Pneumococcal VaccinesPhase 3NCT05721456
Evaluation of the Non-Inferiority of a 12-Valent Pneumococcal Conjugate Vaccine in Healthy Children in Brazil.
A Phase 3 study testing 12-Valent Pneumococcal Conjugate Vaccine in people with Pneumococcal Vaccines, run by Maria de Lourdes de Sousa Maia, MD.
Trial summary
The purpose of this phase III study is to demonstrate immunologic non-inferiority in terms of proportion of individuals with antibody concentration ≥0.2 µg/mL (by modified 22F-inhibition enzyme-linked immunosorbent assay, ELISA) or in terms of ELISA geometric mean concentrations (GMC) of serotype-specific IgG, of… Read more about this study
- Who is it for?
- Ages 2 to 4 monthsHealthy volunteers can take part
- Conditions the study is for
- Pneumococcal Vaccines
- What is being tested?
- 12-Valent Pneumococcal Conjugate Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,400 participants
- Where
- No sites listed yet
- Study dates
- 28 Aug 2023to 28 Jan 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 4 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Male or female subjects, 6-12 weeks of age, inclusive, at the time of the first vaccination.
- Healthy subjects as established by medical history and clinical examination before entering into the study.
- Subjects who the investigator believes that parent(s)/ Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol, including:
- willing to provide name, address, and telephone number for contact if necessary (e.g., in case of missing a scheduled visit)
- available for follow-up throughout the study period
- capable to complete the forms for registration of signs and symptoms at home.
- Parent(s)/LAR(s) are able to understand and sign the informed consent form.
Who cannot join
- Preterm infants (gestation <36 weeks) or with low birth weight (<2000g).
- Use of any investigational or non-registered product other than the study vaccines and allowed co-administered vaccines as outlined in section 3.4.9. during the entire study period. Any other vaccine administration must be discussed and approved by the medical monitor.
- Medical history of culture- or PCR-confirmed invasive disease caused by S. pneumoniae.
- Coagulation problems.
- Chronic administration (more than 14 days in total) of corticosteroids, immunosuppressants or other immune-modifying drugs (except palivizumab) since birth or planned use during the study.
- Administration of immunoglobulins and/or blood products since birth or planned use during the study period.
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- Participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine.
- Major congenital defects or serious chronic illness.
- History of any seizures or any neurological disease
- Acute disease and/or fever (axillary temperature ≥38ºC) at the time of enrolment.
- Previous vaccination with any pneumococcal vaccine.
- Infants born of woman who received any pneumococcal vaccine during pregnancy.
About this study
Official title: A Phase 3, Randomized, Partially-Blind, Clinical Trial to Evaluate the Non-Inferiority of a 12-Valent Pneumococcal Conjugate Vaccine in Healthy Children in Brazil, Compared to 10- and 13-Valent Pneumococcal Conjugate Vaccines
The purpose of this phase III study is to demonstrate immunologic non-inferiority in terms of proportion of individuals with antibody concentration ≥0.2 µg/mL (by modified 22F-inhibition enzyme-linked immunosorbent assay, ELISA) or in terms of ELISA geometric mean concentrations (GMC) of serotype-specific IgG, of 12-valent pneumococcal polysaccharide conjugate vaccine (12Pn-PD-DiT-CRM, hereby indicated as PCV12), containing the serotypes 1, 4, 5, 6B, 7F, 9V, 14, and 23F conjugated with non-typeable Haemophilus influenzae protein D, 19F conjugated with TD, 18C conjugated with TT, and 6A and 19A conjugated with CRM197, and to assess its safety in the population of infants vaccinated from 2 months of age with a primary regimen of 2 or 3 doses plus a booster administered at one year of life.
