| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Protection against COVID-19 | |
| E.1.1.1 | Medical condition in easily understood language | prevention of infection with the Corona virus
| |
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10051905 | | E.1.2 | Term | Coronavirus infection | | E.1.2 | System Organ Class | 10021881 - Infections and infestations | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | Phase 1:
-To describe the safety and tolerability profiles of prophylactic BNT162b2 at each dose level in each age group.
Phase 2/3: Primary Safety:
- To define the safety profile of prophylactic BNT162b2 in all participants (selected-dose and obtaining-serum-samples-for-potential-troponin I testing portions of the study) in Phase 2/3 in each age group
Primary Immunogenicity (Selected dose 2-Dose series):
- To immunobridge the immune response elicited by prophylactic BNT162b2 between Ph 2/3 participants at the dose selected in each age group and participants 16 to 25 years of age from the C4591001 study without serological or virological evidence (up to 1 month after receipt of Dose 2) of past SARS-CoV-2 infection
(For age groups, please refer to the protocol.)
Primary Immunogenicity (Selected-Dose 3-Dose Series)
(For further objectives, please refer to the Protocol.) | |
| E.2.2 | Secondary objectives of the trial | Phase 1:
- To describe the immune responses elicited by prophylactic BNT162b2 at each dose level in each age group
Phase 2/3:
Secondary Immunogenicity/Efficacy:
- To describe the immune responses elicited by prophylactic BNT162b2 at the dose level selected in each age group in Phase 2/3 participants without serological or virological evidence of past SARS-CoV-2 infection
- For further secondary endpoints, please refer to the protocol. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Age and Sex:
1. Male or female participants between =6 months and <12 years of age, at the time of randomization, at Visit 1 for the dose-finding/selected-dose evaluation
For the obtaining-serum samples-for-potential-troponin I testing portion of the study:
• Male or female participants between ≥5 and <16 years of age.
• Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1)
and female (Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Participants' parent(s)/legal guardian(s) and participants, as age
appropriate, who are willing and able to comply with all scheduled visits,
treatment plan, laboratory tests, lifestyle considerations, and other
study procedures.
3. Healthy participants who are determined by medical history, physical
examination, and clinical judgment of the investigator to be eligible for
inclusion in the study.
Note: Healthy participants with preexisting stable disease, defined as
disease not requiring significant change in the therapy or hospitalization
for worsening disease during the 6 weeks before enrollment, can be
included.
Phase 2/3: Specific criteria for such participants with known stable
infection with HIV, HCV, or HBV can be found in Section 10.7.
4. Participants are expected to be available for the duration of the study
and whose parent(s)/legal guardian can be contacted by telephone
during study participation.
5. Negative urine pregnancy test for female participants who are
biologically capable of having children.
6. Female participant of childbearing potential or male participant able to
father children who is willing to use a highly effective method of
contraception as outlined in this protocol for at least 28 days after the
last dose of study intervention if at risk of pregnancy with her/his
partner; or female participant not of childbearing potential or male
participant not able to father children.
Informed Consent:
7. The participant or participant's parent(s)/legal guardian is capable of
giving signed informed consent as described in Appendix 1, which
includes compliance with the requirements and restrictions listed in the
ICD and in this protocol. Depending on the age of the participant and
according to local requirements, participants will also be asked to
provide assent as appropriate (verbal or written).
The investigator, or a person designated by the investigator, will obtain
written or electronically signed informed consent (and assent) from each
study participant or participant's legal guardian (as defined in Appendix
1) and the participant's assent, when applicable, before any studyspecific
activity is performed. All legal guardians should be fully
informed, and participants should be informed to the fullest extent
possible, about the study in language and terms they are able to
understand. The investigator will retain the original copy of each
participant's signed consent/assent document. | |
| E.4 | Principal exclusion criteria | Medical Conditions:
1. Phase 1 only: Past clinical (based on COVID-19 symptoms/signs
alone, if a SARS CoV 2 NAAT result was not available) or microbiological
(based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT
result) diagnosis of COVID 19.
2. Phase 1 only: Known infection with HIV, HCV, or HBV.
3. Receipt of medications intended to prevent COVID-19.
4. Previous or current diagnosis of MIS-C.
5. Other medical or psychiatric condition including recent (within the
past year) or active suicidal ideation/behavior or laboratory abnormality
that may increase the risk of study participation or, in the investigator's
judgment, make the participant inappropriate for the study. Note: This
includes both conditions that may increase the risk associated with
study intervention administration or a condition that may interfere with
the interpretation of study results
6. History of severe adverse reaction associated with a vaccine and/or
severe allergic reaction (eg, anaphylaxis) to any component of the study
intervention(s).
