A Clinical Trial in Adult Participants Without HIV and in Overall Good Health to Evaluate the Safety and Immunogenicity of CD4BS CH505M5 Pr-NP1 Followed by CH505 TF chTrimer Boost Both Adjuvanted With Either Lipid Nanoparticles (LNPs) or 3M-052-AF + Alum

NCT06267872 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: HVTN 309
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a multicenter, open-label, phase 1 clinical trial to test two human immunodeficiency virus (HIV) vaccines with two adjuvants. An adjuvant is an ingredient used with some vaccines that may help people make an immune response. HIV is the virus that causes acquired immunodeficiency syndrome (AIDS). About 42 people will take part in the HVTN 309 clinical trial. This clinical trial will take place at multiple sites in the US and South Africa and the clinical trial is divided into 3 parts: Part A, Part B and Part C. About 3 people will participate in Part A of this study. After results from Part A are reviewed, it will be determined whether or not Part B and Part C of the clinical trial will proceed.

Conditions

HIV

Outcome Measures

Primary Outcomes (9)

• Frequency of local reactogenicity signs and symptoms after receipt of any study vaccine

  Part A: Day 15, 71, and 127; Part B: Day 15, 71, 127, 183, and 239; Part C: 15, 71, 127, 183, and 239 (14 days following receipt of any study vaccine)

• Frequency of systemic reactogenicity signs and symptoms after receipt of any study vaccine

  Part A: Day 15, 71, and 127; Part B: Day 15, 71, 127, 183, and 239; Part C: 15, 71, 127, 183, and 239 (14 days following receipt of any study vaccine)

• Number of serious adverse events (SAEs) leading to early participant withdrawal or permanent discontinuation

  31 months

• Number of medically attended adverse events (MAAEs) leading to early participant withdrawal or permanent discontinuation

  31 months

• Number of adverse events of special interest (AESIs) leading to early participant withdrawal or permanent discontinuation

  31 months

• Number of adverse events (AEs) leading to early participant withdrawal or permanent discontinuation

  31 months

• Part C only: Frequency of the CD4BS and CH505M5, G458Y, GNT1-specific, N280D KO IgG+ memory B cells, as assessed by flow cytometry

  Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)

• Part C only: Response rate of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains as measured by TZM-bl assay

  Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)

• Part C only: Magnitude of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains as measured by TZM-bl assay

  Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)

Secondary Outcomes (11)

• Parts B and C: Response rate of serum IgG binding Abs to autologous and heterologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)

  Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)

• Parts B and C: Magnitude of serum IgG binding Abs to autologous and heterologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)

  Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)

• Part B only: Response rate of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains as measured by the TZM-bl assay

  Part B: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)

• Part B only: Magnitude of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains as measured by the TZM-bl assay

  Part B: Day 127 and 239 (2 weeks after the third and fifth vaccinations respectively)

• Parts B and C: Response rate of differential serum Ab neutralization of precursor detection virus and corresponding epitope KO virus, as measured by TZM-bl assay

  Part B: Day 127 and 239; Part C: Day 127 and 239 (2 weeks after the third and fifth vaccinations, respectively, in each part)

Study Arms (7)

Part A - Group 1

EXPERIMENTAL

• 60 mcg of CD4BS CH505M5 Pr-NP1, to be administered as two 0.5 mL doses intramuscularly at months 0, 2, and 4.

Biological: CD4BS CH505M5 Pr-NP1

Part B - Group 2

EXPERIMENTAL

* 60 mcg of CD4BS CH505M5 Pr-NP1, admixed with 1.0 mg of ACU-026-001-1 adjuvant to be administered as two 0.5 mL doses intramuscularly at months 0, 2, and 4 * Followed by 300 mcg of CH505TF chTrimer, admixed with 1.0 mcg of ACU-026-001-1 adjuvant to be administered at months 6 and 8.

Biological: CD4BS CH505M5 Pr-NP1; Biological: CH505TF chTrimer; Biological: ACU-026-001-1 (labeled as empty LNP)

Part B - Group 3

EXPERIMENTAL

* 60 mcg of CD4BS CH505M5 Pr-NP1, admixed with 2.0 mg of ACU-026-001-1 adjuvant to be administered as two 0.5 mL doses intramuscularly at months 0, 2, and 4 * Followed by 300 mcg of CH505TF chTrimer, admixed with 2.0 mg of ACU-026-001-1 adjuvant to be administered at months 6 and 8.