Read the detailed description
The purpose of this phase III study is to demonstrate immunologic non-inferiority in terms of proportion of individuals with antibody concentration ≥0.2 µg/mL (by modified 22F-inhibition enzyme-linked immunosorbent assay, ELISA) or in terms of ELISA geometric mean concentrations (GMC) of serotype-specific IgG, of 12-valent pneumococcal polysaccharide conjugate vaccine (12Pn-PD-DiT-CRM, hereby indicated as PCV12), containing the serotypes 1, 4, 5, 6B, 7F, 9V, 14, and 23F conjugated with non-typeable Haemophilus influenzae protein D, 19F conjugated with TD, 18C conjugated with TT, and 6A and 19A conjugated with CRM197, and to assess its safety in the population of infants vaccinated from 2 months of age with a primary regimen of 2 or 3 doses plus a booster administered at one year of life. Hence, this study will provide non-inferiority evidence for possible approval of a new pneumococcal vaccine in Brazil and its eventual inclusion in the national immunization program (PNI). PCV12 will be produced in national facilities, after transfer of technology to Bio-Manguinhos/Fiocruz, thus ensuring continuous provision to the public healthcare system (SUS).
This study is designed to demonstrate the immunologic non-inferiority of the PCV12 for each one of the 12 vaccine pneumococcal serotypes, when compared to the licensed vaccines GSK Synflorix® (PCV10) and Pfizer's/Wyeth's Prevenar 13® (PCV13). PCV10 will be used for the comparison of the immune response to the 10 common serotypes. PCV13 or the least immunogenic serotype of PCV10 will be used for the comparison of the immune response to the two additional pneumococcal serotypes 19A and/or 6A conjugated to CRM197.
The non-inferiority of PCV12 will be evaluated in the two schedules recommended in Brazil, the 2+1 scheme (followed by PNI) or the 3+1 scheme (the reference schedule when evaluating new vaccines).
- Conditions
- Pneumococcal Vaccines
- Being tested
- 12-Valent Pneumococcal Conjugate Vaccine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
12-Valent Pneumococcal Conjugate VaccineBiological
Also called PCV12
PCV12 group 1: 550 subjects receiving the 12-valent pneumococcal polysaccharide conjugate vaccine (12Pn-PD-DiT-CRM), defined as PCV12 in this protocol
| Study group | Role | What they receive |
|---|---|---|
| PCV10 (Synflorix®) | Active comparator | Not described Receives: Biological: 12-Valent Pneumococcal Conjugate Vaccine |
| PCV13 (Prevenar13®) | Active comparator | Not described Receives: Biological: 12-Valent Pneumococcal Conjugate Vaccine |
| 12-Valent Pneumococcal Conjugate Vaccine | Experimental | Not described Receives: Biological: 12-Valent Pneumococcal Conjugate Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The immunological non-inferiority of pneumococcal vaccine 12 in relation to pneumococcal vaccine 10 and 13.
Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥0.20 µg/mL after primary vaccination.Geometric mean concentrations of serotype-specific pneumococcal IgG antibody after primary vaccination.
Measured: 5 months
Secondary outcomes (4)
Functional Antibody Response
Opsonophagocytic activity (OPA) for antibodies against each of the pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F will be measured by a killing-assay using a HL 60 cell line (37) or using a multiplex assay. The results will be presented as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions, as geometric mean titers (GMTs). The defined cut-off of the assay is an opsonic titer of 8, and percentage of children with titers ≥8 will also be presented for each serotype.
Paired samples of the same individual will also be tested, however, without breaking the blinding relative to the time of collection (pre or post vaccination) and the type of vaccine received (experimental or comparators).
Measured: 17 months
Immunogenicity after booster
Pneumococcal serotype specific total IgG antibodies (antibodies to 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) will each be measured by 22F-inhibition ELISA). The antibody concentration will be determined by logistic log comparison of the ELISA curves with a standard reference serum 89-SF or SP007 available from the US Food and Drug Administration for which concentration of IgG to the 12 serotypes are known in μg/mL . The cut-off of the assay is 0.05 μg/mL. For each group, immune responses to each serotype will be expressed as antibody GMCs and the percentage of children with IgG concentrations ≥0.2 μg/mL that is equivalent to concentrations of ≥0.35 μg/mL measured by the non-22F ELISA, of the World Health Organization reference laboratory.
Samples of the same individual will be tested in a paired manner but without breaking the blinding relative to the time of collection (pre or post vaccination) and the type of vaccine received (experimental or comparators).
