A Clinical Trial to Look at the Safety and Immune Responses of the RNA-based Vaccine BNT168 in Adults Living With or Without HIV

A Randomized, Placebo-controlled, Phase I/II Clinical Trial to Evaluate the Safety, Immunogenicity, and Impact on Virological Control of the Investigational RNA-based Vaccine BNT168 in Adults Living With or Without HIV

This study will test a new ribonucleic acid (RNA)-based vaccine called BNT168 in adults living both with and without human immunodeficiency virus (HIV), to see how safe it is, how well it triggers the body's immune response and how it affects the amount of virus in the body.

Study Overview

• Status: Recruiting
• Conditions: HIV -1 Infection
• Intervention / Treatment: Biological: BNT168; Other: Placebo

Detailed Description

Currently, this study consists of one part (Part A) which will be a Phase I, randomized, placebo-controlled, double-blind, first-in-human (FIH), dose escalation with an initial proof-of-principle component. Depending on the safety and immunogenicity data generated in this study, the Phase II part of this study and/or some of the cohorts may not be initiated or may be terminated earlier by sponsor decision. In this study:

• Three cohorts of people living without HIV (PLWOH) will be randomized in a 5:1 ratio to receive BNT168 or placebo. Participants in these cohorts will receive 3 injections. BNT168 will be evaluated for safety, reactogenicity, and vaccine-induced immunogenicity in this population.
• Two cohorts of people living with HIV (PLWH), will be randomized in a 2:1 ratio to receive BNT168 or placebo. Participants in these cohorts will receive 4 injections. BNT168 will be evaluated in PLWH on combination antiretroviral therapy (cART) for safety, reactogenicity, and vaccine-induced immunogenicity in this population. An initial proof-of-principle assessment will be conducted in PLWH who undergo analytical treatment interruption (ATI) to evaluate viral kinetics after investigational medicinal product (IMP) administration. After the ATI period, cART will be restarted as per protocol.

For PLWOH, there will be an ~1-month screening period, ~2-month treatment period and an ~6-month follow-up period. The planned study duration per participant is ~9 months.

For PLWH, there will be an ~1-month screening period, ~6-month treatment period and an ~6-month follow-up period. The planned study duration per participant is maximum ~13 months.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77098
      • Recruiting
      • The Crofoot Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• Are 18 to 50 years of age inclusive at the time of giving informed consent.
• For PLWOH: Individuals who are HIV-1 and HIV-2 negative at Visit 0. For PLWH: Individuals who are HIV-1 positive and HIV-2 negative at Visit 0.
• Have not received an HIV vaccination or HIV broadly neutralizing antibody in another clinical study.
• Are overall healthy as defined in the protocol.
• Individuals who have screening hematology and/or blood chemistry laboratory values as defined in the protocol.

• For PLWOH, starting at Visit 0 and continuously until the last planned visit in this study, 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 infection risk reduction counseling.

• For PLWH, individuals who:

  • Have been on stable continuous cART for at least 12 months (defined as no interruptions longer than 14 continuous days) and with no changes in the components of the cART for at least 12 weeks prior to Visit 1.
  • Are not on a non-nucleoside reverse transcriptase inhibitor at screening.
  • Have never received lenacapavir and have not received other long-acting antiretroviral therapies in the last 2 years (i.e., intramuscular cabotegravir, cabotegravir-rilpivirine).
  • Are willing to undergo HIV transmission risk reduction counseling and to maintain low-risk behavior to protect their partners.
  • Have a CD4+ T cell count of ≥500 cells/µL at Visit 0.
  • Per medical history, any available prior CD4+ T cell count must be ≥350 cells/µL.
  • Have plasma HIV-1 RNA levels of <50 cps/mL for ≥6 months prior to study entry per investigator review of records and/or participant history (single measurements of <200 cps/mL are allowed if preceded and followed by values of <50 cps/mL).
  • Are willing to stop cART and undergo ATI at the timepoint defined in the protocol.
  • Are willing to re-initiate cART upon meeting cART restart criteria.
  • Site investigator anticipates that a fully active alternative cART regimen could be constructed and would be available in the event of virologic failure on the participant's current cART regimen.
• Agree not to donate blood from the time of first IMP administration until 90 days after the last IMP administration for PLWOH and until the End of Study Visit for PLWH.

