Evaluating the Safety and Immunogenicity of ALVAC-HIV and MF59®- or AS01B-adjuvanted Bivalent Subtype C gp120 in Healthy, HIV-uninfected Adult Participants

NCT03122223 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 12036128
• Study Type: interventional
• Target: 160
• Locations: 4 countries
• Sites: 12

Brief Summary

A phase 1/2a clinical trial to evaluate the safety and immunogenicity of ALVAC-HIV (vCP2438) and of MF59®- or AS01B-adjuvanted clade C Env protein, in healthy, HIV-uninfected adult participants

Conditions

HIV Infections

Keywords

HIV

Outcome Measures

Primary Outcomes (12)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms During the Vaccine Regimen

  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 7 days after participants' last vaccination at Month 0,1,3, and 6

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms During the Primary Vaccine Regimen

  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 7 days after each vaccination at Month 0, 1, 3, and 6

• Frequency of Adverse Events by Relationship to the Study Product

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

  Measured through 30 days after each vaccination at Month 0, 1, 3 and 6.

• Frequency of SAEs, AESIs, and New Chronic Conditions

  No SAEs, AESIs, or new chronic conditions were reported over the course of the study

  Measured through Month 18.

• Alkaline Phosphatase, AST, ALT in U/L

  Laboratory results are summarized by analyte and timepoint.

  Measured at Month 0 (Screening) ,0.5(Day 14), 1.5 (Day 42) , 3.5 (Day 98) and 6.5 (Day 182)

• Hemoglobin, Creatinine in g/dL

  Laboratory results are summarized by analyte and timepoint.

  Measured at Month 0 (Screening) ,0.5(Day 14), 1.5 (Day 42) , 3.5 (Day 98) and 6.5 (Day 182)

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

  Laboratory results are summarized by analyte and timepoint.

  Measured at Month 0 (Screening) ,0.5(Day 14), 1.5 (Day 42) , 3.5 (Day 98) and 6.5 (Day 182)

• AEs or Reactro Leading to Early Participant Withdrawal or Early Discontinuation of Study Products Administration Throughout the Study.

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

  Measured through month 12

• Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine, After the Primary Vaccine Regimen. Measured by Flow Cytometry.

  PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing IL-2/IFNy after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. A response is positive if p\<=0.00001.The number and percentage of participants with positive responses are summarized by peptide pool.

  Measured at Month 6.5

• Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine, After the Primary Vaccine Regimen. Measured by Flow Cytometry.

  Measured by flow cytometry ICS assay: refer to earlier description for assay methods and analysis variable derivation. The percentage of T-cells expressing IL-1/IFNy are summarized for positive responders only.

  Measured at Month 6.5

• Number of Participants With HIV-specific Total IgG Binding Antibody (Vaccine gp120 Panel) Response Magnitude as Assessed by Binding Antibody Multiplex Assay [Time Frame: Measured at Month 12.]

  Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. 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. Values outside the linear range of the assay are not meaningful and are truncated: 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) net MFI \>= an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), and (2) net MFI \> 3 times baseline net MFI, and (3) experimental antigen MFI \> 3 times baseline MFI.

  Measured at Month 12

• Level of the HIV-specific Total IgG Binding Antibody (Vaccine gp120 Panel) Response Magnitude as Assessed by Binding Antibody Multiplex Assay [Time Frame: Measured at Month 12.]

  Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. 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. Values outside the linear range of the assay are not meaningful and are truncated: 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.

  Measured at Month 12

Secondary Outcomes (9)

• Occurrence of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine, After the Primary Vaccine Regimen. Measured by Flow Cytometry.

  Measured at Month 12

• Level of CD4+ T Cell Responses to the HIV Proteins Included in the Vaccine, After the Primary Vaccine Regimen. Measured by Flow Cytometry.

  Measured at Month 12

• Number of Participants With HIV-specific Total IgG Binding Antibody (Vaccine gp120 Panel) Response Magnitude as Assessed by Binding Antibody Multiplex Assay [Time Frame: Measured at Month 6.5.]

  Measured at Month 6.5

• Level of the HIV-specific Total IgG Binding Antibody (Vaccine gp120 Panel) Response Magnitude as Assessed by Binding Antibody Multiplex Assay [Time Frame: Measured at Month 6.5]

  Measured at Month 6.5

• Area Under Titration Curve of the HIV-specific Total IgG Binding Antibody (Vaccine gp120 Panel) Response Breadth as Assessed by Binding Antibody Multiplex Assay [Time Frame: Measured at Month 6.5.]

  Measured at Month 6.5

Study Arms (4)

ALVAC-HIV + 100mcg Protein/MF59 + Placebo

ACTIVE COMPARATOR

50 participants will receive 1 mL ALVAC-HIV injection in the left deltoid on Months 0, 1, 3, and 6. They will receive 0.5 mL100 mcg Protein/MF59 and 0.75 mL placebo injection in the right deltoid on Months 3 and 6.

Biological: ALVAC-HIV (vCP2438); Biological: Bivalent subtype C gp120/MF59; Biological: Placebo

ALVAC-HIV + 100mcg Protein/AS01(B) + Placebo

ACTIVE COMPARATOR

50 participants will receive 1 mL ALVAC-HIV injection in the left deltoid on Months 0, 1, 3, and 6. They will receive 0.75 mL100 mcg Protein/AS01(B) and 0.5 mL placebo injection in the right deltoid on Months 3 and 6.

