Evaluating Safety and Immune Response to the HIV-1 CH505 Transmitted/Founder gp120 Adjuvanted With GLA-SE in Healthy, HIV-exposed Uninfected Infants

NCT04607408 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 135UM1AI068614
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluated the safety and immune response in healthy HIV-exposed and uninfected infants to the protein vaccine, CH505TF gp120, adjuvanted with GLA-SE.

Conditions

HIV Infections

Keywords

HIV; Vaccine; Infant

Outcome Measures

Primary Outcomes (14)

• WHO Anthropometric Measure of Weight-for-Age Z-Score

  At each study visit, the infant's weight was measured. Using weight and age, a WHO weight-for-age z-score will be calculated using the World Health Organization (WHO) anthropometric calculator tool. Weight-for-age reflects body weight relative to the child's age on a given day. A Z-score of 0 represents the population mean, a Z-score less than -2 indicates an infant who is underweight, -2 to 2 indicates an infant who is normal weight, and above 2 indicates the infant may have a growth problem, but this is better assessed from weight-for-length. This Outcome Measure was not collected for Mothers.

  Measured at each study visit.

• Number (Percentage) of Participants by WHO Anthropometric Measure of Weight-for-Age Z-Score Categories

  At each study visit, the infant's weight was measured. Using weight and age, a WHO weight-for-age z-score was calculated using the World Health Organization (WHO) anthropometric calculator tool. Weight-for-age reflects body weight relative to the child's age on a given day. Z-scores less than -2 indicates an infant who is underweight, -2 to 2 indicates an infant who is normal weight, and above 2 indicates the infant may have a growth problem, but this is better assessed from weight-for-length.

  Measured at each study visit.

• WHO Anthropometric Measure of Weight-for-Length Z-Score

  At each study visit, the infant's length and weight was measured. Using these measurements, a WHO weight-for-length z-score was calculated using the World Health Organization (WHO) anthropometric calculator tool. Weight-for-length reflects body weight in proportion to attained growth in length. A Z-score of 0 represents the population mean, a Z-score less than -2 indicates an infant who is wasted, -2 to 2 indicates an infant who is normal weight, and above 2 indicates the infant is overweight. This Outcome Measure was not collected for Mothers.

  Measured at each study visit.

• Number (Percentage) of Participants by WHO Anthropometric Measure of Weight-for-Length Z-Score Categories

  At each study visit, the infant's length and weight was measured. Using these measurements, a WHO weight-for-length z-score was calculated using the World Health Organization (WHO) anthropometric calculator tool. Weight-for-length reflects body weight in proportion to attained growth in length. Z-scores less than -2 indicates an infant who is wasted, -2 to 2 indicates an infant who is normal weight, and above 2 indicates the infant is overweight.

  Measured at each study visit.

• 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. This Outcome Measure was not collected for Mothers.

  Measured through 7 days after each vaccine dose (Weeks 0, 8, 16, 32, 54).

• 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. This Outcome Measure was not collected for Mothers.

  Measured through 7 days after each vaccine dose (Weeks 0, 8, 16, 32, 54).

• 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 following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: fever, sleepiness/lethargy, rash, vomiting, anorexia, seizure. The item Max. Systemic Symptoms is the maximum of the individual systemic reactogenicities for a participant. This Outcome Measure was not collected for Mothers.

  Measured through 7 days after each vaccine dose (Weeks 0, 8, 16, 32, 54).

• Number (Percentage) of Participants With Local Laboratory Values Recorded as Meeting Grade 1 AE Criteria or Above as Specified in the Division of AIDS Table.

  The number (percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria or above as specified in the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events for alanine aminotransferase (ALT), creatinine, hemoglobin, lymphocyte count, neutrophil count, platelets, white blood cells (WBC) was summarized by treatment arm for each post vaccination time point. This Outcome Measure was not collected for Mothers.

  ALT, creatinine, hemoglobin, platelets, and WBC measured at Screening (Day 0) and Days 14, 70, 126, 238, 393, 743; Lymphocytes and Neutrophils measured at Days 14, 70, 126, 238, 393, 743.

• Number of Participants Reporting AEs, by Highest Severity Grade Per Participant.

  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 (exceptions apply). This Outcome Measure was not collected for Mothers.

  Comprises the entire study period for each infant participant (from the infant's study enrollment until his or her study completion or discontinuation), up to 25 months.

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

  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 (exceptions apply). This Outcome Measure was not collected for Mothers.

  Comprises the entire study period for each infant participant (from the infant's study enrollment until his or her study completion or discontinuation), up to 25 months.

• Number of Participants Reporting Serious Adverse Events (SAEs)

  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 (exceptions apply). This Outcome Measure was not collected for Mothers.

  Comprises the entire study period for each infant participant (from the infant's study enrollment until his or her study completion or discontinuation), up to 25 months.