Biological: CD4BS CH505M5 Pr-NP1; Biological: CH505TF chTrimer; Biological: ACU-026-001-1 (labeled as empty LNP)

Part B - Group 4

EXPERIMENTAL

* 60 mcg of CD4BS CH505M5 Pr-NP1, admixed with 5 mcg of 3M-052-AF adjuvant along with 500 mcg of Alum to be administered as two 0.5 mL doses intramuscularly at months 0, 2, and 4 * Followed by 300 mcg of CH505TF chTrimer, admixed with 5 mcg of 3M-052-AF adjuvant along with 500 mcg of Alum to be administered to be administered at months 6 and 8.

Biological: CD4BS CH505M5 Pr-NP1; Biological: CH505TF chTrimer; Biological: 3M-052-AF (labeled as AP 60-702); Biological: Aluminum Hydroxide Suspension (Alum)

Part C - Group 5

EXPERIMENTAL

Low dose: * 100 mcg of CD4BS CH505M5 Pr-NP1, admixed with 1.0 mg of ACU-026-001-1 adjuvant to be administered as two 0.5 mL doses intramuscularly at months 0, 2, and 4, * Followed by 300 mcg of CH505TF chTrimer, admixed with 1mg empty LNP adjuvant to be administered at months 6 and 8. OR, High Dose: * 100 mcg of CD4BS CH505M5 Pr-NP1, admixed with 2.0 mg of ACU-026-001-01 adjuvant to be administered as two 0.5 mL doses intramuscularly at month 0, 2, and 4, * Followed by 300 mcg of CH505TF chTrimer, admixed with 2.0 mg of ACU-026-001-1 adjuvant to be administered at months 6 and 8.

Biological: CD4BS CH505M5 Pr-NP1; Biological: CH505TF chTrimer; Biological: ACU-026-001-1 (labeled as empty LNP)

Part C - Group 6

EXPERIMENTAL

* 100 mcg of CD4BS CH505M5 Pr-NP1, admixed with 3 mcg of 3M-052-AF adjuvant along with 500 mcg of Alum to be administered as two 0.5 mL doses intramuscularly at months 0, 2, and 4, * Followed by 300 mcg of CH505TF chTrimer, admixed with 3 mcg of 3M-052-AF adjuvant along with 500 mcg of Alum to be administered to be administered at months 6 and 8.

Biological: CD4BS CH505M5 Pr-NP1; Biological: CH505TF chTrimer; Biological: 3M-052-AF (labeled as AP 60-702); Biological: Aluminum Hydroxide Suspension (Alum)

Part C - Group 7

EXPERIMENTAL

* 100 mcg of CD4BS CH505M5 Pr-NP1, admixed with 5 mcg of 3M-052-AF adjuvant along with 500 mcg of Alum to be administered as two 0.5 mL doses intramuscularly at months 0, 2, and 4 * Followed by 300 mcg of CH505TF chTrimer, admixed with 5 mcg of 3M-052-AF adjuvant along with 500 mcg of Alum to be administered to be administered at months 6 and 8.

Biological: CD4BS CH505M5 Pr-NP1; Biological: CH505TF chTrimer; Biological: 3M-052-AF (labeled as AP 60-702); Biological: Aluminum Hydroxide Suspension (Alum)

Interventions

CD4BS CH505M5 Pr-NP1 BIOLOGICAL

A ferritin NP expressing 8 copies of an HIV-1 Env protein trimer. To be administered intramuscularly (IM).

Part A - Group 1; Part B - Group 2; Part B - Group 3; Part B - Group 4; Part C - Group 5; Part C - Group 6; Part C - Group 7

CH505TF chTrimer BIOLOGICAL

A stabilized chimeric SOSIP Env trimer protein with the N-terminal sequence of CH505 TF gp120 Env transplanted into the BG505 SOSIP sequence. To be administered IM.

Part B - Group 2; Part B - Group 3; Part B - Group 4; Part C - Group 5; Part C - Group 6; Part C - Group 7

3M-052-AF (labeled as AP 60-702) BIOLOGICAL

An aqueous formulation (AF) of the small molecule imidazoquinoline immune response modifier (IRM) 3M-052; toll-like receptor (TLR)7/8 agonist.

Part B - Group 4; Part C - Group 6; Part C - Group 7

Aluminum Hydroxide Suspension (Alum) BIOLOGICAL

Alum to be administered IM as 500 mcg (aluminum content) admixed with 3M-052-AF (5 mcg) along with CD4BS CH505M5 Pr-NP1 and CH505 TF chTrimer.

Also known as: Alhydrogel

Part B - Group 4; Part C - Group 6; Part C - Group 7

ACU-026-001-1 (labeled as empty LNP) BIOLOGICAL

An AF consisting of 4 lipid components.

