A Clinical Trial Investigating the Safety and Biological Activity of the Antibody BNT351 in Adults Living Without and With HIV

Official title

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

Overview

This study will test the safety and blood levels of the antibody BNT351 in people living without and with human immunodeficiency virus (HIV). This study will also test the anti-viral activity of BNT351 in people living with HIV (PLWH) with detectable virus levels. The main goals of this study are: * To learn about the safety of BNT351 and check for side effects. * To measure the amount of BNT351 antibody in blood over time. * To test the amount of HIV in the blood at different times after treatment with BNT351 in people living with HIV.

Detailed description

The study will consist of two parts (Parts A and B).

Part A will be a randomized, double-blind, placebo-controlled, single ascending dose, first-in-human study part. Part A will enroll people living without HIV (PLWOH). Four cohorts are planned in Part A (Cohorts A1, A2, A3, and A4). Cohort A1 will evaluate one dose of BNT351 administered subcutaneously (SC). Cohorts A2 to A4 will evaluate three different doses of BNT351 administered intravenously (IV). For each cohort, participants will be randomized to BNT351 or placebo.

Part B will be single-dose, open-label, proof-of concept study part. Part B will enroll PLWH. Part B comprises two cohorts (Cohorts B1 and B2) and will be non-randomized.

Parts A and B will use a sentinel participant/staggered dosing approach in which dosing will start with a lower dose of BNT351 and then progress to the next dose level.

The study will start with recruitment into Part A. Depending on the available safety, pharmacokinetics, and/or viral kinetics data generated within this study, any of the Part A or B cohorts may not be initiated or may be terminated earlier by sponsor decision.

In Part A, for each participant, there will be an \~4-week screening period, one dose of BNT351 or placebo, and an \~38-week follow-up period. In total, Part A will last up to \~42 weeks per participant.

In Part B, for each participant, there will be an \~4-week screening period, one dose of BNT351, and an up to 8-week observation period with HIV viral load assessments, after which combination antiretroviral therapy (cART) will be started. Overall, participants will be followed for \~38 weeks after IMP administration and in total, Part B will last up to \~42 weeks per participant.

Interventions

• Drug BNT351
  IV infusion
• Drug Placebo
  IV infusion
• Drug BNT351
  SC injection
• Drug Placebo
  SC injection

Primary outcome measures

• Parts A and B - Occurrence of at least one adverse event (AE) [Time frame: From dosing to 56 days post-dose]
• Parts A and B - Occurrence of at least one serious AE (SAE) [Time frame: From dosing to 56 days post-dose]
• Parts A and B (except for Cohort A1) - Occurrence of infusion-related reactions (IRRs) Grade ≥2 (graded based on National Cancer Institute Common Terminology Criteria for AEs [NCI CTCAE] version 5.0 as specified in the protocol) [Time frame: From the start of IV dosing through 72 hours after the start of IV dosing]
• Parts A and B - Occurrence of at least one solicited local reaction (pain/tenderness, erythema/redness, induration/swelling) at the investigational medicinal product administration site [Time frame: From dosing through 7 days post-dose]
• Parts A and B- Occurrence of at least one solicited systemic event (vomiting, diarrhea, headache, fatigue/malaise, myalgia/arthralgia, fever) [Time frame: From dosing through 7 days post-dose]
• Parts A and B - Assessment of maximum concentration of BNT351 [Time frame: From dosing through 7 days post-dose]
• Part B - Occurrence of any acquired immunodeficiency syndrome (AIDS)-defining illness or opportunistic infection as defined in the protocol [Time frame: From dosing up to the time of cART initiation (up to a maximum of 56 days post-dose)]
• Part B - Occurrence of absolute CD4+ T cell count <350 cells/µL or CD4+ T cell count <15% of total lymphocyte count [Time frame: From dosing up to the time of cART initiation (up to a maximum of 56 days post-dose)]
• Part B - Change from baseline in HIV log10 plasma viral load prior to cART initiation [Time frame: At 7, 14, 21, 28, 35, 42, 49, and 56 days post-dose]
• Part B - Maximum decrease from baseline in HIV log10 plasma viral load prior to cART initiation [Time frame: From baseline up to the time of cART initiation (up to a maximum of 56 days post-dose)]

Secondary outcome measures (5)

• Parts A and B - Occurrence of at least one serious adverse event (SAE) [Time frame: From dosing through end of study (up to a maximum of 279 days post-dose)]
• Parts A and B - Assessment of area under the concentration-time curve of BNT351, from pre-dose to last quantifiable timepoint (AUClast) [Time frame: From pre-dose to last quantifiable timepoint (up to a maximum of 279 days post-dose)]
• Parts A and B - Incidence of detectable BNT351 anti-drug antibodies in serum [Time frame: From baseline until the end of study (up to a maximum of 279 days post-dose)]
• Part B - Magnitude of cluster of differentiation 4 positive (CD4+) T cell counts [Time frame: At dosing, 28 and 56 days post-dose or at time of cART initiation (up to a maximum of 56 days post-dose)]
• Parts B - Change from baseline in CD4+ T cell count [Time frame: At 28 days post-dose and at time of cART initiation (up to a maximum of 56 days post-dose)]

Eligibility criteria

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:

• 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.
• Agree to discuss HIV disease risks;
• 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:

• 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.
• 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.
• Have never received lenacapavir or ibalizumab or fostemsavir, and have not received other long-acting ARTs in the last 6 months (i.e., intramuscular cabotegravir, cabotegravir-rilpivirine).
• Have a CD4+ T cell count of ≥500 cells/µL and plasma HIV-1 RNA levels between 5,000-100,000 copies/mL at screening.
• 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).
• Are willing to undergo HIV transmission risk reduction counseling and to maintain low-risk behavior to protect their partners.

Exclusion criteria

Parts A and B:

• 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 (except for HIV infection, applicable to Part B only), 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 only:

• 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.

NOTE: Other protocol defined inclusion/exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 4 centers

• Cook County Health — Chicago
• Johns Hopkins — Baltimore
• Washington University — St Louis
• Columbia University — New York

Germany · 2 centers

• UK Köln — Cologne
• CRS Mannheim — Mannheim

Publications

• Kratochvil S, Kullmann M, Gruell H, Sayettat S, Tsai CH, Vukovic N, Janaitis C, Lindemann C, Prassl S, Stumpf R, Knufer J, Tolksdorf F, Sahin U, Nelke J, Malz A, Schommers P, Bhebhe S, Mkhize N, Moore P, Seaman MS, Klein F, Le Douce V. Preclinical assessment of broadly neutralizing HIV-1 antibody BNT351 with optimized pharmacokinetics and potent antiviral activity. iScience. 2026 Jun 11;29(6):1160 PMID 42325270

Identifiers

NCT: NCT07392372 · BNT351-01 · 2025-523846-29-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