Monkeypox
Conditions
Keywords
Prevention of mpox, Monkeypox virus, RNA vaccine, Vaccine, mpox, MPXV, Monkeypox
Brief summary
This was a dose-escalation, Phase I/II study evaluating the safety, tolerability, reactogenicity and immunogenicity of the investigational RNA-based multivalent vaccine candidate BNT166a for active immunization against monkeypox (mpox). This study was originally planned to include four substudies, i.e., substudy A (SSA), substudy B (SSB), substudy C (SSC), and substudy D (SSD). Sponsor decided not to conduct SSC, thus three substudies (SSA, SSB, and SSD) were conducted. In SSA and SSB, dosing started with an initial sentinel group, followed by the expansion cohort. In SSD, dosing was initiated after the interim analysis of SSA and SSB 1-month post-Dose 2 safety, reactogenicity, and immunogenicity data was received. This study was initially planned to investigate two vaccine candidates (the quadrivalent BNT166a and the trivalent BNT166c). The sponsor decided to not activate the groups with BNT166c.
Detailed description
Substudy A was an open-label, dose-escalation, Phase I substudy to assess the reactogenicity, safety, and immunogenicity of up to three dose levels of the multivalent vaccine candidate BNT166a in 48 healthy participants with no prior history of known or suspected smallpox vaccination (vaccinia-naïve participants). Substudy B was a one group, open-label, Phase I substudy to assess the reactogenicity, safety and immunogenicity of the multivalent vaccine candidate BNT166a in 16 healthy participants with prior history of smallpox vaccination (vaccinia-experienced). Substudy D was a one group, open-label, Phase IIa substudy to assess the reactogenicity, safety, and immunogenicity of one dose level of BNT166a in \ 32 healthy participants with no prior history of known or suspected smallpox vaccination (i.e., vaccinia-naïve participants). SSD was initiated after the interim analysis of SSA and SSB safety, reactogenicity, and immunogenicity data. The duration of study participation was \ 14 months per participant in all of the substudies.
Interventions
BIOLOGICALBNT166a
Multivalent ribonucleic acid (RNA)-based vaccine for active immunization against monkeypox administered as intramuscular injection.
Sponsors
BioNTech SE
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
(applicable to all substudies unless otherwise specified): * Had given informed consent by signing and dating the informed consent form (ICF) before initiation of any study-specific procedures. * Were willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study, including the prohibited concomitant medications. This included that they were able to understand and follow study-related instructions. * SSA and SSD only: Were 18 through 45 years of age (inclusive) at the time of informed consent. * SSB only: Were 50 through 65 years of age (inclusive) at the time of informed consent. * Had a body mass index over 18.5 kg/m\^2 and under 30 kg/m\^2 and weighed at least 50 kg at Visit 0. * Were healthy, in the clinical judgment of the investigator based on volunteer-reported medical history data, physical examination, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory test results. * SSA and SSD only: Had no prior history of known or suspected smallpox vaccination and no detectable smallpox vaccination characteristic scar (vaccinia-naïve participants). * SSB only: Had a history of prior smallpox vaccination (i.e., are vaccinia-experienced), determined based on medical records and/or presence of smallpox vaccination characteristic scar. The most recent smallpox vaccination was received before 1980. * Agreed not to enroll in another study with an investigational medicinal product starting from Visit 0 and until the end of this study. * Negative human immunodeficiency virus (HIV)-1 and HIV-2 antigen/antibody blood test result at Visit 0. * Negative Hepatitis B surface antigen and negative core antibodies test results and negative anti Hepatitis C virus antibodies (anti-HCV), or negative Hepatitis C virus (HCV) polymerase chain reaction test result if the anti-HCV was positive at Visit 0. * Volunteers of childbearing potential (VOCBP) must not have been pregnant. VOCBP and men who were sexually active with partners of childbearing potential and their sexual partners born female should have used a highly effective form of contraception from at least 28 days prior to Dose 1 up to at least 90 days after receiving the last dose of study treatment, and should have agreed not to donate eggs (ova, oocytes) or sperm.
