A Trial to Assess the Lot Consistency, Safety, Tolerability and Immunogenicity of Bivalent rLP2086 Vaccine When Given to Healthy Subjects Aged ≥10 to <19 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 whether healthy adolescent subjects receiving different lots of vaccine respond in a similar way. 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 3, Randomized, Active-controlled, Observer-blinded Trial To Assess The Lot Consistency, Safety, Tolerability, And Immunogenicity Of A Meningococcal Serogroup B Bivalent Rlp2086 Vaccine In Healthy Subjects Aged >/=10 To <19 Years

Conditions
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Meningococcal Vaccine

Intervention / Treatment
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* Biological: rLP2086
* Biological: rLP2086
* Biological: rLP2086
* Biological: Havrix (HAV)
* Biological: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject aged >=10 and <19 years at the time of enrollment. Healthy subject as determined by medical history, physical examination, and judgment of the investigator. Negative urine pregnancy test for all female subjects. Exclusion Criteria: Previous vaccination with any meningococcal serogroup B vaccine. Subjects who have received prior HAV vaccination. Subjects who are scheduled to receive 1 or more doses of an HPV vaccine as part of a 3-dose series during the period between Visit 1 and 28 days after the second vaccination. Subjects receiving any allergen immunotherapy with a nonlicensed product or receiving allergen immunotherapy with a licensed product and are not on stable maintenance doses. 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 in the United States with terminal complement deficiency are excluded from participation in this study. Significant neurological disorder or history of seizure (excluding simple febrile seizure). Current chronic use of systemic antibiotics. Received any investigational vaccines, drugs, or devices within 28 days before administration of the first study vaccination. Any neuroinflammatory or autoimmune condition, including, but not limited to, transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rLP2086 lot 1<br> | Biological: rLP2086<br>* 0.5 mL dose, given at 0, 2 and 6 months (lot 1)<br>|
| Experimental: rLP2086 lot 2<br> | Biological: rLP2086<br>* 0.5 mL dose, given at 0, 2 and 6 months (lot 2)<br>|
| Experimental: rLP2086 lot 3<br> | Biological: rLP2086<br>* 0.5 mL dose, given at 0, 2 and 6 months (lot 3)<br>|
| Active Comparator: Control<br>Havrix (HAV) and Saline | Biological: Havrix (HAV)<br>* 0.5 mL dose or 1.0 mL dose dependent on age given at month 0 and 6.<br>Biological: Saline<br>* 0.5 mL dose of sterile normal saline for injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With >=4 Fold Rise in Serum Bactericidal Assay Using Human Complement (hSBA) for 4 Primary Strains and Composite Response (hSBA >=Lower Limit of Quantification [LLOQ] for All 4 Primary Strains Combined) for Group 1 | Groups 2 and 3 were included for the Lot consistency analysis for primary strains only (hSBA geometric mean titer). The immunogenicity of two MnB strains in lots 1,2,3 were required to test for lot consistency. These data are presented separately in the other endpoints. The data for all the strains in Lot 1 (Group 1) is sufficient to describe the immunogenicity expected with the vaccine. The analytical plan was included in the protocol and agreement was reach with EMA and FDA. Here, N signifies participants with valid and determinate hSBA titers for given strain at specified time point. | One month after third bivalent rLP2086 vaccination | 
| hSBA Geometric Mean Titers (GMTs) for Each of the 2 Primary Test Strains Measured 1 Month After the Third Vaccination With Bivalent rLP2086 Vaccine |  | One month after third bivalent rLP2086 vaccination | 
| Percentage of Participants Reporting Local Reactions (LRs) Within 7 Days After First Vaccination |  | Within 7 Days after first vaccination | 
| Percentage of Participants Reporting Local Reactions (LRs) Within 7 Days After Second Vaccination |  | Within 7 Days after second vaccination | 
| Percentage of Participants Reporting Local Reactions (LRs) Within 7 Days After Third Vaccination |  | Within 7 Days after third vaccination | 
| Percentage of Participants Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After First Vaccination | Here, N signifies participants with known values reporting specific characteristic. | Within 7 Days after first vaccination | 
| Percentage of Participants Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Second Vaccination | Here, N signifies participants with known values reporting specific characteristic. | Within 7 Days after second vaccination | 
| Percentage of Participants Reporting Systemic Events (SEs) and Antipyretic Use Within 7 Days After Third Vaccination | Here, N signifies participants with known values reporting specific characteristic. | Within 7 Days after third vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Within 30 Days After First Vaccination |  | Within 30 days after first vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Second Vaccination |  | Within 30 days after second vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Third Vaccination |  | Within 30 days after third vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Any Vaccination |  | Within 30 days after any vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) During the Vaccination Phase |  | From the first vaccination up to 1 month after the third vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) During the Follow-Up Phase |  | From 1 month after third vaccination up to 6 months after the third vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event (SAE) Throughout the Study Period |  | From the first vaccination up to 6 month after the third vaccination | 
