Safety and Immune Responses After Vaccination With an Investigational RNA-based Vaccine Against Malaria

NCT05581641 | Completed Phase 1 Results FDA Drug

• 1 other identifier: BNT165-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

This first-in-human clinical trial, was a dose escalation multi-center trial designed to assess the safety, tolerability, and immunogenicity of the vaccine component, BNT165b1, a ribonucleic acid (RNA)-lipid nanoparticle (LNP) encoding for part of the Plasmodium falciparum circumsporozoite protein (PfCSP). BNT165b1 was evaluated at three dose levels (DLs) to select a safe and tolerable dose in a 3-dose schedule.

Conditions

Malaria

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Solicited Local Reactions

  A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) and pre-listed (that is, solicited) in the e-diary. Solicited local reactions included: pain at the injection site, erythema/redness, and induration/swelling. The intensity of AEs was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants may have been counted more than once if they reported multiple episodes of the event for the specified doses.

  Up to 7 days post any vaccination, and up to 7 days post each vaccination dose (i.e., post Dose 1 [at Day 8], Dose 2 [at Day 64] and Dose 3 [at Day 190])

• Number of Participants With Solicited Systemic Reactions

  A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the e-diary. Solicited systemic reactions included: vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, and fever. The intensity of AEs was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants may have been counted more than once if they reported multiple episodes of the event for the specified doses.

  Up to 7 days post any vaccination, and up to 7 days post each vaccination dose (i.e., post Dose 1 [at Day 8], Dose 2 [at Day 64] and Dose 3 [at Day 190])

• Number of Participants With Adverse Events (AEs)

  An AE was defined as any untoward medical occurrence in a participant administered with a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. The intensity of AEs was graded by the investigator. Grades were defined as: Grade 1 - Mild; does not interfere with the trial participant's usual function; Grade 2 - Moderate; interferes to some extent with the trial participant's usual function; Grade 3 - Severe; interferes significantly with the trial participant's usual function and Grade 4 - Potentially life-threatening; life-threatening consequences, urgent intervention required. Participants may have been counted more than once if they reported multiple episodes of the event for the different doses.

  Up to 28 days post any vaccination, and up to 28 days post each vaccination dose (i.e., post Dose 1 [at Day 29], Dose 2 [at Day 85] and Dose 3 [at Day 211])

• Number of Participants With Serious Adverse Events (SAEs)

  An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death and was life-threatening. It also included any event requiring hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, caused a congenital anomaly or birth defect, or any other event determined as SAE as per medical or scientific judgment.

  From Day 1 up to 24 weeks after Dose 3 (i.e., up to Day 351)

• Number of Participants With Medically Attended Adverse Events (MAAEs)

  MAAE was defined as an AE for which the participants received medical attention defined as hospitalization, or an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. Participants may have been counted more than once if they reported multiple episodes of the event for the different doses.

  Up to 28 days post any vaccination, and up to 28 days post each vaccination dose (i.e., post Dose 1 [at Day 29], Dose 2 [at Day 85], Dose 3 [at Day 211])

Study Arms (4)

Cohort 1: BNT165b1: 3 Micrograms (mcg)

EXPERIMENTAL

Participants received 3 intramuscular injections of 3 mcg of BNT165b1 vaccine, one each at Days 1, 57 and 183, respectively.

Biological: BNT165b1

Cohort 2: BNT165b1: 10 mcg

EXPERIMENTAL

Participants received 3 intramuscular injections of 10 mcg of BNT165b1 vaccine, one each at Days 1, 57 and 183, respectively.

Biological: BNT165b1

Cohort 3: BNT165b1: 30 mcg

EXPERIMENTAL

Participants received 3 intramuscular injections of 30 mcg of BNT165b1 vaccine, one each at Days 1, 57 and 183, respectively.

Biological: BNT165b1

Placebo

PLACEBO COMPARATOR

Participants received 3 intramuscular injections of matching placebo of BNT165b vaccine, one each at Days 1, 57 and 183, respectively.

