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

NCT07392372 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: BNT351-012025-523846-29-00
• Study Type: interventional
• Target: 67
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

HIV -1 Infection

Keywords

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

Outcome Measures

Primary Outcomes (12)

• Parts A and B - Occurrence of at least one adverse event (AE)

  Per part, by cohort/dose

  From dosing to 56 days post-dose

• Parts A and B - Occurrence of at least one serious AE (SAE)

  Per part, by cohort/dose

  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)

  Per part, by cohort/dose

  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

  Per part, by cohort/dose

  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)

  Per part, by cohort/dose

  From dosing through 7 days post-dose

• Parts A and B - Assessment of maximum concentration of BNT351

  Per part, by cohort/dose

  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

  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

  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

  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

  From baseline up to the time of cART initiation (up to a maximum of 56 days post-dose)

• Part B - Time from dosing to lowest viral load prior to cART initiation

  From dosing up to the time of cART initiation (up to a maximum of 56 days post-dose)

• Part B - Time from dosing to viral rebound defined as HIV-1 RNA viral load increase >0.75 log10 copies/mL from nadir (i.e., lowest HIV-1 RNA viral load from 7 days post-dose (Visit 3) and through pre-cART initiation)

  From dosing up to the time of cART initiation (up to a maximum of 56 days post-dose)

Secondary Outcomes (5)

• Parts A and B - Occurrence of at least one serious adverse event (SAE)

  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)

  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

  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

  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

  At 28 days post-dose and at time of cART initiation (up to a maximum of 56 days post-dose)

Study Arms (6)

Part A - Cohort A1

EXPERIMENTAL

PLWOH will be randomized to BNT351 (at a protocol defined dose level) or placebo (2:1)

Drug: BNT351; Drug: Placebo

Part A - Cohort A2

EXPERIMENTAL

PLWOH will be randomized to BNT351 (at a protocol defined dose level) or placebo (3:1)

Drug: BNT351; Drug: Placebo

Part A - Cohort A3

EXPERIMENTAL

PLWOH will be randomized to BNT351 (at a protocol defined dose level) or placebo (3:1)

Drug: BNT351; Drug: Placebo

Part A - Cohort A4

EXPERIMENTAL

PLWOH will be randomized to BNT351 (at a protocol defined dose level) or placebo (3:1)

Drug: BNT351; Drug: Placebo

Part B - Cohort B1

EXPERIMENTAL

PLWH will receive BNT351 at a protocol-defined dose level. cART will start 56 days post-BNT351 dosing or earlier.

Drug: BNT351

Part B - Cohort B2

EXPERIMENTAL

PLWH will receive BNT351 at a protocol-defined dose level. cART will start 56 days post-BNT351 dosing or earlier.

Drug: BNT351

Interventions

BNT351 DRUG

IV infusion

Part A - Cohort A2; Part A - Cohort A3; Part A - Cohort A4; Part B - Cohort B1; Part B - Cohort B2

Placebo DRUG

IV infusion

Part A - Cohort A2; Part A - Cohort A3; Part A - Cohort A4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (6)

Cook County Health

Chicago, Illinois, 60612, United States

NOT YET RECRUITING

Johns Hopkins

Baltimore, Maryland, 21205-1832, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

NOT YET RECRUITING

Columbia University

New York, New York, 10032, United States

NOT YET RECRUITING

UK Köln

Cologne, 50937, Germany

RECRUITING

CRS Mannheim

Mannheim, 68167, Germany

ACTIVE NOT RECRUITING

Related Publications (1)

• 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):116022. doi: 10.1016/j.isci.2026.116022. eCollection 2026 Jun 19.

  PMID: 42325270 DERIVED

Study Officials

• BioNTech Response Person

  BioNTech SE

  STUDY DIRECTOR

Central Study Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084; patients@biontech.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part B will be open-label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2026
• First Posted: February 6, 2026
• Study Start: February 9, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); DE (2)