Safety and blood activity of the antibody BNT351 in adults with and without HIV

A Phase I First-in-human Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Antiviral Activity of the Broadly Neutralizing Antibody BNT351 in Adults Living Without and With HIV

This study will test whether one dose of the antibody BNT351 is safe, how long it stays in the blood, and if it lowers HIV levels in adults with and without HIV.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 61 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: BioNTech SE (Industry-sponsored)
• Drugs / interventions: cART
• Locations: 3 sites (Baltimore, Maryland and 2 other locations)
• Trial ID: NCT07392372 on ClinicalTrials.gov

What this trial studies

The study has two parts: Part A is a randomized, double-blind, placebo-controlled, single ascending dose first-in-human evaluation in adults without HIV, and Part B is an open-label, single-dose proof-of-concept cohort enrolling adults living with HIV. Part A includes four cohorts testing one subcutaneous dose and three intravenous doses with randomization to BNT351 or placebo and about 38 weeks of follow-up after dosing. Part B will enroll people with recent HIV diagnosis or who have recently stopped ART to receive a single dose of BNT351 and undergo up to 8 weeks of viral load monitoring before restarting combination antiretroviral therapy, with longer safety follow-up. Progression to Part B depends on review of safety data from Part A.

Who should consider this trial

Good fit: Ideal candidates are adults who are either HIV-negative and at low risk of acquiring HIV and willing to follow risk-reduction guidance (Part A) or adults living with HIV who are cART-naïve or recently diagnosed/recently off ART as specified in the protocol (Part B).

Not a fit: People on stable suppressive antiretroviral therapy with undetectable viral loads or those unwilling/unable to attend the multi-week follow-up visits are unlikely to gain measurable antiviral benefit from this study.

Why it matters

Potential benefit: If successful, BNT351 could become a new antibody option that safely reduces HIV levels and complements existing antiretroviral treatments.

How similar studies have performed: Previous studies of broadly neutralizing anti-HIV antibodies have produced transient reductions in viral load, so the approach has precedent, but BNT351 is a novel first-in-human antibody.

Eligibility criteria

Key Inclusion Criteria

Part A:

* Are HIV-1 and HIV-2 negative at Visit 0.
* Starting at Visit 0 and continuously until the last planned visit in this study are individuals who:

  1. Are assessed by the investigator as having a low likelihood of acquiring HIV and are committed to avoiding behaviors associated with a higher likelihood of acquiring HIV until the End of Study Visit.
  2. Agree to discuss HIV disease risks;
  3. Agree to HIV acquisition risk reduction counseling;

Part B:

* Are HIV-1 positive and HIV-2 negative at Visit 0.
* Individuals who at Visit 0:

  1. Are cART-naïve individuals who were diagnosed with HIV-1 infection ≤12 months prior to screening, OR are individuals who have discontinued cART and who were diagnosed with HIV-1 infection ≤12 months prior to screening or ≤18 months if this is found to be acceptable after discussion on a case-by-case basis with the sponsor's medical monitor.
  2. If cART-experienced, have discontinued cART for at least 4 weeks before screening (if the individual was taking long-acting antiretroviral therapy \[ART\]), see the following bullet). For individuals who have discontinued cART: Are able to comply with study procedures and assessments in the investigator's judgment.
  3. Have never received lenacapavir and have not received other long-acting ARTs in the last 6 months (i.e., intramuscular cabotegravir, cabotegravir-rilpivirine).
  4. Have a CD4+ T cell count of ≥400 cells/µL and plasma HIV-1 RNA levels between 1,000-100,000 copies/mL at screening.
  5. Are willing to initiate cART at a protocol-defined timepoint (56 days post-dose, or earlier if meeting early cART start criteria or at investigator's discretion).
  6. Are willing to undergo HIV transmission risk reduction counseling and to maintain low-risk behavior to protect their partners.

Key Exclusion Criteria:

Part A:

* Have received an HIV vaccination or HIV broadly neutralizing antibody in another clinical study.
* Have a known or suspected impairment/alteration of immune function or immunodeficiency, including receipt of any immunostimulant, immunomodulator, immunosuppressive medication, immunoglobulin, blood product, or oral or parenteral steroid within 60 days prior to Day 1 or planned administration during the study. The following exception applies: Use of inhaled, intranasal, topical, or locally injected corticosteroids (e.g., intraarticular or intrabursal administration) is allowed.
* Have a history of generalized urticaria or angioedema, or of allergy, anaphylaxis, hypersensitivity or intolerance to a human or humanized antibody or to BNT351 excipients.

Part B:

* Have received an HIV vaccination or HIV broadly neutralizing antibody in another clinical study.
* Are receiving ongoing therapy for Mycobacterium tuberculosis infection.
* Have a history of opportunistic infections/AIDS-defining illnesses as defined in the protocol.
* Have a history of multi-class drug resistant HIV-1 infection defined as resistance to three or more classes of HIV drugs.
* Have a history of malignancy within 5 years before screening. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or a malignancy which is considered in the investigator's judgment to have minimal risk of recurrence. Any malignancy that is an AIDS-defining illness (as defined in the protocol) is exclusionary regardless of the perceived risk of recurrence.
* Have a known or suspected impairment/alteration of immune function or immunodeficiency (except for HIV infection), including receipt of any immunostimulant, immunomodulator, immunosuppressive medication, immunoglobulin, blood product, or oral or parenteral steroid within 60 days prior to Day 1 or planned administration during the study. The following exception applies: Use of inhaled, intranasal, topical, or locally injected corticosteroids (e.g., intraarticular or intrabursal administration) is allowed.
* Have a history of generalized urticaria or angioedema, or of allergy, anaphylaxis, hypersensitivity or intolerance to a human or humanized antibody or to BNT351 excipients

NOTE: Other protocol defined inclusion/exclusion criteria may apply.

Where this trial is running

Baltimore, Maryland and 2 other locations

• Johns Hopkins — Baltimore, Maryland, United States (Recruiting)
• UK Köln — Cologne, Germany (Not_yet_recruiting)
• CRS Mannheim — Mannheim, Germany (Recruiting)

Study contacts

• Study coordinator: BioNTech clinical trials patient information

Conditions HIV -1 Infection; HIV-1; Treatment of HIV-1 infection; Antibody