A Study to Describe the Immunogenicity, Safety, and Tolerability of Neisseria Meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine (Bivalent rLP2086) in Healthy Subjects Aged ≥24 Months to <10 Years

Study Overview
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Brief Summary
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This study is looking at a new vaccine that might prevent meningococcal disease, and will study the immune response elicited by this vaccine when given to healthy young children. The study will also look at the safety of the new vaccine as well as how it is tolerated.

Official Title
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A Phase 2, Randomized, Controlled, Observer-blinded Study To Describe The Immunogenicity, Safety, And Tolerability Of Neisseria Meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine (Bivalent Rlp2086) In Healthy Subjects Aged >/= 24 Months To <10 Years

Conditions
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MENINGOCOCCAL INFECTION

Intervention / Treatment
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* Biological: Bivalent rLP2086 Vaccine
* Biological: Licensed pediatric hepatits A vaccine
* Other: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject's parent(s)/legal guardian has been informed of all pertinent aspects of the study. Parent(s)/legal guardian and subject who are willing and able to comply with scheduled visits, vaccine regimen, laboratory tests, and other study procedures. Male or female subjects aged ≥24 months and <10 years at time of randomization, stratified equally by age (≥24 months to <4 years or ≥4 years to <10 years). Subject is available for the entire study period and subject's parent(s)/legal guardian can be reached by telephone. Healthy subject as determined by medical history, physical examination, and judgment of the investigator. Subject must have received all vaccinations in the relevant national immunization program (NIP) for their age group. Male and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. Negative urine pregnancy test for all female subjects who are biologically capable of having children. Exclusion Criteria: Previous vaccination with any meningococcal serogroup B vaccine. Subjects who have received prior HAV vaccination. Contraindication to vaccination with any HAV vaccine or known latex allergy. Subjects receiving any allergen immunotherapy with a nonlicensed product or subjects receiving allergen immunotherapy with a licensed product and who are not on stable maintenance doses. A previous anaphylactic reaction to any vaccine or vaccine-related component. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection. A known or suspected defect of the immune system that would prevent an immune response to the vaccine, such as subjects with congenital or acquired defects in B-cell function, those receiving chronic systemic (oral, intravenous, or intramuscular) corticosteroid therapy, or those receiving immunosuppressive therapy. Subjects with terminal complement deficiency may be included. Additional details will be provided in the study reference manual (SRM). History of microbiologically proven disease caused by N meningitidis or Neisseria gonorrhoeae. Significant neurological disorder or history of seizure (excluding simple febrile seizure). Receipt of any blood products, including immunoglobulin, within 6 months before the first study vaccination. Current chronic use of systemic antibiotics. Participation in other studies involving investigational product(s)/device(s) (Phases 1-4) within 28 days before administration of the first study vaccination. Participation in purely observational studies is acceptable. Any neuroinflammatory or autoimmune condition, including but not limited to transverse myelitis, uveitis, optic neuritis, and multiple sclerosis. Other severe 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 subject inappropriate for entry into this study. Pregnant female subjects, breastfeeding female subjects, male subjects with partners who are currently pregnant, or male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study. Subjects who are children of investigational site staff members directly involved in the conduct of the study and their family members, subjects who are children of site staff members otherwise supervised by the investigator, or subjects who are children of Pfizer employees directly involved in the conduct of the study.

