Pneumonia, Bacterial, Pneumococcal Infections, Pneumonia, Pneumococcal
Conditions
Keywords
Pneumonia, Pneumococcal, Infections, Streptococcal Infections, Pneumonia
Brief summary
This is a Phase 2 clinical study evaluating AFX3772 in healthy infants for the prevention of pneumococcal disease. The purpose of this study is to determine the safety, tolerability, and immunogenicity of three different formulations of AFX3772 compared with Prevnar 13 (PCV13) and Prevnar 20 (PCV20). Part 1 is the dose-escalation lead-in portion of the study, in which infants at each dose level are randomized 3:1 in sequential cohorts to receive increasing doses of AFX3772 or PCV13. In Part 2, infants are randomized to receive either one of two dose levels of AFX3772 or PCV20. On 31 October 2024, the study was placed on partial clinical hold by the U.S. Food and Drug Administration. The hold was not related to safety concerns in participants who had already received the study vaccines. As a result, enrollment was paused and no further doses of the investigational pneumococcal vaccine were administered. Participants who were already enrolled transitioned to the standard of care pneumococcal vaccine to complete their scheduled visits through post-dose 3 and subsequently completed study follow-up.
Interventions
BIOLOGICALAFX3772
AFX3772 administered intramuscularly.
BIOLOGICALPrevnar 13
PCV13 administered intramuscularly.
BIOLOGICALPrevnar 20
PCV 20 administered intramuscularly.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
42 Days to 90 Days
Healthy volunteers
Yes
Inclusion criteria
1. Participant has an LAR who understands study procedures, alternative treatments and risks involved in the study and who voluntarily agrees to participate by giving informed consent. 2. Participant is a full-term (≥37 weeks gestation at birth) infant approximately 2 months of age (42 to 90 days, inclusive) at time of obtaining the informed consent. 3. Participant is healthy based on the clinical judgment of the investigator following review of medical history and physical examination.
Exclusion criteria
1. Participant had prior administration of any pneumococcal vaccine. 2. Participant has a known or suspected hypersensitivity to AFX3772, PCV13, PCV20 or any components of the formulations used. 3. Participant has a known or suspected immunodeficiency (including autoimmune disease) or other conditions associated with immunosuppression that may require immunosuppressive drugs including but not limited to HIV infection, malignancy or organ or bone marrow transplant. a. In addition, the participant's biological mother has known HIV infection or known to be hepatitis B surface antigen positive. 4. Participant has any clinically significant allergic condition or history (including anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to the first vaccination for primary immunization series. 5. Participant has functional asplenia. 6. Participant has medical history of epilepsy or febrile convulsion. 7. Participant weighed \<2000 g at birth. 8. Participant has known neurological or cognitive behavioral disorders including clinically significant developmental disorder and related disorders. 9. Participant has any active malignancy or history of malignancy. 10. Participant has a history of microbiologically proven invasive disease caused by S. pneumoniae. 11. Participant has cochlear implant or cerebrospinal fluid leakage. 12. Has received other licensed non-live vaccines within the 14 days or a licensed live virus vaccine within the 30 days prior to receipt of study vaccine. 13. Participant has received immunoglobulins. Note: This does not include monoclonal antibodies, such as palivizumab or nirsevimab. 14. Participant has a bleeding diathesis or condition associated with prolonged bleeding that would contraindicate intramuscular injection. 15. Participant has received systemic corticosteroids (equivalent of \>2 mg/kg total daily dose of prednisone or \>20 mg/day for persons weighing \>10 kg) for a period of more than 14 days and has not completed the treatment for at least 30 days before study vaccine. Topical, ophthalmic, and inhaled steroids are allowed. 