A Clinical Trial to Evaluate the Safety, Efficacy and Immune Responses After Vaccination With an Investigational RNA-based Vaccine Against Malaria

NCT06069544 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BNT165-02
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 5

Brief Summary

This is a randomized, dose-escalation Phase I/IIa trial to evaluate safety, tolerability, immunogenicity and efficacy of an investigational RNA-based vaccine (BNT165e) for prevention of P. falciparum malaria in healthy malaria-naive adults. The multi-antigen malaria vaccine (designated BNT165e) is a combination of three distinct RNAs, BNT165c and BNT165d (composed of BNT165d1 and BNT165d2), encoding P. falciparum antigens encapsulated in lipid nanoparticles. The BNT165c RNA encodes the full Plasmodium falciparum circumsporozoite protein. The BNT165d1 and BNT165d2 RNAs both encode conserved, immunogenic segments of liver stage-expressed proteins.

Conditions

Malaria

Keywords

RNA vaccine; Vaccine; Active immunization against malaria; Plasmodium falciparum

Outcome Measures

Primary Outcomes (5)

• Frequency of solicited local reactions at the injection site (pain, erythema/redness, induration/swelling) recorded up to 7 days after each dose

  For each cohort in participants receiving at least one dose of trial intervention.

  Up to 7 days after each dose

• Frequency of solicited systemic reactions (vomiting, diarrhea, headache, fatigue, muscle/joint pain, and fever) recorded up to 7 d after each dose

  For each cohort in participants receiving at least one dose of trial intervention.

  Up to 7 days after each dose

• Frequency of participants with at least one adverse event occurring until 28 days after each dose

  For each cohort in participants receiving at least one dose of trial intervention.

  Up to 28 days after each dose

• Frequency of participants with at least one medically attended adverse event occurring until 24 weeks after last received IMP dose

  For each cohort in participants receiving at least one dose of trial intervention

  Up to 24 weeks after last received IMP dose

• Frequency of participants in each cohort with at least one serious adverse event occurring until 24 weeks after last received IMP dose

  For each cohort in participants receiving at least one dose of trial intervention.

  Up to 24 weeks after last received IMP dose

Secondary Outcomes (1)

• Descriptive statistics on antibody levels (including geometric means and 95% confidence interval) at assessed timepoints

  Up to 365 days after last received IMP dose

Study Arms (2)

BNT165e

EXPERIMENTAL

Escalating dose levels

Biological: BNT165e

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Placebo OTHER

Isotonic NaCl solution (0.9%)

Placebo

BNT165e BIOLOGICAL

Multi-antigen RNA-based vaccine for active immunization against malaria administered as intramuscular injection

BNT165e

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Have given informed consent by signing and dating the informed consent form (ICF) before initiation of any trial-specific procedures.
• Are willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions and other requirements of the trial. This includes that they are able to understand and follow trial-related instructions.
• Are aged 18 to 55 years, have a body mass index over 18.5 kg/m\^2 and under 35 kg/m\^2 and weigh at least 45 kg at Visit 0.
• Are healthy, in the clinical judgment of the investigator based on volunteer-reported medical history data, and physical examination, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory test outcomes at Visit 0.
• Note: Healthy volunteers with pre-existing stable disease (e.g., obesity, hypertension), defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 90 days before Visit 0, can be included.
• Agree not to enroll in another trial with an IMP starting from Visit 0 and until 12 weeks after receiving Dose 3.
• Have not traveled and agree not to travel to a malaria-endemic region, as defined per Centers for Disease Control and Prevention (CDC) (https://www.cdc.gov/malaria/travelers/country\_table/a.html) starting 6 months before Visit 0 and continuously until 28 days after receiving Dose 3.
• Negative human immunodeficiency virus -1 and -2 blood test result at Visit 0.
• Negative Hepatitis B surface antigen test result at Visit 0 and negative anti-Hepatitis C virus (anti-HCV) antibodies, or negative HCV polymerase chain reaction test result if the anti-HCV is positive at Visit 0.
• Volunteers of childbearing potential (VOCBP) that have a negative serum beta-human chorionic gonadotropin pregnancy test result at Visit 0 and negative urine pregnancy test results before each IMP administration. Volunteers born female who are postmenopausal or permanently sterilized will not be considered VOCBP.
• VOCBP who agree to practice a highly effective form of contraception starting at Visit 0 and continuously until 90 days after receiving Dose 3.
• VOCBP who agree not to donate or cryopreserve eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting at Visit 0 and continuously until 90 days after receiving Dose 3.
• Men who have not had a vasectomy and are sexually active with partners of childbearing potential and who agree to use condoms and to practice a highly effective form of contraception with their sexual partners of childbearing potential during the trial, starting at Visit 0 and continuously until 90 days after receiving Dose 3.
• Men who are willing to refrain from sperm donation, starting at Visit 0 and continuously until 90 days after receiving Dose 3.

You may not qualify if:

• History of Plasmodium parasitemia (any species) based on volunteer-reported medical history.
• Prior residence for ≥6 months continuously in a malaria-endemic region as defined per CDC (https://www.cdc.gov/malaria/travelers/country\_table/a.html) at any point during their lifetime.
• Breastfeeding or intending to become pregnant or to father children starting with Visit 0 and continuously until 90 days after receiving Dose 3.
• History of any serious adverse reactions to vaccines or to vaccine components such as lipids, and including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had an anaphylactic adverse reaction to pertussis vaccine as a child).
• Current or history of the following medical conditions:
• Uncontrolled or moderate or severe respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease); symptoms of asthma severity as defined in the US National Asthma Education and Prevention Program Expert Panel report, 2020 - e.g., exclude a volunteer who:
• Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or
• Uses high dose inhaled corticosteroids (per American Academy of Allergy Asthma and Immunology), or
• In the past year has either of the following:
• Greater than one exacerbation of symptoms treated with oral/parenteral corticosteroids
• Needed hospitalization, or intubation for asthma.
• History of Diabetes mellitus type 1 or type 2, including cases controlled with diet alone or elevated hemoglobin A1C ≥6.5% at screening (not excluded: history of isolated gestational diabetes).
• Hypertension:
• If a person has a history of hypertension, or elevated blood pressure detected during screening, exclude for blood pressure that is not well controlled. Well controlled blood pressure is defined as consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤150 mm Hg systolic and ≤100 mm Hg diastolic at screening and enrollment.
• Malignancy within 5 years of screening, excluding localized basal or squamous cell skin cancer.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (5)

AMR Tempe

Tempe, Arizona, 85281, United States

Location

University of Maryland, Center for Vaccine Development

Baltimore, Maryland, 21201, United States

Location

AMR Las Vegas

Las Vegas, Nevada, 89119, United States

Location

AMR Knoxville

Knoxville, Tennessee, 37909, United States

Location

Clinical Trials of Texas

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Mo AX, McGugan G, Pesce JT. Meeting report: Expert consultation on late arresting replication competent (LARC) malaria sporozoite vaccine research & development. Vaccine. 2025 Apr 30;54:127009. doi: 10.1016/j.vaccine.2025.127009. Epub 2025 Apr 16.

  PMID: 40245769 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Observer-blinded
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2023
• First Posted: October 6, 2023
• Study Start: November 13, 2023
• Primary Completion: May 28, 2025
• Study Completion: March 20, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)