Primary Safety Objective: To describe the safety profile of 20vPnC
ID
Source
Brief title
Condition
- Therapeutic procedures and supportive care NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Safety Objective:
- To describe the safety profile of 20vPnC
Primary Concomitant Immunogenicity Objective
- To demonstrate that the immune responses induced by concomitant vaccine
antigens given with 20vPnC are noninferior to immune responses induced by
concomitant vaccine antigens given with 13vPnC at 1 month after Dose 3
Primary Pneumococcal Immunogenicity Objectives:
- To demonstrate that the percentages of participants with predefined
serotype-specific IgG concentrations for the 13 serotypes in the 20vPnC group
are noninferior to the percentages of the corresponding serotypes in the 13vPnC
group at 1 month after Dose 3
- To demonstrate that the percentages of participants with predefined
serotype-specific IgG concentrations for the 7 additional serotypes in the
20vPnC group are noninferior to the lowest percentage among the 13 serotypes in
the 13vPnC group at 1 month after Dose 3
- To demonstrate that the serotype- specific IgG GMCs for the 13 serotypes in
the 20vPnC group are noninferior to the GMCs for
the corresponding serotypes in the 13vPnC group at 1 month after Dose 3
-To demonstrate that the serotype- specific IgG GMCs for the 7 additional
serotypes in the 20vPnC group are noninferior to the lowest IgG GMCs among the
13 serotypes in the 13vPnC group at 1 month after Dose 3
Secondary outcome
Secondary Pneumococcal Immunogenicity Objective:
- To further describe the immune responses induced by 20vPnC
Secondary Concomitant Immunogenicity Objective
- To further describe the immune responses induced by specific concomitant
vaccine antigens given with 20vPnC or 13vPnC
-
Background summary
2.1 Study Rationale
This study is part of the Phase 3 clinical development program to support the
use of 20vPnC in the pediatric population. The purpose of the study is to
generate key safety and immunogenicity data to support licensure in this
population. The targeted age of the population for this study, infants born at
>36 weeks of gestation and *42 to *112 days of age, has been selected as the
routinely recommended vaccination schedule for pneumococcal conjugate vaccines
and other vaccines in infants, starting at approximately 2 months of age.
The participants will be administered either 20vPnC or 13vPnC in a series of 2
infant doses and 1 toddler dose (at 2, 4, and 11-12 months of age). Data will
also be generated on key routine pediatric vaccines given concomitantly with
20vPnC or 13vPnC.
Study objective
Primary Safety Objective: To describe the safety profile of 20vPnC
Study design
4.1 Overall Design
This Phase 3, multicenter, randomized, double-blind study will be conducted at
investigator sites in Europe, and possibly other countries. This study is part
of the Phase 3 pediatric clinical development program to support the use of
20vPnC in the pediatric population. The purpose of the study is to generate
data on the safety and immunogenicity of 20vPnC in infants when administered in
a series of 2 infant doses and 1 toddler dose (at 2, 4, and
11-12 months of age). Data will also be generated on key routine pediatric
vaccines given concomitantly with 20vPnC or 13vPnC. 13vPnC will serve as an
active comparator.
Approximately 1200 infants >36 weeks of gestation and *42 to *112 days of age
at the time of consent by a parent(s)/legal guardian(s) will be enrolled into
this study. Participants will be randomized in a 1:1 ratio to receive either
20vPnC or 13vPnC (control vaccine) by site- based randomization. At 2, 4, and
11 to 12 months of age (Doses 1 [Visit 1], 2 [Visit 2], and 3 [Visit 4],
respectively), participants will receive the same vaccine (either 20vPnC or
13vPnC) for all 3 doses. Blood will be drawn from all participants for
immunogenicity assessments 1 month after Dose 2 (5 months of age), prior to
receipt of Dose 3 (11-12 months of age), and 1 month after Dose 3 (13 months of
age). A subset of participants (participants at certain investigator sites)
will also have blood drawn for immunogenicity assessments prior to Dose 1 and
prior to Dose 2.