Key Exclusion Criteria:

• Have had major surgery (e.g., major cardiopulmonary or abdominal operations) as per the investigator's judgment within 4 weeks before Visit 0, or will not have fully recovered from surgery, or have major surgery planned during the time the participants are expected to participate in the study.
• Have an abnormal electrocardiogram at Visit 0 as specified in the protocol.
• Have any existing condition which may affect IMP injection and/or assessment of local reactions, e.g., tattoos, severe scars, etc.
• Have any bleeding diathesis or condition associated with prolonged bleeding that, in the opinion of the investigator, could compromise their wellbeing if they participate in the study.
• Have any current febrile illness (body temperature >38.0°C/>100.4°F) or other acute illness within 48 hours prior to IMP administration
• Have any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, or any clinically significant cardiac disease per the investigator's judgment.
• Have Grade ≥2 hypertension per Food and Drug Administration toxicity grading scale at screening.
• Have a known or suspected impairment/alteration of immune function, autoimmune disease, or immunodeficiency (except HIV for PLWH), including receipt of any immunostimulant, immunomodulator, immunosuppressive medication, immunoglobulin, or blood/plasma product within 60 days prior to Visit 1 or planned administration during the study. Use of inhaled, intranasal, topical, or locally injected corticosteroids (e.g., intraarticular or intrabursal administration) is acceptable.
• 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 per protocol is exclusionary regardless of perceived risk of recurrence.
• Have received any live vaccines within 28 days prior to Visit 0 or any other vaccines within 14 days prior to Visit 0 or who are planning to receive any vaccine within 28 days of each IMP dose. When possible, standard of care vaccinations should be planned with the study interventions in mind.
• For PLWH: Have a history of opportunistic infections and/or AIDS-defining illnesses according to the US Centers for Disease Control and Prevention 2014 and the National Institutes of Health 2024.
• For PLWOH: Have current untreated or incompletely treated active tuberculosis infection (by history or concerning symptoms). For PLWH: Have current untreated or incompletely treated active tuberculosis infection (by history or concerning symptoms or sputum molecular testing) or current latent tuberculosis infection (by blood interferon-gamma release assay [IGRA]). Not excluded: Participants who have a positive IGRA but were fully treated for latent or active tuberculosis infection, per history, review of available records, and per investigator discretion.
• For PLWH: Have untreated or incompletely treated syphilis or genital, oropharyngeal or rectal gonorrhea or chlamydia infection.
• For PLWH: Have a history of multi-class drug resistant HIV-1 infection defined as resistance to three or more classes of HIV drugs.
• Have an estimated glomerular filtration rate of <45 mL/min/1.73 m2 using the 2021 chronic kidney disease epidemiology creatinine equation.
• History of any serious adverse reactions (including anaphylaxis, respiratory distress, angioedema, or urticaria) to vaccines or to vaccine components such as lipids.
• Have a history of progressive or severe neurologic disorder, seizure disorder, or Guillain-Barré syndrome.
• Have a history of diabetes mellitus type 1 or type 2, a screening hemoglobin A1c ≥6.5%, or are taking any medication for treatment of diabetes. (Not excluded: A history of isolated gestational diabetes.)