• Magnitude of HIV-1 Env gp120, CD4 Binding Site and V1V2-specific Serum IgG Binding Antibodies, as Assessed by BAMA Two Weeks After the 5th Vaccination

  Serum HIV-1-specific IgG responses were measured on a BioPlex instrument (BioRad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control. Net MFI less than 1 is set to 1, and net MFI \> 22,000 is set to 22,000. The area under the curve (AUC) was calculated for each participant and antigen using the trapezoidal rule, where the x-axis is log10 dilution and the y-axis is the Net MFI with negative values set to 0. AUC is considered the primary measure of response magnitude.

  Measured at month 13, 2 weeks after the 5th vaccination.

• Quantification and Phenotypic Characterization of Peripheral B Cells Capable of Binding HIV-1 Env gp120 and the CD4 Binding Site, as Assessed by Flow Cytometry Two Weeks After the 3rd Vaccination

  HIV-1 Env-specific B cells induced by vaccination were identified and characterized using fluorescently labeled recombinant Env proteins in the context of a flow cytometry panel to identify and characterize those B cell. Total B cells are identified using doublet exclusion, lymphocyte scatter profile, a viability dye to exclude dead cells, and are negative for lineage markers: CD3, CD56 and CD14; and positive for CD19 and CD20. B cells are further gated as IgD-, then IgG+, and IgA+.

  Measured at month 4.5 (2 weeks post the 3rd vaccination).

• Quantification and Phenotypic Characterization of Peripheral B Cells Capable of Binding HIV-1 Env gp120 and the CD4 Binding Site, as Assessed by Flow Cytometry Two Weeks After the 5th Vaccinations

  HIV-1 Env-specific B cells induced by vaccination were identified and characterized using fluorescently labeled recombinant Env proteins in the context of a flow cytometry panel to identify and characterize those B cell. Total B cells are identified using doublet exclusion, lymphocyte scatter profile, a viability dye to exclude dead cells, and are negative for lineage markers: CD3, CD56 and CD14; and positive for CD19 and CD20. B cells are further gated as IgD-, then IgG+, and IgA+.

  Measured at month 13 (2 weeks after the 5th vaccination).

Secondary Outcomes (11)

• EPI Vaccine-specific Antibody Responses, as Assessed by Pediatric Vaccine Multiplex Assay (PVMA) 2 Weeks After the 5th Vaccination (Diptheria, HepB, Pertussis, Rubella, and Tetanus)

  Measured at month 13, 2 weeks after the 5th vaccination.

• EPI Vaccine-specific Antibody Responses, as Assessed by Pediatric Vaccine Multiplex Assay (PVMA) 2 Weeks After the 5th Vaccination (HiB and RSV)

  Measured at month 13, 2 weeks after the 5th vaccination.

• Magnitude and Breadth of Serum Neutralization of Vaccine-matched Viral Isolates, and Viruses Engineered to Detect Precursors of CD4 Binding Site and V1V2 Antibodies 2 Weeks After the 5th Vaccination.

  Measured at month 13, 2 weeks after the 5th vaccination.

• Response Rate of Vaccine-elicited Serum Binding Antibodies to FcR Proteins, as Assessed by BAMA 2 Weeks After the 5th Vaccination

  Measured at month 13, 2 weeks after the 5th vaccination.

• Magnitude of Vaccine-elicited Serum Binding Antibodies to FcR Proteins, as Assessed by BAMA 2 Weeks After the 5th Vaccination

  Measured at month 13, 2 weeks after the 5th vaccination.

Study Arms (8)

Part A, Group 1: CH505TF gp120 + GLA-SE

EXPERIMENTAL

Participants received 20 mcg Stable CH505TF gp120 admixed with 2.5 mcg GLA-SE, administered as a 0.25 mL intramuscular (IM) injection into either thigh at Weeks 0, 8, 16, 32, and 54.

Biological: CH505TF gp120; Biological: GLA-SE adjuvant

Part A, Group 2: Placebo

PLACEBO COMPARATOR

Participants received Placebo administered as a 0.25 mL IM injection, into either thigh at Weeks 0, 8, 16, 32, and 54.

Biological: Placebo

Part B, Group 3: CH505TF gp120 + GLA-SE

EXPERIMENTAL

Participants received 20 mcg Stable CH505TF gp120 admixed with 5 mcg GLA-SE, administered as a 0.5 mL IM injection into either thigh at Weeks 0, 8, 16, 32, and 54.

Biological: CH505TF gp120; Biological: GLA-SE adjuvant

Part B, Group 4: Placebo

PLACEBO COMPARATOR

Participants received Placebo administered as a 0.5 mL IM injection, into either thigh at Weeks 0, 8, 16, 32, and 54.

Biological: Placebo

Part C, Group 5: CH505TF gp120 + GLA-SE

EXPERIMENTAL

Participants received 20 mcg Stable CH505TF gp120 admixed with 5 mcg GLA-SE, administered as a 0.5 mL IM injection into either thigh at Weeks 0, 8, 16, 32, and 54.