Measured: 17 months
Safety and reactogenicity vaccination and booster vaccination.
Proportion of subjects with any and Grade 3 solicited local adverse event (AE) within 7 days after each vaccination dose.
- Proportion of subjects with any and Grade 3 solicited systemic AE, within 7 days after each vaccination dose.
Solicited systemic AEs include drowsiness, irritability/agitation, loss of appetite and fever (axillary temperature ≥ 38°C).
- Proportion of subjects with any solicited or unsolicited AEs after each vaccination dose. on.
- Proportion of subjects with any serious adverse event (SAE) after last dose of primary vaccination.
- Proportion of subjects with any SAE after booster vaccination.
Measured: 18 months
Immunogenicity, safety and reactogenicity co-administered vaccines
Due to the restriction of collecting larger volumes of blood in young children, this analysis will be restricted to a subsample of 120 study subjects (60 per schedule, 20:20:20 per vaccination group), randomly selected and without breaking study blinding.The evaluation of antitetanic and anti-diphteric antibodies, and of IgG specific for purified capsular polysaccharides from Neisseria meningitidis serogroup C, present in the volunteer sera will be performed in Bio-Manguinhos/Fiocruz, assessed by the immunoenzymatic technique (ELISA) and expressed in international units per milliliter of serum (IU/mL). Paired samples of the same individual will also be tested, however, without breaking the blinding relative to the time of collection (pre or post vaccination) and the type of vaccine received (experimental or comparators).
Measured: 17 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2023
- Study start28 Aug 2023 (estimated)
- Primary completion28 Apr 2024 (estimated)
- Study completion28 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pneumococcal VaccinesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maria de Lourdes de Sousa Maia, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Maria de Lourdes de Sousa Maia, MD, The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05721456
- Sponsor's protocol ID
- Protocol ASCLIN 002/2022
- Status last verified
- Jan 2023
- First submitted
- 23 Nov 2022
- Last updated
- 10 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Partially-Blind, Clinical Trial to Evaluate the Non-Inferiority of a 12-Valent Pneumococcal Conjugate Vaccine in Healthy Children in Brazil, Compared to 10- and 13-Valent Pneumococcal Conjugate Vaccines
- ClinicalTrials.gov ID
- NCT05721456
- Acronym / sponsor ID
- Protocol ASCLIN 002/2022
- Conditions
- Pneumococcal Vaccines
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,400 participants (estimated)
- Lead sponsor
- Maria de Lourdes de Sousa Maia, MDUniversity, hospital or other
- Study start
- 28 Aug 2023 (estimated)
- Primary completion
- 28 Apr 2024 (estimated)
- Study completion
- 28 Jan 2025 (estimated)
- First posted
- 10 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this phase III study is to demonstrate immunologic non-inferiority in terms of proportion of individuals with antibody concentration ≥0.2 µg/mL (by modified 22F-inhibition enzyme-linked immunosorbent assay, ELISA) or in terms of ELISA geometric mean concentrations (GMC) of serotype-specific IgG, of 12-valent pneumococcal polysaccharide conjugate vaccine (12Pn-PD-DiT-CRM, hereby indicated as PCV12), containing the serotypes 1, 4, 5, 6B, 7F, 9V, 14, and 23F conjugated with non-typeable Haemophilus influenzae protein D, 19F conjugated with TD, 18C conjugated with TT, and 6A and 19A conjugated with CRM197, and to assess its safety in the population of infants vaccinated from 2 months of age with a primary regimen of 2 or 3 doses plus a booster administered at one year of life.