Other: Placebo

Interventions

BNT165b1 BIOLOGICAL

RNA vaccine for active immunization against malaria administered as intramuscular injection.

Cohort 1: BNT165b1: 3 Micrograms (mcg); Cohort 2: BNT165b1: 10 mcg; Cohort 3: BNT165b1: 30 mcg

Placebo OTHER

Placebo matched to RNA vaccine administered as intramuscular injection.

Placebo

Eligibility Criteria

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

You may qualify if:

• Had given informed consent by signing and dating the informed consent form (ICF) before initiation of any trial-specific procedures
• Were willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions (e.g., to follow good practices to reduce their chances of being infected or spreading Coronavirus Disease 2019 \[COVID-19\]), and other requirements of the trial. This includes that they were able to understand and follow trial-related instructions
• Were aged 18 to 55 years, had a body mass index over 18.5 kg/m\^2 and under 35 kg/m\^2 and weighed at least 45 kg at Visit 0
• Were 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, were included
• Agreed not to enroll in another trial with an investigational medicinal product (IMP) starting from Visit 0 and until 12 weeks after receiving Dose 3
• Agreed not to travel to a malaria endemic region starting from Visit 0 and until 28 days after Dose 3, as defined per CDC (Centers for Disease Control and Prevention)
• Negative human immunodeficiency virus (HIV) -1 and -2 blood test result at Visit 0
• Negative severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) antigen test result at Visit 0
• Negative hepatitis B surface antigen (HBsAg) 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 was positive at Visit 0
• Volunteers of childbearing potential (VOCBP) who had a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test result at Visit 0 and negative urine pregnancy test results before each IMP administration. Volunteers born female who were postmenopausal or permanently sterilized were not considered VOBCP
• VOCBP who agreed to practice a highly effective form of contraception and required their male sexual partners to use condoms with a spermicidal agent, starting at Visit 0 and continuously until 90 days after receiving Dose 3
• VOCBP who agreed not to donate 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 were sexually active with partners of childbearing potential and who did not have a vasectomy that agreed to use condoms with a spermicidal agent and to practice a highly effective form of contraception with their sexual partners born female during the trial, starting at Visit 0 and continuously until 90 days after receiving Dose 3
• Men who were 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 malaria infection (any species) based on volunteer-reported medical history
• Travel to a malaria endemic region starting 6 months before Visit 0 and continuously until 28 days after receiving Dose 3, as defined per CDC
• Prior residence for greater than or equal to (\>=) 6 months in a malaria endemic region
• Were breastfeeding or had intended to become pregnant starting with Visit 0 and continuously until 90 days after receiving Dose 3 or fathered 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:
• Used a short-acting rescue inhaler (typically a beta 2 agonist) daily, or
• Used high dose inhaled corticosteroids (per American Academy of Allergy Asthma \& Immunology), or
• In the past year has had either of the following:
• Greater than one exacerbation of symptoms treated with oral/parenteral corticosteroids;
• Needed hospitalization, or intubation for asthma.
• Diabetes mellitus type 1 or type 2, including cases controlled with diet alone (Not excluded: history of isolated gestational diabetes).
• Hypertension:
• If a person had been found to have elevated blood pressure or hypertension during screening or previously, they were excluded for blood pressure that is not well controlled. Well controlled blood pressure was defined as consistently less than or equal to (\<=)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 enrollment.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (5)

Alliance for Multispecialty Research, LLC

Tempe, Arizona, 85281, United States

Location

University of Maryland, Center for Vaccine Development

Baltimore, Maryland, 21201, United States

Location

Alliance for Multispecialty Research, LLC

Las Vegas, Nevada, 89119, United States

Location

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37909, United States

Location

Clinical Trials of Texas, Inc.

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

Results Point of Contact

• Title: BioNTech clinical trials patient information
• Organization: BioNTech SE

patients@biontech.de

61319084

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 14, 2022
• Study Start: December 15, 2022
• Primary Completion: February 23, 2024
• Study Completion: September 6, 2024
• Last Updated: September 3, 2025
• Results First Posted: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)