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A Clinical Study Investigating the Safety and Immune Responses After Immunization With Investigational Monkeypox Vaccines

Primary Purpose

Monkeypox

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BNT166a
BNT166c
Sponsored by
BioNTech SE
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Monkeypox focused on measuring Prevention of monkeypox, Monkeypox virus, RNA vaccine, Vaccine, mpox

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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, and other requirements of the trial, including the prohibited concomitant medications. This includes that they are able to understand and follow trial-related instructions. SSA only: Are 18 through 45 years of age (inclusive) at the time of informed consent. SSB only: Are 50 through 65 years of age (inclusive) at the time of informed consent. Have a body mass index over 18.5 kg/m^2 and under 30 kg/m^2 and weigh at least 50 kg at Visit 0. Are 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 only: Have no prior history of known or suspected smallpox vaccination and no detectable smallpox vaccination characteristic scar (vaccinia-naïve subjects). SSB only: Have 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 should have been received before 1980. Agree not to enroll in another trial with an IMP starting from Visit 0 and until the end of this trial (Visit 12). Negative human immunodeficiency virus (HIV)-1 and HIV-2 antigen/antibody blood test result at Visit 0. Negative Hepatitis B surface antigen test result and negative anti Hepatitis C virus antibodies (anti-HCV), or negative Hepatitis C virus (HCV) polymerase chain reaction (PCR) test result if the anti-HCV is positive at Visit 0. Volunteers of childbearing potential (VOCBP) must not be pregnant. VOCBP and men who are sexually active with partners of childbearing potential and their sexual partners born female should use 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 trial treatment, and should agree not to donate eggs (ova, oocytes) or sperm. Exclusion Criteria: History of mpox, smallpox or vaccinia infection based on volunteer-reported medical history. Pregnant, breastfeeding, planning pregnancy or 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 has hypertension, 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. 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; use of 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 trial. 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. At Visit 0, any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade ≥1 abnormality (according to the toxicity grading scale; see separate criteria for indirect bilirubin and troponin I). Individuals with any stable Grade 1 abnormalities may be considered eligible at the discretion of the investigator. A stable Grade 1 laboratory abnormality is defined as the value which is ≤ Grade 1 upon repeated testing on a second sample from this individual during the screening period (prior to Visit 1). Individuals with abnormal but not clinically significant parameters not included in the toxicity guidance may be considered eligible at discretion of investigator. Abnormal total bilirubin at Visit 0. Note: inclusion of volunteers with bilirubin ≤1.25 upper limit of normal (ULN) if due to Gilbert's syndrome is allowed. Any abnormal troponin I value at Visit 0. A 12-lead ECG at Visit 0 which is consistent with probable or possible myocarditis/pericarditis or which demonstrates clinically relevant abnormalities that may affect subject safety or are otherwise clinically significant findings (e.g., complete left bundle branch block, AV block, average corrected QT interval by Fridericia (QTcF interval) >450 msec, signs of myocardial infarction, ST elevation consistent with myocardial ischemia, or serious brady- or tachyarrhythmias). Febrile illness (body temperature ≥38.0°C) or other acute illness within 48 hours prior to Dose 1 and/or current (if presented at Visit 1, temporary deferral is allowed). Participation or planned participation in strenuous or endurance exercise within 7 days before or after each IMP administration. SSA only: Vaccination with any Orthopoxvirus-based vaccine including vaccines for prevention of smallpox, disease caused by vaccinia virus or mpox, or vector Orthopoxvirus-based vaccines. SSB only: Vaccination for prevention of mpox or disease caused by vaccinia virus, or with vector Orthopoxvirus-based vaccine. Vaccination for prevention of smallpox done in or after 1980. Any vaccination within 28 days before Dose 1. Seasonal inactivated influenza vaccine is allowed, however, it should be administered at least 14 days before IMP administration. Any non-trial IMP within 28 days or five half-lives (whichever is longer) before Dose 1. Blood/plasma products and/or immunoglobulins within 120 days before Dose 1. Allergy treatment with antigen injections within 14 days before Dose 1. Immunosuppressive therapy, including corticosteroids, or radiotherapy within 6 months or five half-lives (whichever is longer) before Dose 1. If systemic corticosteroids have been administered short term (≤14 days, at a dose of ≤20 mg/day of prednisone or equivalent) for treatment of an acute illness, individuals should be enrolled in the trial only after corticosteroid therapy has been discontinued for at least 28 days before Dose 1. Intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. Have a history of alcohol abuse within 1 year before Visit 0 or have a history of substance abuse within the past 5 years before Visit 0. Are vulnerable individuals as per ICH E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.