Detailed description
The purpose of this phase III study is to demonstrate immunologic non-inferiority in terms of proportion of individuals with antibody concentration ≥0.2 µg/mL (by modified 22F-inhibition enzyme-linked immunosorbent assay, ELISA) or in terms of ELISA geometric mean concentrations (GMC) of serotype-specific IgG, of 12-valent pneumococcal polysaccharide conjugate vaccine (12Pn-PD-DiT-CRM, hereby indicated as PCV12), containing the serotypes 1, 4, 5, 6B, 7F, 9V, 14, and 23F conjugated with non-typeable Haemophilus influenzae protein D, 19F conjugated with TD, 18C conjugated with TT, and 6A and 19A conjugated with CRM197, and to assess its safety in the population of infants vaccinated from 2 months of age with a primary regimen of 2 or 3 doses plus a booster administered at one year of life. Hence, this study will provide non-inferiority evidence for possible approval of a new pneumococcal vaccine in Brazil and its eventual inclusion in the national immunization program (PNI). PCV12 will be produced in national facilities, after transfer of technology to Bio-Manguinhos/Fiocruz, thus ensuring continuous provision to the public healthcare system (SUS).
This study is designed to demonstrate the immunologic non-inferiority of the PCV12 for each one of the 12 vaccine pneumococcal serotypes, when compared to the licensed vaccines GSK Synflorix® (PCV10) and Pfizer's/Wyeth's Prevenar 13® (PCV13). PCV10 will be used for the comparison of the immune response to the 10 common serotypes. PCV13 or the least immunogenic serotype of PCV10 will be used for the comparison of the immune response to the two additional pneumococcal serotypes 19A and/or 6A conjugated to CRM197.
The non-inferiority of PCV12 will be evaluated in the two schedules recommended in Brazil, the 2+1 scheme (followed by PNI) or the 3+1 scheme (the reference schedule when evaluating new vaccines).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PCV10 (Synflorix®) | Active comparator | Biological: 12-Valent Pneumococcal Conjugate Vaccine |
| PCV13 (Prevenar13®) | Active comparator | Biological: 12-Valent Pneumococcal Conjugate Vaccine |
| 12-Valent Pneumococcal Conjugate Vaccine | Experimental | Biological: 12-Valent Pneumococcal Conjugate Vaccine |
Who may qualify
- Ages
- 2 to 4 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Male or female subjects, 6-12 weeks of age, inclusive, at the time of the first vaccination.
- Healthy subjects as established by medical history and clinical examination before entering into the study.
- Subjects who the investigator believes that parent(s)/ Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol, including:
- Parent(s)/LAR(s) are able to understand and sign the informed consent form.
Key exclusion criteria (14 listed)
- Preterm infants (gestation <36 weeks) or with low birth weight (<2000g).
- Use of any investigational or non-registered product other than the study vaccines and allowed co-administered vaccines as outlined in section 3.4.9. during the entire study period. Any other vaccine administration must be discussed and approved by the medical monitor.
- Medical history of culture- or PCR-confirmed invasive disease caused by S. pneumoniae.
- Coagulation problems.
- Chronic administration (more than 14 days in total) of corticosteroids, immunosuppressants or other immune-modifying drugs (except palivizumab) since birth or planned use during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 12-Valent Pneumococcal Conjugate VaccineAlso: PCV12PCV12 group 1: 550 subjects receiving the 12-valent pneumococcal polysaccharide conjugate vaccine (12Pn-PD-DiT-CRM), defined as PCV12 in this protocol | Biological | 12-Valent Pneumococcal Conjugate Vaccine, PCV10 (Synflorix®), PCV13 (Prevenar13®) |
Primary outcome
The immunological non-inferiority of pneumococcal vaccine 12 in relation to pneumococcal vaccine 10 and 13.
Time frame: 5 months
Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥0.20 µg/mL after primary vaccination.Geometric mean concentrations of serotype-specific pneumococcal IgG antibody after primary vaccination.
4 secondary outcomes
Functional Antibody Response
Time frame: 17 months
Immunogenicity after booster
Time frame: 17 months
Safety and reactogenicity vaccination and booster vaccination.
Time frame: 18 months
Immunogenicity, safety and reactogenicity co-administered vaccines
Time frame: 17 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 12-Valent Pneumococcal Conjugate Vaccine in people with Pneumococcal Vaccines, run by Maria de Lourdes de Sousa Maia, MD.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The immunological non-inferiority of pneumococcal vaccine 12 in relation to pneumococcal vaccine 10 and 13. (time frame: 5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2023.