A and Month 14 for part B

• Number of Participants Reporting Adverse Events of Special Interest (AESIs)

  Adverse events of special interest were described in Appendix N of the protocol. AESI for this protocol include but are not limited to potential immune-mediated diseases. There were no adverse events of special interest reported by any participant.

  Measured through Month 8 for part A and Month 14 for part B

• Numbers of Participants With Grade 1 or Higher Local Laboratory Results

  The number (percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria or above as specified in the DAIDS AE Grading Table were tabulated by treatment arm for each post-vaccination time point. 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, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B

• Alk Phos, AST, ALT in UL

  Laboratory results are summarized by analyte and timepoint.

  Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B

• Hemoglobin, Creatinine in g/dL

  Laboratory results are summarized by analyte and timepoint.

  Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B

• WBC, Platelets, Lymphocytes, Neutrophils in Thousand Cells/Cubic mm

  Laboratory results are summarized by analyte and timepoint.

  Measured through Screening, Day 14, Day 70, Day140 for part A and visits Screening, Day 14, Day 42, Day 98, Day 182, Day 238 and Day 334 for part B

• Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation

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

  Measured through study completion, up to 31 months

Secondary Outcomes (10)

• Occurrence of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination

  Measured at Month 2.5 for part A and 8.5 for part B

• Levels of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination

  Measured at Month 2.5 for part A and 8.5 for part B

• Breadth of IgG HIV-1 Env-specific IgG Responses Two Weeks After the Last Vaccination

  Measured at Month 2.5 for part A and 8.5 for part B

• Part B: Occurrence of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination

  Measured at Month 8.5 for part B only

• Part B: Levels of Serum Neutralizing Antibody Responses Against Tier 1A, Tier 1B, and Selected Tier 2 Viruses Two Weeks After the Last Vaccination

  Measured at Month 8.5 for part B only

Study Arms (6)

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

EXPERIMENTAL

Participants will receive 400 mcg of gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant at Day 0 and Month 2.

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 and Month 2.

Biological: Placebo

Group 2 (Treatment) DNA Vaccine+Placebo+Protein Vaccine/GLA-SE

EXPERIMENTAL

Participants will receive 2 mg of env (A,B,C,A/E)/gag (C) DNA vaccine and placebo at Day 0 and Months 1 and 3. Participants will receive 400 mcg of gp120 (A,B,C,A/E) protein vaccine admixed with GLA-SE adjuvant and a placebo vaccine at Months 6 and 8.

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

Group 2 (Control)

PLACEBO COMPARATOR

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

Biological: Placebo

Group 3 (Treatment): DNA Vaccine+Protein Vaccine/GLA-SE

EXPERIMENTAL

Participants will receive 2 mg of the 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 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; Biological: GLA-SE adjuvant

Group 3 (Control)

PLACEBO COMPARATOR

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

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 2 (Treatment) DNA Vaccine+Placebo+Protein Vaccine/GLA-SE; Group 3 (Treatment): DNA Vaccine+Protein Vaccine/GLA-SE

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): Protein Vaccine/GLA-SE; Group 2 (Treatment) DNA Vaccine+Placebo+Protein Vaccine/GLA-SE; Group 3 (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); Group 2 (Treatment) DNA Vaccine+Placebo+Protein Vaccine/GLA-SE; Group 3 (Control)

GLA-SE adjuvant BIOLOGICAL

Administered by intramuscular injection in the deltoid.

Also known as: glucopyranosyl lipid adjuvant-stable emulsion

Group 1 (Treatment): Protein Vaccine/GLA-SE; Group 2 (Treatment) DNA Vaccine+Placebo+Protein Vaccine/GLA-SE; Group 3 (Treatment): DNA Vaccine+Protein Vaccine/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 12 months after the last vaccination
• 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
• 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 11.0 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 124 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 124 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 124 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 124 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 124 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
• 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.)

Sponsors & Collaborators

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

Study Sites (6)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• Jamieson PJ, Shen X, Abu-Shmais AA, Wasdin PT, Janowska K, Edwards RJ, Scapellato G, Bukenya M, Bass LE, Richardson SI, Manamela NP, Liu S, Barr M, Adams L, Paola Velez-Castro C, McCarthy C, Alexander CA, Gillespie RA, Mimms J, Suryadevara N, Sornberger TA, Zost SJ, Parks R, Flaherty S, Janke AK, Howard BN, Suresh YP, Ruprecht RM, Crowe JE Jr, Carnahan RH, Bailey JR, Kanekiyo M, Lingwood D, Haynes BF, Moore PL, Bonami RH, Tomaras GD, Archarya P, Montefiori DC, Kalams SA, Lu S, Georgiev IS. Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity. J Virol. 2025 Dec 23;99(12):e0125625. doi: 10.1128/jvi.01256-25. Epub 2025 Nov 10.

  PMID: 41212034 DERIVED

• Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.

  PMID: 40190112 DERIVED

• Frank I, Li SS, Grunenberg N, Overton ET, Robinson ST, Zheng H, Seaton KE, Heptinstall JR, Allen MA, Mayer KH, Culver DA, Keefer MC, Edupuganti S, Pensiero MN, Mehra VL, De Rosa SC, Morris DE, Wang S, Seaman MS, Montefiori DC, Ferrari G, Tomaras GD, Kublin JG, Corey L, Lu S; HVTN 124 Study Team. Safety and immunogenicity of a polyvalent DNA-protein HIV vaccine with matched Env immunogens delivered as a prime-boost regimen or coadministered in HIV-uninfected adults in the USA (HVTN 124): a phase 1, placebo-controlled, double-blind randomised controlled trial. Lancet HIV. 2024 May;11(5):e285-e299. doi: 10.1016/S2352-3018(24)00036-5.

  PMID: 38692824 DERIVED

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

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

• Ian Frank

  University of Pennsylvania

  STUDY CHAIR

• Turner Overton

  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: January 9, 2018
• First Posted: January 24, 2018
• Study Start: March 16, 2018
• Primary Completion: May 11, 2020
• Study Completion: October 22, 2020
• Last Updated: April 25, 2022
• Results First Posted: April 25, 2022

Record last verified: 2022-03

Locations

US (6)