Biological: ALVAC-HIV (vCP2438); Biological: Bivalent subtype C gp120/AS01(B); Biological: Placebo

ALVAC-HIV + 20mcg Protein/AS01(B) + Placebo

ACTIVE COMPARATOR

50 participants will receive 1 mL ALVAC-HIV injection in the left deltoid on Months 0, 1, 3, and 6. They will receive 0.75 mL 20 mcg Protein/AS01(B) and 0.5 mL placebo injection in the right deltoid on Months 3 and 6.

Biological: ALVAC-HIV (vCP2438); Biological: Bivalent subtype C gp120/AS01(B); Biological: Placebo

Placebo

PLACEBO COMPARATOR

10 participants will receive 1 mL of the placebo injection in the left deltoid on Months 0, 1, 3, and 6. They will receive 0.5 mL of the placebo injection and 0.75 mL of a separate placebo injection in the right deltoid on Months 3 and 6.

Biological: Placebo

Interventions

ALVAC-HIV (vCP2438) BIOLOGICAL

expresses the gene products 96ZM651 gp120 (clade C strain) linked to the sequences encoding the HIV-1 transmembrane anchor (TM) sequence of gp41 (28 amino acids clade B LAI strain) and Gag and Pro (clade B LAI strain). It is formulated as a lyophilized vaccine for injection at a viral titer greater than or equal to 1 × 10\^6 cell culture infectious dose (CCID)50 and less than 1 × 10\^8 CCID50 (nominal dose of 10\^7 CCID50) and is reconstituted with 1 mL of sterile sodium chloride solution (NaCl 0.4%), administered IM as a single 1 mL dose.

ALVAC-HIV + 100mcg Protein/AS01(B) + Placebo; ALVAC-HIV + 100mcg Protein/MF59 + Placebo; ALVAC-HIV + 20mcg Protein/AS01(B) + Placebo

Bivalent subtype C gp120/MF59 BIOLOGICAL

clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 100 mcg, mixed with MF59 adjuvant, administered IM as a single 0.5 mL dose.

ALVAC-HIV + 100mcg Protein/MF59 + Placebo

Bivalent subtype C gp120/AS01(B) BIOLOGICAL

clade C TV1.C gp120 Env and clade C 1086.C gp120 Env, each at a dose of 20 mcg or 100 mcg, mixed with AS01B adjuvant, administered IM as a single 0.75 mL dose.

ALVAC-HIV + 100mcg Protein/AS01(B) + Placebo; ALVAC-HIV + 20mcg Protein/AS01(B) + Placebo

Placebo BIOLOGICAL

Sodium Chloride for Injection, 0.9%, administered IM.

ALVAC-HIV + 100mcg Protein/AS01(B) + Placebo; ALVAC-HIV + 100mcg Protein/MF59 + Placebo; ALVAC-HIV + 20mcg Protein/AS01(B) + Placebo; Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria:
• Age of 18 to 40 years
• Access to a participating 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; provides answers to 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 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 the study protocol for more information about low risk guidelines).
• 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
• Total lymphocyte count greater than or equal to 800 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: 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 120 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 120 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 120 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. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 120 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) more than 5 years ago, eligibility for enrollment will be determined by the HVTN 120 PSRT on a case-by-case basis.
• Live attenuated vaccines received within 30 days before first study vaccination or scheduled within 14 days after first study vaccination (eg, 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 study vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)
• Allergy treatment with antigen injections within 30 days before first study vaccination or that are scheduled within 14 days after first study vaccination
• Immune System:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• GlaxoSmithKline: collaborator
• Sanofi Pasteur, a Sanofi Company: collaborator

Study Sites (12)

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

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

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

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS

Mbeya, Tanzania

Location

Matero Reference Clinic CRS

Lusaka, 10101, Zambia

Location

Seke South CRS

Chitungwiza, Zimbabwe

Location

Related Publications (2)

• 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

• Chirenje ZM, Laher F, Dintwe O, Muyoyeta M, deCamp AC, He Z, Grunenberg N, Laher Omar F, Seaton KE, Polakowski L, Woodward Davis AS, Maganga L, Baden LR, Mayer K, Kalams S, Keefer M, Edupuganti S, Rodriguez B, Frank I, Scott H, Stranix-Chibanda L, Gurunathan S, Koutsoukos M, Van Der Meeren O, DiazGranados CA, Paez C, Andersen-Nissen E, Kublin J, Corey L, Ferrari G, Tomaras G, McElrath MJ. Protein Dose-Sparing Effect of AS01B Adjuvant in a Randomized Preventive HIV Vaccine Trial of ALVAC-HIV (vCP2438) and Adjuvanted Bivalent Subtype C gp120. J Infect Dis. 2024 Aug 16;230(2):e405-e415. doi: 10.1093/infdis/jiad434.

  PMID: 37795976 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

AIDSVAX

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 Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Z Mike Chirenje

  UZ-UCSF Collaborative Research Program

  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: February 14, 2017
• First Posted: April 20, 2017
• Study Start: January 16, 2018
• Primary Completion: July 30, 2020
• Study Completion: July 30, 2020
• Last Updated: March 14, 2023
• Results First Posted: January 8, 2021

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ZI (1); TA (1); US (9); ZA (1)