An Exploratory Phase I, Randomized, Observer-blind, Placebo-controlled Dose Escalation Trial Evaluating the Safety, Tolerability and Immunogenicity of an Investigational RNA-based Vaccine for Active Immunization Against Malaria
Overview
- Phase
- Phase 1
- Intervention
- BNT165b1
- Conditions
- Malaria
- Sponsor
- BioNTech SE
- Enrollment
- 60
- Locations
- 3
- Primary Endpoint
- Number of Participants With Solicited Local Reactions
- Status
- Completed
- Last Updated
- 8 months ago
Overview
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.
Detailed Description
The trial had enrolled participants into three cohorts by dose level who were randomized 4:1 to BNT165b1: placebo. The trial used a staggered dose escalation schema with sentinel participants for Dose 1 in all cohorts.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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:
Arms & Interventions
Cohort 3: BNT165b1: 30 mcg
Participants received 3 intramuscular injections of 30 mcg of BNT165b1 vaccine, one each at Days 1, 57 and 183, respectively.
Intervention: BNT165b1
Placebo
Participants received 3 intramuscular injections of matching placebo of BNT165b vaccine, one each at Days 1, 57 and 183, respectively.
Intervention: Placebo
Cohort 1: BNT165b1: 3 Micrograms (mcg)
Participants received 3 intramuscular injections of 3 mcg of BNT165b1 vaccine, one each at Days 1, 57 and 183, respectively.
Intervention: BNT165b1
Cohort 2: BNT165b1: 10 mcg
Participants received 3 intramuscular injections of 10 mcg of BNT165b1 vaccine, one each at Days 1, 57 and 183, respectively.
Intervention: BNT165b1
Outcomes
Primary Outcomes
Number of Participants With Solicited Local Reactions
Time Frame: 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])
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.
Number of Participants With Solicited Systemic Reactions
Time Frame: 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])
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.
Number of Participants With Adverse Events (AEs)
Time Frame: 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])
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.
Number of Participants With Serious Adverse Events (SAEs)
Time Frame: From Day 1 up to 24 weeks after Dose 3 (i.e., up to Day 351)
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.
Number of Participants With Medically Attended Adverse Events (MAAEs)
Time Frame: 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])
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.