Ages Eligible for Study
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Minimum Age: 24 Months
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bivalent rLP2086<br>Bivalent rLP2086 (containing 60 μg each of a purified subfamily A and subfamily B rLP2086 protein, adsorbed to aluminum in a sterile buffered isotonic suspension) in a 0.5-mL dose for injection. | Biological: Bivalent rLP2086 Vaccine<br>* 1 dose of 120 μg of bivalent rLP2086 by intramuscular injection at Months 0, 2, and 6 into the upper deltoid muscle of the arm.<br>|
| Other: Licensed pediatric hepatitis A vaccine<br> | Biological: Licensed pediatric hepatits A vaccine<br>* 1 0.5 mL dose by intramuscular injection at Months 0 and 6 into the upper deltoid muscle of the arm.<br>Other: Normal Saline<br>* Sterile saline solution for injection (0.85% sodium chloride) in a 0.5 mL dose at Month 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titers >= Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Neisseria Meningitidis Serogroup B (MnB) Test Strains 1 Month After Vaccination 3 | Percentage of participants achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95 percent (%) confidence interval (CIs). LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44). | 1 month after Vaccination 3 | 
| Percentage of Participants Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 1 | Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity) and severe (prevented daily activity). Redness and swelling were graded as: mild (0.5-2.0 centimeter [cm]), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). | Within 7 Days after Vaccination 1 | 
| Percentage of Participants Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 2 | Local reactions included pain at injection site, swelling and redness collected by using an e-diary. Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity) and severe (prevented daily activity). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). | Within 7 Days after Vaccination 2 | 
| Percentage of Participants Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 3 | Local reactions included pain at injection site, swelling and redness collected by using an e-diary. Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity) and severe (prevented daily activity). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). | Within 7 Days after Vaccination 3 | 
| Percentage of Participants Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 1 | Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, >39.5 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevented daily activity). | Within 7 Days after Vaccination 1 | 
| Percentage of Participants Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 2 | Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, >39.5 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevented daily activity). | Within 7 Days after Vaccination 2 | 
| Percentage of Participants Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 3 | Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, >39.5 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevented daily activity). | Within 7 Days after Vaccination 3 | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 1 | SAE was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. | Within 30 Days after Vaccination 1 | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 2 | SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. | Within 30 Days after Vaccination 2 | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 3 | SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. | Within 30 Days after Vaccination 3 | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Any Vaccination | SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. | Within 30 Days after any vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) During the Vaccination Phase | SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. | From the Vaccination 1 up to 1 month after Vaccination 3 | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) During the Follow-up Phase | SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. | From 1 month after Vaccination 3 up to 6 months after Vaccination 3 | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Throughout the Study | SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. | From Vaccination 1 up to 6 months after Vaccination 3 | 
| Percentage of Participants With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 1 | A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. | Within 30 Days after Vaccination 1 | 
| Percentage of Participants With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 2 | A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. | Within 30 Days after Vaccination 2 | 
| Percentage of Participants With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 3 | A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. | Within 30 Days after Vaccination 3 | 
| Percentage of Participants With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Any Vaccination | A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. | Within 30 Days after any vaccination | 
| Percentage of Participants With at Least 1 Medically Attended Adverse Event (AE) During the Vaccination Phase | A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. | From the Vaccination 1 up to 1 month after the Vaccination 3 | 
| Percentage of Participants With at Least 1 Medically Attended Adverse Event (AE) During the Follow-up Phase | A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. | From 1 month after Vaccination 3 up to 6 months after the Vaccination 3 | 
| Percentage of Participants With at Least 1 Medically Attended Adverse Event (AE) Throughout the Study | A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. | From the Vaccination 1 up to 6 months after the Vaccination 3 | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 1 | A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. | Within 30 Days after Vaccination 1 | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 2 | A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. | Within 30 Days after Vaccination 2 | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 3 | A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. | Within 30 Days after Vaccination 3 | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Any Vaccination | A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. | Within 30 Days after any vaccination | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition During the Vaccination Phase | A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. | From the Vaccination 1 up to 1 month after the Vaccination 3 | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition During the Follow-up Phase | A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. | From 1 month after Vaccination 3 up to 6 months after the Vaccination 3 | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Throughout the Study | A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. | From the Vaccination 1 up to 6 months after the Vaccination 3 | 
| Percentage of Participants With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 1 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Within 30 Days after Vaccination 1 | 
| Percentage of Participants With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 2 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Within 30 Days after Vaccination 2 | 
| Percentage of Participants With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 3 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Within 30 Days after Vaccination 3 | 
| Percentage of Participants With at Least 1 Adverse Event (AE) Within 30 Days After Any Vaccination | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Within 30 Days after any vaccination | 
| Percentage of Participants With at Least 1 Adverse Event (AE) During the Vaccination Phase | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | From the Vaccination 1 up to 1 month after the Vaccination 3 | 
| Percentage of Participants With at Least 1 Immediate Adverse Event (AE) After Vaccination 1 | Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. | Within 30 minutes after Vaccination 1 | 
| Percentage of Participants With at Least 1 Immediate Adverse Event (AE) After Vaccination 2 | Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. | Within 30 minutes after Vaccination 2 | 
| Percentage of Participants With at Least 1 Immediate Adverse Event (AE) After Vaccination 3 | Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. | Within 30 minutes after Vaccination 3 | 
| Number of Days Participant's Missed School Due to Adverse Event (AE) During the Vaccination Phase |  | From the Vaccination 1 up to 1 month after the Vaccination 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Aged >=24 Months to <10 Years With hSBA Titer >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 3 | Percentage of participants achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95% CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44). | 1 month after Vaccination 3 | 
| Percentage of Participants With hSBA Titer >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 2 and 6 Months After Vaccination 3 | Percentage of participants achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95% CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44). | 1 month after Vaccination 2 and 6 months after Vaccination 3 | 
| Percentage of Participants With Serum Bactericidal Assay Using hSBA Titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64 and >=1:128 for Each of the 4 Primary Test Strains |  | Before Vaccination 1, 1 month after Vaccination 2, 1 month after Vaccination 3 and 6 months after Vaccination 3 | 
| Serum Bactericidal Assay Using Human Complement (hSBA) Geometric Mean Titers (GMTs) for Each of the 4 Primary Test Strains |  | Before Vaccination 1, 1 month after Vaccination 2, 1 month after Vaccination 3 and 6 months after Vaccination 3 |