Evaluating the Safety and Immunogenicity of Stabilized CH505 TF chTrimer in Healthy, HIV-uninfected Adult Participants.

NCT04915768 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 30038705
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label Phase 1 study to examine the safety and immunogenicity of the CH505 TF chTrimer vaccine with 3M-052-AF +/- Alum adjuvant in healthy adults. The primary hypothesis is that the CH505 TF chTrimer will expand CH103-like B-cell precursors. HVTN 300 Part A examined the safety and immunogenicity of the CH505TF chTrimer with 5 mcg 3M-052-AF + 500 mcg Alum. HVTN 300 Part B was added to this protocol with a goal of assessing the optimal dosing and combination of 3M-052-AF and Alum adjuvant, that can potentially lead to improved neutralizing antibody activity and decreased reactogenicity, compared to Part A. Three groups were added to Part B (Group 2: 3 mcg 3M-052-AF without Alum, Group 3: 3 mcg 3M-052 with Alum, and Group 4: 5 mcg 3M-052-AF without Alum). HVTN 300 Part B is being added to this protocol with a goal of assessing the optimal dosing and combination of 3M-052-AF and Alum adjuvant, that can potentially lead to improved neutralizing antibody activity and decreased reactogenicity, compared to Part A. Three groups have been added to Part B (Group 2: 3 mcg 3M-052-AF without Alum, Group 3: 3 mcg 3M-052 with Alum, and Group 4: 5 mcg 3M-052-AF without Alum).

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (11)

• Number of Participants Reporting Local Reactogenicity Events Signs and Symptoms: Erythema and/or Induration

  The number and percentage of subjects experiencing each type of reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]

  Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)

• Number of Participants Reporting Local Reactogenicity Events Signs and Symptoms: Pain and/or Tenderness

  The number and percentage of subjects experiencing each type of reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]

  Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)

• Number of Participants Showing Systemic Vaccination Reactogenicity Signs and Symptoms

  The number and percentage of subjects experiencing each type of systemic reactogenicity sign or symptom was tabulated by severity. For a given symptom, reactogenicity per subject was counted once based on the maximum severity across all assessments. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]

  Measured through 7 days after each study product administration at Study Day 0 (Month 0), Day 56 (Month 2), Day 112 (Month 4), Day 224 (Month 8), and Day 364 (Month 12)

• Number of Participants Reporting Unsolicited Adverse Events (AEs) Tabulated by Maximum Severity Grade

  The number and percentage of subjects reporting adverse events was tabulated by severity. For a given participant with multiple adverse events reported, maximum severity was taken. 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). All unsolicited adverse events were collected for 30 days after any receipt of study vaccination. Serious adverse events (SAEs), medically attended adverse events (MAAEs), adverse events of special interest (AESIs) and AEs leading to early participant withdrawal or permanent discontinuation which were collected throughout the study and for twelve months following any receipt of study product

  All unsolicited adverse events were collected for 30 days after any receipt of study vaccination. Some adverse events (noted in description) were collected for 12 months following any receipt of study product (up to 104 weeks)

• Number of Participants Reporting Serious Adverse Events (SAEs)

  The number and percentage of subjects reporting servious adverse events (SAEs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]

  Serious adverse events (SAEs) were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)

• Number of Participants Reporting One or More Medically Attended Adverse Events (MAAEs)

  The number and percentage of subjects reporting medically attended adverse events (MAAEs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]

  Medically attended adverse events (MAAEs) were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)

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

  The number and percentage of subjects reporting adverse events of special interest (AESIs). Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]

  Adverse events of special interest (AESIs)were collected throughout the study and for 12 months following any receipt of study product (up to 104 weeks)

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

  From the vaccination and adverse event case report forms, counts are tabulated by treatment arm

  Measured through 12 months following any receipt of study product (up to 104 weeks

• Frequency of the CD4 Binding-site, V2 Apex and V3 Glycan (bnAb Region at the Base of the V3 Loop), and/or CH505TF-specific IgG+ B Cells

  Measured by flow cytometry analysis

  Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination

• Response Rate of Serum Antibody Neutralization of Vaccine-matched Tier 2 HIV-1 Strains

  Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. Response to an isolate was considered positive if the neutralization titer was above a pre-specified cutoff. The pre-specified positivity call was an ID50 (or ID80) value ≥ 10,

  Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination

• Magnitude of Serum Antibody Neutralization of Vaccine-matched Tier 2 HIV-1 Strains

  Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells.

  Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination

Secondary Outcomes (4)

• Response Rate of Serum IgG Binding Antibodies

  Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination

• Magnitude of Serum IgG Binding Antibodies

  Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination

• Response Rate of Serum Antibody Neutralization of Heterologous HIV-1 Strains

  Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination

• Magnitude of Serum Antibody Neutralization of Heterologous HIV-1 Strains

  Measured at baseline, 2 weeks post 3rd vaccination, 2 weeks post 4th vaccination and 2 weeks post 5th vaccination

Study Arms (4)

Group 1: Treatment

EXPERIMENTAL

CH505 TF chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF + (500 mcg) Aluminum Hydroxide suspension, administered at months 0, 2, 4, 8 and 12.

Biological: CH505 TF chTrimer; Biological: 3M-05-AF; Biological: Aluminum hydroxide suspension

Group 2: Treatment

EXPERIMENTAL

CH505 TF chTrimer 300 mcg admixed with (3 mcg) 3M-052-AF administered at months 0, 2, 4, 8 and 12.

Biological: 3M-05-AF; Biological: CH505 TF chTrimer

Group 3: Treatment

EXPERIMENTAL

CH505 cTrimer, 300 mcg admixed with (3 mcg) 3M-052-AF + (500 mcg) Aluminum Hydroxide suspension (Alum) administered at months 0, 2, 4, 8 and 12.\* \*On October 13, 2023, errors were identified in the study injection preparation for this Group. The instructions below state that the doses for injections in Group 3 should be 300 mcg of the study vaccine + 3 mcg of 3M-052-AF adjuvant + 500 mcg of Alum adjuvant. However, the step-by-step instructions below for preparing the injection result in 2.2 mcg of 3M-052-AF (instead of 3 mcg) and 556 mcg of Alum (instead of 500 mcg). Thus, Group 3 participants got less 3M-052-AF than intended and more Alum than intended.

Biological: CH505 TF chTrimer; Biological: 3M-05-AF; Biological: Aluminum hydroxide suspension

Group 4: Treatment

EXPERIMENTAL

CH505 chTrimer 300 mcg admixed with (5 mcg) 3M-052-AF administered at months 0, 2, 4, 8 and 12.

Biological: 3M-05-AF; Biological: CH505 TF chTrimer

Interventions

3M-05-AF BIOLOGICAL

Combined with CH505 TF chTrimer and Alum adjuvant. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle.

Group 1: Treatment; Group 3: Treatment

CH505 TF chTrimer BIOLOGICAL

Combined with adjuvants 3M-052-AF and Alum. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle.

Group 1: Treatment; Group 3: Treatment

Aluminum hydroxide suspension BIOLOGICAL

Combined with CH505 TF chTrimer and 3M-052-AF adjuvant. Combination administered as two 0.5 mL doses via intramuscular injection into deltoid muscle