7. Immunocompromised individuals with known or suspected
immunodeficiency, as determined by history and/or laboratory/physical
examination.
8. Individuals with a history of autoimmune disease or an active
autoimmune disease requiring therapeutic intervention, including but
not limited to systemic lupus erythematosus. Note: Stable type 1
diabetes and hypothyroidism are permitted.
9. Bleeding diathesis or condition associated with prolonged bleeding
that would, in the opinion of the investigator, contraindicate
intramuscular injection.
10. Female who is pregnant or breastfeeding.
Prior/Concomitant Therapy:
11. Previous vaccination with any coronavirus vaccine.
12. Individuals who receive treatment with immunosuppressive therapy,
including cytotoxic agents or systemic corticosteroids, eg, for cancer or
an autoimmune disease, or planned receipt throughout the study. If
systemic corticosteroids have been administered short term (<14 days)
for treatment of an acute illness, participants should not be enrolled into
the study until corticosteroid therapy has been discontinued for at least
28 days before study intervention administration. Inhaled/nebulized,
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are
permitted.
13. Receipt of blood/plasma products, immunoglobulin, or monoclonal
antibodies, from 60 days before study intervention administration, or
receipt of any passive antibody therapy specific to COVID-19 from 90
days before study intervention administration, or planned receipt
throughout the study.
Prior/Concurrent Clinical Study Experience:
14. Participation in other studies involving study intervention within 28
days prior to study entry and/or during study participation.
15. Previous participation in other studies involving study intervention
containing LNPs.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
16. Participants who are direct descendants (child or grandchild) of
investigational site staff members or Pfizer/BioNTech employees directly
involved in the conduct of the study, site staff otherwise supervised by
the investigator, and their respective family members. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | Phase 1:
Participants =5 to <12 and =2 to <5 years of age:
• Local reactions (pain at the injection site, redness, and swelling)
• Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea,
new or worsened muscle pain, and new or worsened joint pain)
• AEs
• SAEs
Participants ≥6 months to <2 years of age:
• Local reactions (tenderness at the injection site, redness, and
swelling)
• Systemic events (fever, decreased appetite, drowsiness, and
irritability)
• AEs
• SAEs
Phase 2/3
Primary Safety:
Participants =12 to <16, =5 to <12 and =2 to <5 years of age:
• Local reactions (pain at the injection site, redness, and swelling)
• Systemic events (fever, fatigue, headache, chills, vomiting, diarrhea,
new or worsened muscle pain, and new or worsened joint pain)
• AEs
• SAEs
Participants ≥6 months to <2 years of age:
• Local reactions (tenderness at the injection site, redness, and
swelling)
• Systemic events (fever, decreased appetite, drowsiness, and
irritability)
• AEs
• SAEs
Primary Immunogenicity (Selected dose 2-Dose Series):
•SARS-CoV-2 neutralizing titers
Primary Immunogenicity (Selected-Dose 3-Dose Series):
•SARS-CoV-2 neutralizing titers | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | Please see the clinical study protocol Section 3 | |
| E.5.2 | Secondary end point(s) | Phase 1:
• SARS CoV 2 neutralizing titers
Phase 2/3:
Secondary Immunogenicity/Efficacy:
- SARS-CoV-2 neutralizing titers
Secondary Efficacy (Selected-Dose 2-Dose Series):
- Confirmed COVID-19 incidence from 7 days after Dose 2 to prior to
Dose 3 per 1000 person-years of blinded follow-up
Secondary Efficacy (Selected-Dose 3-Dose Series):
•Confirmed COVID-19 incidence from 7 days after Dose 3 per 1000
person-years of blinded follow-up | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | | Please see the clinical study protocol Section 3 | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description | | A Phase 1/2/3 Study to Evaluate the Safety, Tolerability, and Immunogenicity | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description | |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Argentina | | Brazil | | Finland | | Mexico | | Poland | | Spain | | United States | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | A participant is considered to have completed the study if he/she has completed all phases of the study, including the last visit.
The end of the study is defined as the date of the last visit of the last participant in the study.
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 29 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 6 |