Biological: CH505TF gp120; Biological: GLA-SE adjuvant

Part C, Group 6: Placebo

PLACEBO COMPARATOR

Participants received Placebo administered as a 0.5 mL IM injection, into either thigh at Weeks 0, 8, 16, 32, and 54.

Biological: Placebo

Part C, Group 7: CH505TF gp120 + GLA-SE

EXPERIMENTAL

Participants received 5 mcg Stable CH505TF gp120 admixed with 5 mcg GLA-SE, administered as a 0.5 mL IM injection into either thigh at Weeks 0, 8, 16, 32, and 54.

Biological: CH505TF gp120; Biological: GLA-SE adjuvant

Part C, Group 8: Placebo

PLACEBO COMPARATOR

Participants received Placebo administered as a 0.5 mL IM injection, into either thigh at Weeks 0, 8, 16, 32, and 54.

Biological: Placebo

Interventions

CH505TF gp120 BIOLOGICAL

HIV-1 CH505 transmitted/founder virus Env gp120 immunogen

Part A, Group 1: CH505TF gp120 + GLA-SE; Part B, Group 3: CH505TF gp120 + GLA-SE; Part C, Group 5: CH505TF gp120 + GLA-SE; Part C, Group 7: CH505TF gp120 + GLA-SE

GLA-SE adjuvant BIOLOGICAL

An oil-in-water stable emulsion (SE) containing the immunological adjuvant Glucopyranosyl Lipid A (GLA)

Part A, Group 1: CH505TF gp120 + GLA-SE; Part B, Group 3: CH505TF gp120 + GLA-SE; Part C, Group 5: CH505TF gp120 + GLA-SE; Part C, Group 7: CH505TF gp120 + GLA-SE

Placebo BIOLOGICAL

Sodium Chloride for Injection, 0.9% USP

Part A, Group 2: Placebo; Part B, Group 4: Placebo; Part C, Group 6: Placebo; Part C, Group 8: Placebo

Eligibility Criteria

• Age: 0 Days - 5 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may not qualify if:

• Estimated gestational age at birth is at least 37 weeks.
• Weight at birth is at least 2.5 kg.
• Has initiated antiretroviral prophylaxis consistent with current site-specific standard of care.
• Hemoglobin \>14.0 g/dL.
• White Blood Cell Count ≥ 7000 cells/mm3
• Platelets \> 100,000 cells/mm3
• Alanine aminotransferase (ALT) \<1.25 times upper limit of age adjusted normal.
• Creatinine \< 1.1 times upper limit of age adjusted normal.
• Negative HIV-1 nucleic acid test on specimen drawn within 72 hours of birth.
• Written informed consent provided by mother.
• Age is equal to or less than five days.
• Any clinically significant congenital anomaly/birth defect.
• Documented or suspected serious medical illness, infection, clinically significant finding from physical examination or immediate life-threatening condition, including requirement for ongoing supplemental oxygen, as judged by the examining clinician.
• Receipt of any other investigational product.
• Mother's age is at least 18 years, and willing and able to provide written informed consent for her and her infant's participation in this study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• HIV Vaccine Trials Network: lead

Study Sites (1)

Perinatal HIV Research Unit (PHRU), Soweto CRS

Johannesburg, Gauteng, 1862, South Africa

Location

Related Publications (2)

• Violari A, Otwombe K, Hahn W, Chen S, Josipovic D, Baba V, Angelidou A, Smolen KK, Levy O, Mkhize NN, Woodward Davis AS, Martin TM, Haynes BF, Williams WB, Sagawa ZK, Kublin JG, Polakowski L, Brewinski Isaacs M, Yen C, Tomaras G, Corey L, Janes H, Gray GE. Safety and implementation of phase I randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns. J Clin Invest. 2025 Apr 3;135(11):e186927. doi: 10.1172/JCI186927. eCollection 2025 Jun 2.

  PMID: 40178906 DERIVED

• Violari A, Otwombe K, Hahn W, Chen S, Josipovic D, Baba V, Angelidou A, Smolen KK, Levy O, Mkhize NN, Woodward AS, Martin TM, Haynes B, Williams WB, Sagawa ZK, Kublin J, Polakowski L, Isaacs MB, Yen C, Tomaras G, Corey L, Janes H, Gray G. Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns. medRxiv [Preprint]. 2024 Oct 17:2024.10.15.24315548. doi: 10.1101/2024.10.15.24315548.

  PMID: 39484284 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 Center

hvtn.covpn.sdmc@hvtn.org

2066675812

Study Officials

• Avy Violari

  Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital

  STUDY CHAIR

• Georgia Tomaras

  Duke University, HVTN Laboratory

  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: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: October 29, 2020
• Study Start: November 10, 2020
• Primary Completion: July 24, 2024
• Study Completion: July 24, 2024
• Last Updated: January 29, 2026
• Results First Posted: August 6, 2025

Record last verified: 2026-01

Locations

ZA (1)