On Day 1 (Visit 1, Dose 1 vaccination) of the study, participants will be
assessed for eligibility and information will be collected, including medical
history and vaccine history. Vaccines administered during pregnancy and
intrapartum antibiotic use (yes/no) will also be collected (if available). In a
subset of participants (participants at selected investigator sites), blood
will be drawn prior to Dose 1. All participants will receive Dose 1 of 20vPnC
or 13vPnC. The 13vPnC and 20vPnC will be matched in appearance and will be
prepared and administered by a site staff member or designee. Specific
concomitant vaccination containing DTaP, HBV, IPV, and Hib antigens will also
be administered at this visit.
Participants will be observed for 30 minutes after vaccination, and any
reactions occurring during that time will be recorded as AEs.
The participant*s parent(s)/legal guardian(s) will be provided with an e-diary
(or e-diary application), digital thermometer, and measuring device and
instructed to collect prompted local reactions (redness, swelling, and pain at
the injection site) and systemic events (fever, decreased appetite,
drowsiness/increased sleep, and irritability) occurring 7 days after each
vaccination. Use of antipyretic/pain medications will also be prompted for and
collected daily in the e-diary for 7 days after vaccination. The participant*s
parent(s)/legal guardian(s) will be instructed to contact the study staff if
the participant experiences redness or swelling
>14 caliper units, severe pain at the 20vPnC or 13vPnC injection site, or fever
>40.0°C (>104.0°F) in the 7 days after vaccination, or has an emergency room
visit or hospitalization.
Participants will return for Visit 2 (42 to 63 days after Visit 1).
Participants will be assessed for continued eligibility and information will be
collected from the participant*s parent(s)/legal guardian(s) on AEs, including
nonserious AEs, SAEs, NDCMCs, and e-diary follow-up (as needed). Concomitant
medications used to treat SAEs and NDCMCs will be recorded, as will information
on nonstudy vaccinations given since the last visit. An NDCMC is defined as a
significant disease or medical condition, not previously identified, that is
expected to be persistent or is otherwise long-lasting in its effects. A subset
of participants will have blood drawn for immunogenicity assessment at this
visit prior to
Dose 2. Dose 2 of 20vPnC or 13vPnC will be administered. Specific concomitant
vaccination containing DTaP, HBV, IPV, and Hib antigens will also be
administered at this visit. Participants will be observed for 30 minutes after
vaccination and any reactions occurring during that time will be recorded as
AEs. The participant*s parent(s)/legal guardian(s) will be instructed to
collect prompted local reactions and systemic events occurring 7 days after
vaccination. Use of antipyretic/pain medications will also be
prompted for and collected daily in the e-diary for 7 days after vaccination.
The participant*s parent(s)/legal guardian(s) will be instructed to contact the
study staff if the participant experiences redness or swelling >14 caliper
units, severe pain at the 20vPnC or 13vPnC injection site, or fever >40.0°C
(>104.0°F) in the 7 days after vaccination or has an emergency room visit or
hospitalization.
Participants will return for Visit 3 (28 to 42 days after Visit 2).
Participants will be assessed for continued eligibility and information will be
collected from the participant*s parent(s)/legal guardian(s) on AEs, SAEs,
NDCMCs, and e-diary follow-up (as needed). The e-diary will be collected (if
applicable). Concomitant medications used to treat SAEs and NDCMCs will be
recorded, as will information on nonstudy vaccinations given since the last
visit. Blood will be taken for immunogenicity assessment.
Participants will return for Visit 4 (335 to 386 days of age). Participants
will be assessed for continued eligibility and information will be collected
from the participant*s parent(s)/legal guardian(s) on SAEs and NDCMCs.
Concomitant medications used to treat SAEs and NDCMCs will be recorded, as will
information on nonstudy vaccinations given since the last visit. Blood will be
taken for immunogenicity assessment prior to vaccination. Dose 3 will be
administered at this visit. Specific concomitant vaccine containing DTaP, HBV,
IPV, and Hib antigens will also be administered.
Specific vaccines containing MMR and varicella antigens are also to be
administered at this visit. The MMR and varicella vaccines are intended to be
given to all participants.
However, in case of circumstances due to local practice/recommendations, some
sites may not administer them to their participants at Dose 3, in which case
MMR and varicella vaccines will be considered nonstudy vaccines. Participants
will be observed for 30 minutes after vaccination and any reactions occurring
during that time will be recorded as AEs. The participant*s parent(s)/legal
guardian(s) will be reissued an e-diary (if applicable). The participant*s
parent(s)/legal guardian(s) will be instructed to collect prompted local
reactions and systemic events occurring 7 days after vaccination. Use of
antipyretic/pain medications will also be prompted for and collected daily in
the e-diary for 7 days after vaccination. The participant*s parent(s)/legal
guardian(s) will be instructed to contact the study staff if the participant
experiences redness or swelling >14 caliper units, severe pain at the 20vPnC or
13vPnC injection site, or fever >40.0°C (>104.0°F) in the 7 days after
vaccination, or has an emergency room visit or hospitalization.