Exclusion criteria
(applicable to all substudies unless otherwise specified): * History of mpox, smallpox or vaccinia infection based on volunteer-reported medical history. * Pregnant, breastfeeding, were planning pregnancy or were planning to father children starting from Visit 0 and continuously until 90 days after receiving Dose 2. * History of known or suspected severe adverse reaction including allergic reaction (e.g., anaphylaxis) to vaccines or to vaccine components such as lipids. * Current or history of the following medical conditions at Visit 0 or Visit 1: * Uncontrolled, moderate or severe asthma; asthma severity as defined in the US National Asthma Education and Prevention Program Expert Panel report * Chronic obstructive pulmonary disease. * 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 hypertension, excluded for blood pressure that was not well controlled. Well controlled blood pressure was 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 have been \<150 mm Hg systolic and \<100 mm Hg. * Systolic blood pressure \>=150 mm Hg or diastolic blood pressure \>=100 mm Hg. * Malignancy, excluding localized basal or squamous cell cancer. * Cardiovascular diseases, (e.g., myocarditis, pericarditis, coronary heart disease, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, stroke or transient ischemic attack). * Bleeding disorders (e.g., factor deficiency, coagulopathy, or platelet disorder). * Seizure disorder: History of seizure(s) within past 3 years; used medications in order to prevent or treat seizure(s) at any time within the past 3 years. * Estimated glomerular filtration rate \<60 mL/min/1.73 m\^2. * Chronic liver disease. * Schizophrenia, major depressive disorder, suicidal ideation. Such psychiatric illnesses, as bipolar disorder, autism and attention deficit-hyperactivity disorder that at the discretion of the investigator could interfere with participation and follow-up as outlined by the study. * Current or history of the following diseases associated with immune dysregulation: * Known or suspected immunodeficiency. * History of solid organ or bone marrow transplantation. * Asplenia: any condition resulting in the absence of a functional spleen. * Currently existing or history of any autoimmune disease. * SSA and SSB: At Visit 0, any screening hematology and/or blood chemistry laboratory value that met the definition of a Grade \>=1 abnormality (according to the FDA toxicity grading scale; see separate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Solicited Local Reactions At the Injection Site | Up to 7 days post any vaccination, and up to 7 days post each vaccination dose (that is, post-dose 1 [up to Day 8]) and post-dose 2 [up to Day 38]) | All reactogenicity events information recorded via the participant e-diaries or solicited by the investigator were considered as solicited events. Solicited local reactions were: pain at the injection site, erythema/redness, and induration/swelling. Any local reaction indicates participants with any reactions, including reactions that do not qualify for Grade 1 (\<2.5 cm for erythema/redness or induration/swelling). The intensity of local reaction was assessed by the participant and may be confirmed or corrected by the investigator; grades were defined as Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially life-threatening. |
| Number of Participants Reporting Solicited Systemic Events | Up to 7 days post any vaccination, and up to 7 days post each vaccination dose (that is, post Dose 1 [up to Day 8] and post Dose 2 [up to Day 38]) | All reactogenicity events information recorded via the participant e-diaries or solicited by the investigator were considered as solicited events. Solicited systemic reactions were: fever, chills, fatigue/tiredness, headache, muscle pain/myalgia, joint pain/arthralgia, vomiting, and diarrhea. Any systemic reaction indicated participants with any Grade \>=1 reactions. The intensity of systemic events was assessed by the participants and may be confirmed or corrected by the investigator; grades were defined as Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially life-threatening. |
| Number of Participants With At Least One Unsolicited Adverse Event (AE) | Up to 28 days post any vaccination, and up to 28 days post each vaccination dose (that is, post-dose 1 [up to Day 29] and post-Dose 2 [up to Day 59]) | 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. All AE information or safety data including solicited events persisting beyond 7 days that were voluntarily communicated by the participant or collected by the investigator (that is, ECG or laboratory results etc.) were considered unsolicited events. 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. |
| Number of Participants With At Least One Serious Adverse Event (SAE) | From Dose 1 up to Day 201 | 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 At Least One Adverse Event of Special Interest (AESI) | From Dose 1 up to Day 201 | An AESI, serious or non-serious, was one of scientific and medical concern specific to the sponsor's product or program, for which monitoring and rapid communication by the investigator to the sponsor was appropriate. |
Countries
United Kingdom, United States
Contacts
STUDY_DIRECTORBioNTech Responsible Person
BioNTech SE
Participant flow
Pre-assignment details
This study consisted of 3 sub-studies Substudy A (SSA), Substudy B (SSB) and Substudy D (SSD). In total, 96 participants were assigned to treatment groups as specified in data table below. Substudy C (SSC) was planned; however, it was not initiated, as the sponsor decided not to conduct it. Results are based on primary completion date of 25 August 2025.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 36.9 years STANDARD_DEVIATION 11.72 |
| Body Mass Index (BMI) | 24.327 kilogram per meter square (kg/m^2) STANDARD_DEVIATION 2.9371 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 74 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 32 |
| other Total, other adverse events | 10 / 16 | 11 / 16 | 8 / 16 | 11 / 16 | 15 / 32 |
| serious Total, serious adverse events | 2 / 16 | 0 / 16 | 0 / 16 | 1 / 16 | 0 / 32 |
Outcome results
None listed