Sites / Locations

  • California Research FoundationRecruiting
  • University Hospital SouthamptonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

SSA - BNT166a

SSA - BNT166c

SSB - BNT166a

SSB - BNT166c

Arm Description

Escalating dose levels

One dose level

One dose level

One dose level

Outcomes

Primary Outcome Measures

SSA and SSB - Proportion (%) of subjects reporting solicited local reactions at the injection site up to 7 days after each investigational medicinal product (IMP) dose for each group
For each group
SSA and SSB - Proportion (%) of subjects reporting solicited systemic events up to 7 days after each IMP dose for each group
For each group
SSA and SSB - Proportion (%) of subjects with at least one unsolicited adverse event (AE) occurring from Dose 1 to 28 days after the dose
For each group
SSA and SSB - Proportion (%) of subjects with at least one unsolicited AE occurring from Dose 2 to 28 days after the dose
For each group
SSA and SSB - Proportion (%) of subjects with at least one serious adverse event (SAE) occurring from Dose 1 to 24 weeks after Dose 2
For each group
SSA and SSB - Proportion (%) of subjects with worsening grading shifts in hematology and chemistry laboratory values between baseline and 1 week after Dose 1, before Dose 2, 1 week and 1 month after Dose 2
For each group

Secondary Outcome Measures

Full Information

First Posted
August 4, 2023
Last Updated
October 24, 2023
Sponsor
BioNTech SE
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1. Study Identification

Unique Protocol Identification Number
NCT05988203
Brief Title
A Clinical Study Investigating the Safety and Immune Responses After Immunization With Investigational Monkeypox Vaccines
Official Title
A Randomized, Partially Observer-blind, Dose-escalation, Phase I/II Trial Evaluating the Safety and Immunogenicity of Investigational RNA-based Mpox Vaccine Candidates
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 21, 2023 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioNTech SE

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a randomized, partially observer-blind, dose-escalation, Phase I/II trial evaluating the safety, tolerability, reactogenicity and immunogenicity of investigational RNA-based multivalent vaccine candidates (BNT166a and BNT166c) for active immunization against monkeypox (mpox). This trial will start with the two substudies, i.e., substudy A (SSA) and substudy B (SSB). This trial will be initiated with the dose-escalation SSA. In each substudy, dosing will start with an initial sentinel group, followed by the expansion cohort.
Detailed Description
Substudy A is an open-label, dose-escalation, Phase I substudy to assess the reactogenicity, safety and immunogenicity of up to three dose levels of two multivalent vaccine candidates (BNT166a and BNT166c) in ~64 healthy participants with no prior history of known or suspected smallpox vaccination (vaccinia-naïve participants). Two doses will be given ~31 days apart. The sponsor may decide to not activate the group with BNT166c, in this case there will be no randomization. Substudy B is a randomized, observer-blinded and sponsor-unblinded Phase I substudy to assess the reactogenicity, safety and immunogenicity of two multivalent vaccine candidates (BNT166a and BNT166c) in ~32 healthy participants with prior history of smallpox vaccination (vaccinia-experienced).Two doses will be given ~31 days apart. Participants will be randomized 1:1. Sponsor may decide to not activate one of the groups, in that case this substudy will be a one group open-label substudy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Monkeypox
Keywords
Prevention of monkeypox, Monkeypox virus, RNA vaccine, Vaccine, mpox