All participants will return for Visit 5 (28 to 42 days after Visit 4).
Information will be collected from the participant*s parent(s)/legal
guardian(s) on AEs, SAEs, NDCMCs, and e-diary follow-up (as needed).
Concomitant medications used to treat SAEs or NDCMCs will be recorded, as will
information on nonstudy vaccinations given since the last visit.
Blood will be taken for immunogenicity assessment. Other licensed nonstudy
vaccines may be administered after the blood draw at this visit.
Intervention
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed
product(s), placebo, or medical device(s) intended to be administered to a
study participant according to the study protocol.
For the purposes of this protocol, the term investigational product may be used
synonymously with study intervention.
Study Intervention(s) Administered
20vPnC is a sterile liquid suspension formulation containing saccharides from
pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B,
18C, 19A, 19F, 22F, 23F,
and 33F individually conjugated to CRM197. The vaccine is formulated to contain
2.2 µg of each saccharide, except for 4.4 µg of 6B, per 0.5-mL dose. The
vaccine contains 5 mM succinate buffer, 150 mM sodium chloride, 0.02%
polysorbate 80, and 125 µg aluminum as aluminum phosphate, per 0.5-mL dose.
13vPnC is a sterile liquid suspension formulation containing saccharides from
pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F
individually conjugated to CRM197. The vaccine is formulated to contain 2.2 µg
of each saccharide, except for 4.4 µg
of 6B, per 0.5-mL dose. The vaccine contains 295 *g succinate buffer, 0.85%
sodium chloride, 100 *g polysorbate 80, and 125 µg aluminum as aluminum
phosphate, per 0.5-mL dose.
The 13vPnC supply is considered representative of Prevnar 13, as it is
manufactured according to the approved Prevnar 13 commercial drug product
process using commercially released vaccine drug substances.
20vPnC and 13vPnC, supplied as syringes, are both white suspensions and have a
matching appearance.
DTaP, HBV, IPV, and Hib vaccine (supplied as a vial and a prefilled syringe) is
a vaccine indicated for active immunization against diphtheria, tetanus,
pertussis, hepatitis B caused by all known subtypes of hepatitis B virus,
poliomyelitis, and Hib infection, respectively. See the investigational product
manual (IP manual) and applicable SRSD.
MMR vaccine (supplied as a vial and prefilled syringe with solvent) is a live
virus vaccine for vaccination against measles (rubeola), mumps, and rubella
(German measles). See the IP manual and applicable SRSD provided.
Varicella vaccine (supplied as a vial and prefilled syringe with solvent) is a
live virus vaccine for vaccination against varicella. See the IP manual and
applicable SRSD.
Investigational product will be supplied by Pfizer as prefilled syringes or
vials. Each syringe/vial will be packaged in a carton with a label and a
tamper-evident seal, and will be labeled as required per country requirement
(refer to the IP manual).
Administration
Participants will receive 1 dose of 20vPnC or 13vPnC at each vaccination visit
(Visits 1, 2, and 4) in accordance with the study*s SoA.
Participants will also receive 1 dose of DTaP, HBV, IPV, and Hib vaccine at
Visits 1, 2, and
4. Participants are also to receive MMR and varicella vaccines at Visit 4 in
accordance with the study*s SoA. The MMR and varicella vaccines are intended to
be given to all participants. However, in case of circumstances due to local
practice/recommendations, some sites may not administer them to their
participants at Dose 3, in which case MMR and varicella vaccines will be
considered nonstudy vaccines. If MMR and varicella vaccines are not given with
Dose 3, and administered based on local practice/recommendations, they are not
to be given during the interval <28 days before Dose 3 through the Visit 5
blood draw after Dose 3.
20vPnC and 13vPnC should be administered intramuscularly by injecting 0.5 mL
into the anterolateral thigh muscle of the left leg at the vaccination visits.