Part B - Group 2; Part B - Group 3; Part C - Group 5

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 (AoU): Volunteer demonstrates an understanding of this study and completes a questionnaire prior to signing the informed consent form(s) with verbal demonstration of understanding of questionnaire items that were answered incorrectly.
• to 55 years old, inclusive, on day of enrollment.
• Available for clinic follow-up through the last clinic visit, willing to undergo FNA and leukapheresis (for Part C only), and willing to be contacted 12 months after the last study-product administration.
• Agrees not to enroll in another study of an investigational agent during participation in the trial. If a potential participant is already enrolled in another clinical trial, approvals from the other trial sponsor and the HVTN 309 PSRT are required prior to enrollment into HVTN 309.
• In good general health according to the clinical judgment 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 by clinical staff as having a low likelihood of acquiring HIV per guidelines and agrees to discuss their potential for HIV acquisition, agrees to risk-reduction counseling, and agrees to avoid behaviors associated with a higher likelihood of acquiring HIV through the final study visit. Low likelihood may include persons stably taking pre-exposure prophylaxis (PrEP).
• Hemoglobin (Hgb):
• ≥ 11.0 g/dL for AFAB volunteers
• ≥ 13.0 g/dL for cisgender AMAB volunteers and for transgender men who have been on hormone therapy for more than 6 consecutive months
• ≥ 12.0 g/dL for transgender women who have been on hormone therapy for more than 6 consecutive months
• For transgender volunteers who have been on hormone therapy for less than 6 consecutive months, determine Hgb eligibility based on their sex assigned at birth.
• Platelets = 125,000 to 550,000/mm3.
• ALT \< 2.5 x upper limit of normal (ULN) based on the institutional normal range.
• Serum creatinine ≤ 1.1 x ULN based on the institutional normal range.

You may not qualify if:

• Volunteer who is breastfeeding or pregnant.
• Body mass index (BMI) ≥ 40. Enrollment of individuals with BMI ≥ 40, whom the site investigator assesses are in good health, may be considered by PSRT approval.
• Previous or current recipient of an investigational HIV vaccine (previous placebo/ control recipients are not excluded).
• Receipt of non-HIV experimental vaccine(s) received within the last 1 year. Exceptions include vaccines that have subsequently undergone licensure or Emergency Use Authorization (EUA) by the FDA or World Health Organization (WHO) Emergency Use Listing (EUL), or if outside the US, by the national regulatory authority (RA) authorizing this clinical trial.
• Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator, such as glucocorticoid use, equal to or greater than prednisone 10 mg/day within 3 months prior to enrollment.
• Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
• History of myocarditis and/or pericarditis.
• Receipt of any vaccine within 4 weeks prior to enrollment.
• 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 of greater than 7 days (or unknown half-life) within the past year, PSRT approval is required for enrollment.
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.
• Bleeding disorder diagnosed by a clinician which would make study procedures a contraindication.
• Asplenia or functional asplenia.
• Active duty and reserve US military personnel.
• Any other chronic or clinically significant condition that, in the clinical judgment of the investigator, would jeopardize the safety or rights of the study participant, including but not limited to: clinically significant forms of substance use or alcohol use disorder(s), serious psychiatric disorders, persons with any suicide attempt within the past 1 year (if between 1 and 2 years, consult PSRT for approval), or cancer that, in the clinical judgement of the site investigator, has potential for recurrence (excluding basal cell carcinoma).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health (NIH): collaborator
• Department of Health and Human Services: collaborator
• Duke University: collaborator
• Access to Advanced Health Institute (AAHI): collaborator

Study Sites (6)

Alabama CRS (Site ID: 31788)

Birmingham, Alabama, 35222, United States

Location

The Ponce de Leon Center CRS (Site ID: 5802)

Atlanta, Georgia, 30308, United States

Location

Vanderbilt Vaccine (VV) CRS (Site ID: 30352)

Nashville, Tennessee, 37232, United States

Location

Setshaba Research Centre CRS (Site ID: 31829)

Soshanguve, Gauteng, 0152, South Africa

Location

Isipingo CRS (Site ID: 31635)

Isipingo, KwaZulu-Natal, 4110, South Africa

Location

Klerksdorp CRS (Site ID: 30325)

Klerksdorp, North West, 2571, South Africa

Location

MeSH Terms

Interventions

Product Labeling; aluminum sulfate; Aluminum Hydroxide

Intervention Hierarchy (Ancestors)

Product Packaging; Industry; Technology, Industry, and Agriculture; Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes

Study Design

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

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 20, 2024
• Study Start: October 7, 2024
• Primary Completion: December 30, 2025
• Study Completion (Estimated): September 12, 2026
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (3); US (3)