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
SSA: open-label; SSB: observer-blinded and sponsor-unblinded
Allocation
Randomized
Enrollment
96 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SSA - BNT166a
Arm Type
Experimental
Arm Description
Escalating dose levels
Arm Title
SSA - BNT166c
Arm Type
Experimental
Arm Description
One dose level
Arm Title
SSB - BNT166a
Arm Type
Experimental
Arm Description
One dose level
Arm Title
SSB - BNT166c
Arm Type
Experimental
Arm Description
One dose level
Intervention Type
Biological
Intervention Name(s)
BNT166a
Intervention Description
Multivalent ribonucleic acid (RNA)-based vaccine for active immunization against monkeypox administered as intramuscular injection
Intervention Type
Biological
Intervention Name(s)
BNT166c
Intervention Description
Multivalent RNA-based vaccine for active immunization against monkeypox administered as intramuscular injection
Primary Outcome Measure Information:
Title
SSA and SSB - Proportion (%) of subjects reporting solicited local reactions at the injection site up to 7 days after each investigational medicinal product (IMP) dose for each group
Description
For each group
Time Frame
Up to 7 day after each IMP dose
Title
SSA and SSB - Proportion (%) of subjects reporting solicited systemic events up to 7 days after each IMP dose for each group
Description
For each group
Time Frame
Up to 7 day after each IMP dose
Title
SSA and SSB - Proportion (%) of subjects with at least one unsolicited adverse event (AE) occurring from Dose 1 to 28 days after the dose
Description
For each group
Time Frame
From Dose 1 to 28 days after Dose 1
Title
SSA and SSB - Proportion (%) of subjects with at least one unsolicited AE occurring from Dose 2 to 28 days after the dose
Description
For each group
Time Frame
From Dose 2 to 28 days after Dose 2
Title
SSA and SSB - Proportion (%) of subjects with at least one serious adverse event (SAE) occurring from Dose 1 to 24 weeks after Dose 2
Description
For each group
Time Frame
From Dose 1 to 24 weeks after Dose 2
Title
SSA and SSB - Proportion (%) of subjects with worsening grading shifts in hematology and chemistry laboratory values between baseline and 1 week after Dose 1, before Dose 2, 1 week and 1 month after Dose 2
Description
For each group
Time Frame
From baseline to 1 month after Dose 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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, and other requirements of the trial, including the prohibited concomitant medications. This includes that they are able to understand and follow trial-related instructions. SSA only: Are 18 through 45 years of age (inclusive) at the time of informed consent. SSB only: Are 50 through 65 years of age (inclusive) at the time of informed consent. Have a body mass index over 18.5 kg/m^2 and under 30 kg/m^2 and weigh at least 50 kg at Visit 0. Are 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 only: Have no prior history of known or suspected smallpox vaccination and no detectable smallpox vaccination characteristic scar (vaccinia-naïve subjects). SSB only: Have 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 should have been received before 1980. Agree not to enroll in another trial with an IMP starting from Visit 0 and until the end of this trial (Visit 12). Negative human immunodeficiency virus (HIV)-1 and HIV-2 antigen/antibody blood test result at Visit 0. Negative Hepatitis B surface antigen test result and negative anti Hepatitis C virus antibodies (anti-HCV), or negative Hepatitis C virus (HCV) polymerase chain reaction (PCR) test result if the anti-HCV is positive at Visit 0. Volunteers of childbearing potential (VOCBP) must not be pregnant. VOCBP and men who are sexually active with partners of childbearing potential and their sexual partners born female should use 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 trial treatment, and should agree not to donate eggs (ova, oocytes) or sperm. Exclusion Criteria: History of mpox, smallpox or vaccinia infection based on volunteer-reported medical history. Pregnant, breastfeeding, planning pregnancy or 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 has hypertension, 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. 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; use of 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 trial. 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. At Visit 0, any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade ≥1 abnormality (according to the toxicity grading scale; see separate criteria for indirect bilirubin and troponin I). Individuals with any stable Grade 1 abnormalities may be considered eligible at the discretion of the investigator. A stable Grade 1 laboratory abnormality is defined as the value which is ≤ Grade 1 upon repeated testing on a second sample from this individual during the screening period (prior to Visit 1). Individuals with abnormal but not clinically significant parameters not included in the toxicity guidance may be considered eligible at discretion of investigator. Abnormal total bilirubin at Visit 0. Note: inclusion of volunteers with bilirubin ≤1.25 upper limit of normal (ULN) if due to Gilbert's syndrome is allowed. Any abnormal troponin I value at Visit 0. A 12-lead ECG at Visit 0 which is consistent with probable or possible myocarditis/pericarditis or which demonstrates clinically relevant abnormalities that may affect subject safety or are otherwise clinically significant findings (e.g., complete left bundle branch block, AV block, average corrected QT interval by Fridericia (QTcF interval) >450 msec, signs of myocardial infarction, ST elevation consistent with myocardial ischemia, or serious brady- or tachyarrhythmias). Febrile illness (body temperature ≥38.0°C) or other acute illness within 48 hours prior to Dose 1 and/or current (if presented at Visit 1, temporary deferral is allowed). Participation or planned participation in strenuous or endurance exercise within 7 days before or after each IMP administration. SSA only: Vaccination with any Orthopoxvirus-based vaccine including vaccines for prevention of smallpox, disease caused by vaccinia virus or mpox, or vector Orthopoxvirus-based vaccines. SSB only: Vaccination for prevention of mpox or disease caused by vaccinia virus, or with vector Orthopoxvirus-based vaccine. Vaccination for prevention of smallpox done in or after 1980. Any vaccination within 28 days before Dose 1. Seasonal inactivated influenza vaccine is allowed, however, it should be administered at least 14 days before IMP administration. Any non-trial IMP within 28 days or five half-lives (whichever is longer) before Dose 1. Blood/plasma products and/or immunoglobulins within 120 days before Dose 1. Allergy treatment with antigen injections within 14 days before Dose 1. Immunosuppressive therapy, including corticosteroids, or radiotherapy within 6 months or five half-lives (whichever is longer) before Dose 1. If systemic corticosteroids have been administered short term (≤14 days, at a dose of ≤20 mg/day of prednisone or equivalent) for treatment of an acute illness, individuals should be enrolled in the trial only after corticosteroid therapy has been discontinued for at least 28 days before Dose 1. Intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. Have a history of alcohol abuse within 1 year before Visit 0 or have a history of substance abuse within the past 5 years before Visit 0. Are vulnerable individuals as per ICH E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
BioNTech clinical trials patient information
Phone
+49 6131 9084
Ext
0
Email
patients@biontech.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
BioNTech Responsible Person
Organizational Affiliation
BioNTech SE
Official's Role
Study Director
Facility Information:
Facility Name
California Research Foundation
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Recruiting
Facility Name
University Hospital Southampton
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Clinical Study Investigating the Safety and Immune Responses After Immunization With Investigational Monkeypox Vaccines

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