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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
Accepted
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 or ibalizumab or fostemsavir, 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 ≥500 cells/µL and plasma HIV-1 RNA levels between 5,000-100,000 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:
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.
Primary outcome measure(s)
Parts A and B - Occurrence of at least one adverse event (AE) — From dosing to 56 days post-dose Per part, by cohort/dose
Parts A and B - Occurrence of at least one serious AE (SAE) — From dosing to 56 days post-dose Per part, by cohort/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) — From the start of IV dosing through 72 hours after the start of IV dosing Per part, by cohort/dose
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 — From dosing through 7 days post-dose Per part, by cohort/dose
Parts A and B- Occurrence of at least one solicited systemic event (vomiting, diarrhea, headache, fatigue/malaise, myalgia/arthralgia, fever) — From dosing through 7 days post-dose Per part, by cohort/dose
Parts A and B - Assessment of maximum concentration of BNT351 — From dosing through 7 days post-dose Per part, by cohort/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)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.