The DTaP, HBV, IPV, and Hib vaccine will be administered concomitantly with
20vPnC or 13vPnC and must be given in a limb other than the site of
administration of 20vPnC or 13vPnC, as appropriate for the age of the child and
the route of administration (ie, intramuscular or subcutaneous).
The MMR and varicella vaccines will be administered concomitantly with 20vPnC
or 13vPnC and must be given in a limb other than the site of administration of
20vPnC or 13vPnC, as appropriate for the age of the child and the route of
administration (ie, intramuscular or subcutaneous).
Standard vaccination practices must be observed and vaccine must not be
injected into blood vessels. Appropriate medication and other supportive
measures for management of an acute hypersensitivity reaction should be
available in accordance with local guidelines for standard immunization
practices.
Administration of investigational products should be performed by an
appropriately qualified, Good Clinical Practice (GCP)-trained, and
vaccine-experienced member of the study staff (eg, physician, nurse,
physician*s assistant, nurse practitioner, pharmacist, or medical assistant) as
allowed by local, state, and institutional guidance.
Investigational product administration details will be recorded on the case
report form (CRF).
Study burden and risks
Please refer to the subject information sheet and the Reference Safety
Information (RSI) in the Investigator's Brochure for a complete overview of the
risks of participation.
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Listed location countries
Age
Inclusion criteria
Section 5.1 in protocol
1. Male or female infants born at >36 weeks of gestation and 2 months of age
(*42 to *112 days) at the time of consent (the day of birth is considered day
of life 1).
2. Participants whose parent(s)/legal guardian(s) are willing and able to
comply with all scheduled visits, treatment plan, and other study procedures.
3. Healthy infants determined by clinical assessment, including medical history
and clinical judgment, to be eligible for the study.
4. Expected to be available for the duration of the study and whose
parents(s)/legal guardian can be contacted by telephone during study
participation.
5. Participants whose parent(s)/legal guardian(s) 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.
Exclusion criteria
Section 5.2 in protocol
1. History of severe adverse reaction associated with a vaccine and/or severe
allergic reaction (eg, anaphylaxis) to any component of investigational product
or any diphtheria toxoid*containing vaccine.
2. Significant neurological disorder or history of seizure including febrile
seizure or significant stable or evolving disorders such as cerebral palsy,
encephalopathy, hydrocephalus, or other significant disorders. Does not include
resolving syndromes due to birth trauma, such as Erb*s palsy and/or
hypotonic-hyporesponsive episodes.
3. Major known congenital malformation or serious chronic disorder
4. History of microbiologically proven invasive disease caused by S pneumonia
5. Known or suspected immunodeficiency or other conditions associated with
immunosuppression, including, but not limited to, immunoglobulin class/subclass
deficiencies, DiGeorge syndrome, generalized malignancy, human immunodeficiency
virus (HIV) infection, leukemia, lymphoma, or organ or bone marrow transplant.
6. Bleeding diathesis or condition associated with prolonged bleeding that
would, in the opinion of the investigator, contraindicate intramuscular
injection.
7. Congenital, functional, or surgical asplenia
8. Other acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation
of study results and, in the judgment of the investigator, would make the
participant inappropriate for entry into this study.
9. Previous vaccination with any licensed or investigational pneumococcal
vaccine, or planned receipt through study participation.
10. Prior receipt of diphtheria, tetanus, pertussis, poliomyelitis, and/or Hib
vaccine
11. Currently receives treatment with immunosuppressive therapy, including
cytotoxic agents or systemic corticosteroids, or planned receipt through the
last blood draw. 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 investigational product administration.
Inhaled/nebulized, intra-articular, intrabursal, or topical (skin, eyes, or
ears) corticosteroids are permitted.
12. Receipt of blood/plasma products or immunoglobulins (including hepatitis B
immunoglobulin) since birth or planned receipt through the last planned blood
draw in the study (Visit 5, 13-month visit).
13. Participation in other studies involving investigational drug(s),
investigational vaccines, or investigational devices within 28 days prior to
study entry and/or during study participation or intrauterine exposure to
investigational vaccines. Participation in purely observational studies is
acceptable.
14. Children or grandchildren who are direct descendants of investigator site
staff members or Pfizer employees who are directly involved in the conduct of
the study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 17980 |
| EudraCT | EUCTR2019-003306-27-NL |
| CCMO | NL74110.000.20 |