Group 1: Treatment; Group 3: Treatment

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to complete the informed consent process, including an 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.
• years old, inclusive, on day of enrollment.
• Available for clinic follow-up through the last clinic visit, willing to undergo lymph node fine needle aspiration and leukapheresis, and willing to be contacted 12 months after the last vaccine administration.
• Agrees not to enroll in another study of an investigational agent during participation in the trial.
• In good general health according to the clinical judgement of the site investigator.
• Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgement of the site investigator.
• Assessed as low risk for HIV acquisition per low risk guidelines (see protocol for more information), agrees to discuss HIV infection risks, agrees to risk reduction counseling, and agrees to avoid behavior associated with high risk of HIV exposure through the final study visit. Low risk may include persons stably taking PrEP (pre- exposure prophylaxis) as prescribed for 6 months or longer.
• Hemoglobin \>12.5 mg/dL to 18 mg/dL
• White blood cell (WBC) count \> 3,500/mm³
• Platelets ≥125,000 /mm³
• Alanine aminotransferase (ALT) \< 2.5 x ULN based on the institutional normal range
• Serum creatinine ≤1.1 x ULN based on the institutional normal range
• Blood pressure in the range of 90 to \< 160 mmHg systolic and 50 to \< 100 mmHg diastolic.
• Negative results for HIV infection by an FDA-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).
• Negative for anti-Hepatitis C antibodies (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV antibodies are detected.

You may not qualify if:

• Volunteer who is breast-feeding or pregnant.
• Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
• Systemic glucocorticoid use equal to or greater than prednisone10 mg/day within 3 months prior to enrollment, congenital or acquired immunodeficiency or other systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator.
• Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
• Receipt of any live attenuated vaccine within 4 weeks prior to enrollment.
• Receipt of any vaccines that are not live attenuated within 14 days prior to enrollment; replication incompetent vaccines such as the Jynneos vaccine for the prevention of monkeypox disease are not considered to be live vaccines.
• ACAM2000 vaccine for Monkeypox received within 30 days prior to enrollment or receipt of study product, or if ACAM2000 received greater than 30 days prior to enrollment or receipt of study product, vaccination scab still present; or planned administration within 30 days after enrollment or receipt of study product.
• Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life greater than 7 days (or unknown half- life) within the past year, PSRT approval is required for enrollment.
• Serious reactions to vaccines that preclude receipt of study injections as determined by the principal investigator or designee. History of serious reaction (eg. hypersensitivity, anaphylaxis) to any vaccine or any component of the study vaccine, including imidazoquinolone (eg, imiquimod).
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.
• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
• Asplenia or functional asplenia.
• Active duty and reserve US military personnel.
• Any other chronic or clinically significant condition that in the clinical judgement of the investigator would jeopardize the safety or rights of the study participant, including, but not limited to: clinically significant forms of drug or alcohol abuse, serious psychiatric disorders, or cancer that, in the clinical judgement of the site investigator, has a potential for recurrence (excluding basal cell carcinoma).

Sponsors & Collaborators

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

Study Sites (3)

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

Brigham and Women's CRS

Boston, Massachusetts, 02115, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 30030, United States

Location

Related Publications (1)

• Walsh S, Hahn WO, Williams WB, Hyrien O, Yu PC, Parks KR, Edwards RJ, Parks R, Barr M, Polakowski LL, Tindale I, Jones M, Yurdadon C, Burnham R, Yeh CH, Heptinstall J, Seaton K, Andriesen J, Sagawa Z, Miner MD, De Rosa S, McElrath MJ, Corey L, Tomaras GD, Montefiori DC, Haynes BF, Mayer KH, Baden LR. Safety and immunogenicity of an HIV envelope trimer immunogen that elicits CD4 binding site neutralizing antibody precursors (HVTN 300). medRxiv [Preprint]. 2026 Apr 3:2026.03.31.26349761. doi: 10.64898/2026.03.31.26349761.

  PMID: 41959788 DERIVED

MeSH Terms

Conditions

HIV Infections

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: Jaessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Center

hvtn.covpn.sdmc@hvtn.org

206-667-5812

Study Officials

• Kenneth H Mayer, M.D.

  Beth Israel Deaconess Medical Center

  STUDY CHAIR

• Lindsey R Baden, M.D.

  Brigham and Women's Hospital

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 7, 2021
• Study Start: January 23, 2023
• Primary Completion: July 15, 2025
• Study Completion: July 15, 2025
• Last Updated: April 14, 2026
• Results First Posted: February 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)