16. Participant has febrile illness (rectal temperature ≥38.1°C \[100.5°F\] or axillary temperature ≥37.8°C \[100.0°F\]) in Part 1 and Part 2 prior to the effective date of protocol amendment 4. After protocol amendment 4 becomes effective, febrile illness is defined as rectal temperature ≥38.0°C \[100.4°F\] or axillary temperature ≥37.5°C (99.1°F) in Part 2. Upon resolution of symptoms, participant can be rescreened. 17. Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening. 18. Participant has any condition which, in the investigator's opinion, makes the participant unsuitable for study participation. 19. LARs that are study personnel or their immediate dependents, family, or household members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Any Solicited Injection Site Adverse Events (AEs) After First Dose | Day 1 to Day 7 post dose 1 | The assessed solicited injection site events were pain/tenderness, redness/erythema and swelling/induration. Any = occurrence of the event regardless of the intensity grade. |
| Number of Participants Reporting Any Solicited Injection Site AEs After Second Dose | Day 1 to Day 7 post dose 2 | — |
| Number of Participants Reporting Any Solicited Injection Site AEs After Third Dose | Day 1 to Day 7 post dose 3 | — |
| Number of Participants Reporting Any Solicited Systemic Events After First Dose | Day 1 to Day 7 post dose 1 | The assessed solicited systemic events are irritability, fever, appetite loss, increased sleep, and decrease in sleep. Any = occurrence of the event regardless of the intensity grade. |
| Number of Participants Reporting Any Solicited Systemic Events After Second Dose | Day 1 to Day 7 post dose 2 | — |
| Number of Participants Reporting Any Solicited Systemic Events After Third Dose | Day 1 to Day 7 post dose 3 | — |
| Number of Participants Reporting Any Unsolicited AEs | Within 30 days post each dose (at 2, 4, and 6 months of age as part of primary vaccination series) | An unsolicited AE was defined as any adverse event that was not actively solicited through the participant eDiary and was reported by the participant's legally authorized representative (LAR) or identified by site personnel. Unsolicited AEs included both serious and non-serious AEs. Any = occurrence of the event regardless of the intensity grade. |
| Number of Participants Reporting Any Serious Adverse Events (SAEs) | Day 1 through 6 months post dose 3 | An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires in patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity. Medical or scientific judgment will be exercised by the investigator in deciding whether SAE reporting is appropriate in other situations such as significant medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With a Pneumococcal Serotype-specific Immunoglobulin G (IgG) Concentration of >= 0.35 μg/mL | 30 days post-dose 2 and 3 | Immunogenicity data has not been presented since no participants completed the planned 3+1 vaccination regimen with the investigational vaccine and instead received standard-of-care pneumococcal vaccination. |
| Geometric Mean Concentration (GMC) for Serotype-specific IgG | 30 days post-dose 2 and 3 | Immunogenicity data has not been presented since no participants completed the planned 3+1 vaccination regimen with the investigational vaccine and instead received standard-of-care pneumococcal vaccination. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
A total of 388 participants were enrolled in the study, including 130 in Part 1 and 258 in Part 2. Of these, 380 participants were randomized, and 376 participants received at least 1 dose of study vaccination.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous Part 1 | 64.6 Days STANDARD_DEVIATION 5.89 |
| Age, Continuous Part 2 | 65.2 Days STANDARD_DEVIATION 8.85 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 10 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Mutiple | 30 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 7 Participants |
| Race/Ethnicity, Customized White or Caucasian | 267 Participants |
| Sex/Gender, Customized Female | 15 Participants |
| Sex/Gender, Customized Male | 12 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 | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 32 | 0 / 30 | 0 / 29 | 1 / 83 | 0 / 86 | 0 / 86 |
| other Total, other adverse events | 30 / 30 | 30 / 32 | 28 / 30 | 29 / 29 | 74 / 83 | 77 / 86 | 78 / 86 |
| serious Total, serious adverse events | 3 / 30 | 1 / 32 | 2 / 30 | 2 / 29 | 7 / 83 | 6 / 86 | 1 / 86 |
Outcome results
None listed