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1 in PLWOH - BNT168 dose level 1	Biological: BNT168; Intramuscular injection to be applied in the deltoid muscle, using the same non-dominant arm for all IMP injections
Experimental: A2 in PLWOH - BNT168 dose level 2	Biological: BNT168; Intramuscular injection to be applied in the deltoid muscle, using the same non-dominant arm for all IMP injections
Experimental: A3 in PLWOH - BNT168 dose level 3	Biological: BNT168; Intramuscular injection to be applied in the deltoid muscle, using the same non-dominant arm for all IMP injections
Experimental: A4 in PLWH - BNT168 dose level 2; This cohort will undergo ATI post vaccination	Biological: BNT168; Intramuscular injection to be applied in the deltoid muscle, using the same non-dominant arm for all IMP injections
Experimental: A5 in PLWH - BNT168 dose level 3; This cohort will undergo ATI post vaccination	Biological: BNT168; Intramuscular injection to be applied in the deltoid muscle, using the same non-dominant arm for all IMP injections
Placebo Comparator: PLWOH - Placebo	Other: Placebo; Isotonic sodium chloride (NaCl) solution (0.9%). Intramuscular injection to be applied in the deltoid muscle, using the same non-dominant arm for all IMP injections
Placebo Comparator: PLWH - Placebo; PLWH participants receiving placebo will also undergo ATI post vaccination	Other: Placebo; Isotonic sodium chloride (NaCl) solution (0.9%). Intramuscular injection to be applied in the deltoid muscle, using the same non-dominant arm for all IMP injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of at least one adverse event	In PLWOH and PLWH. By cohort and pooled placebo.	From dosing through 28 days after each IMP dose
Occurrence of at least one serious adverse event	In PLWOH and PLWH. By cohort and pooled placebo.	From Dose 1 through the end of study (up to 12 months)
Occurrence of at least one adverse event of special interest	In PLWOH and PLWH. By cohort and pooled placebo.	From Dose 1 through the end of study (up to 12 months)
Occurrence of at least one solicited local reaction (pain, erythema/redness, swelling) at the IMP injection site	In PLWOH and PLWH. By cohort and pooled placebo. From dosing through 7 days after each IMP dose.	Up to 7 days after each IMP dose
Occurrence of at least one solicited systemic event (vomiting, diarrhea, headache, fatigue/tiredness, myalgia/muscle pain, fever)	In PLWOH and PLWH. By cohort and pooled placebo. From dosing through 7 days after each IMP dose.	Up to 7 days after each IMP dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of cytokine positive cluster of differentiation (CD) 4+ T cells	In PLWOH and PLWH. By cohort and pooled placebo. For PLWOH, at 7 days post-Dose 2, and 7 days post-Dose 3. For PLWH, at 7 days post-Dose 2, 7 days post-Dose 3 and/or 7 days post-Dose 4. As assessed by multi-parameter intracellular cytokine staining (ICS) following stimulation with IMP-specific peptide pools.	Up to 7 days post-Dose 2, 3 and/or 4
Occurrence of cytokine positive CD8+ T cells	In PLWOH and PLWH. By cohort and pooled placebo. For PLWOH, at 7 days post-Dose 2 and 7 days post-Dose 3. For PLWH, at 7 days post-Dose 2, 7 days post-Dose 3 and/or 7 days post-Dose 4. As assessed by multi-parameter ICS following stimulation with IMP-specific peptide pools.	Up to 7 days post-Dose 2, 3 and/or 4
Occurrence of proliferating CD8+ T cell responses (measured by carboxifluorescein diacetate succinimidyl ester)	In PLWOH and PLWH. By cohort and pooled placebo. For PLWOH, at 28 days post-Dose 2 and 28 days post-Dose 3. For PLWH, at 28 days post-Dose 2, 28 days post-Dose 3 and 28 days post-Dose 4. As assessed by flow cytometry following stimulation with IMP-specific peptide pools.	At 28 days post-Dose 2, 3 and/or 4
Magnitude of CD4+ T cell counts from ATI start through cART restart	In PLWH. By cohort and pooled placebo.	Up to 168 days post ATI start
Change in CD4+ T cell count from ATI start to cART restart and end of study	In PLWH. By cohort and pooled placebo.	Up to 168 days post ATI start
Occurrence of absolute CD4+ T cell count <350 cells/µL from ATI start through cART restart	In PLWH. By cohort and pooled placebo.	Up to 168 days post ATI start
Occurrence of at least one adverse event from the start of ATI to cART restart	In PLWH. By cohort and pooled placebo.	Up to 168 days post ATI start
Occurrence of at least one serious adverse event from the start of ATI to cART restart	In PLWH. By cohort and pooled placebo.	Up to 168 days post ATI start
Occurrence of any acquired immunodeficiency syndrome (AIDS)-defining illness or opportunistic infection from the start of ATI to cART restart	In PLWH. By cohort and pooled placebo. AIDS-defining illnesses and opportunistic infections as listed in the protocol.	Up to 168 days post ATI start
Time from ATI start to loss of virologic control (HIV-1 plasma viral load >200 copies [cps]/mL, confirmed by the next measurement)	In PLWH. By cohort and pooled placebo.	Up to 168 days post ATI start
Time from ATI start to meeting cART restart criteria	In PLWH. By cohort and pooled placebo.	Up to 168 days post ATI start

Collaborators and Investigators

• Sponsor: BioNTech SE
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Acquired immunodeficiency syndrome (AIDS); HIV (human immunodeficiency virus); combination antiretroviral therapy (cART); Ribonucleic acid (RNA)-based vaccine
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: BNT168-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No