| Percentage of Participants With at Least 1 Medically Attended AE Within 30 Days After First Vaccination |  | Within 30 days after first vaccination | 
| Percentage of Participants With at Least 1 Medically Attended AE Within 30 Days After Second Vaccination |  | Within 30 days after second vaccination | 
| Percentage of Participants With at Least 1 Medically Attended AE Within 30 Days After Third Vaccination |  | Within 30 days after third vaccination | 
| Percentage of Participants With at Least 1 Medically Attended AE Within 30 Days After Any Vaccination |  | Within 30 days after any vaccination | 
| Percentage of Participants With at Least 1 Medically Attended AE During the Vaccination Phase |  | From the first vaccination up to 1 month after the third vaccination | 
| Percentage of Participants With at Least 1 Medically Attended AE During the Follow-Up Phase |  | From 1 month after third vaccination up to 6 months after the third vaccination | 
| Percentage of Participants With at Least 1 Medically Attended AE Throughout the Study Period |  | From the first vaccination up to 6 month after the third vaccination | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After First Vaccination |  | Within 30 days after first vaccination | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Second Vaccination |  | 30 days after second vaccination | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Third Vaccination |  | Within 30 days after third vaccination | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Any Vaccination |  | Within 30 Days After any Vaccination | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition During the Vaccination Phase |  | From the first vaccination up to 1 month after the third vaccination | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition During the Follow-Up Phase |  | From 1 month after third vaccination up to 6 months after the third vaccination | 
| Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition Throughout the Study Period |  | From the first vaccination up to 6 month after the third vaccination | 
| Percentage of Participants With at Least 1 Adverse Event (AE) WIthin 30 Days After First Vaccination |  | Within 30 days after first vaccination | 
| Percentage of Participants With at Least 1 Adverse Event (AE) Within 30 Days After Second Vaccination |  | Within 30 days after second vaccination | 
| Percentage of Participants With at Least 1 Adverse Event (AE) Within 30 Days After Third Vaccination |  | Within 30 days after third vaccination | 
| Percentage of Participants With at Least 1 Adverse Event Within 30 Days After Any Vaccination |  | Within 30 Days after any vaccination | 
| Percentage of Participants With at Least 1 Adverse Event During the Vaccination Phase |  | From the first vaccination up to 1 month after the third vaccination | 
| Percentage of Participants Reporting at Least 1 Immediate AE After First Vaccination |  | Within 30 minutes after first vaccination | 
| Percentage of Participants Reporting at Least 1 Immediate AE After Second Vaccination |  | Within 30 minutes after second vaccination | 
| Percentage of Participants Reporting at Least 1 Immediate AE After Third Vaccination |  | Within 30 minutes after third vaccination | 
| Number of Days Participant's Missed School or Work Due to AE During the Vaccination Phase |  | From the first vaccination up to 1 month after the third vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With hSBA Titers >=LLOQ for 10 Secondary Strains Before First Vaccination and 1 Month After Third Bivalent rLP2086 Vaccination for Group 1 | Groups 2 and 3 were included for the Lot consistency analysis for primary strains only (hSBA geometric mean titer). The immunogenicity of two MnB strains in lots 1, 2, 3 were required to test for lot consistency. These data are presented separately in the other endpoints. The data for all the strains in Lot 1 (Group 1) is sufficient to describe the immunogenicity expected with the vaccine. The analytical plan was included in the protocol and agreement was reach with EMA and FDA. | Before first vaccination, 1 month after third vaccination | 
| Percentage of Participants With hSBA Titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64, >=1:128 for Each of the 10 Secondary Strains, Before Vaccination 1 and 1 Month After the Third Bivalent rLP2086 Vaccination for Group 1 | Groups 2 and 3 were included for the Lot consistency analysis for primary strains only (hSBA geometric mean titer). The immunogenicity of two MnB strains in lots 1, 2, 3 were required to test for lot consistency. These data are presented separately in the other endpoints. The data for all the strains in Lot 1 (Group 1) is sufficient to describe the immunogenicity expected with the vaccine. The analytical plan was included in the protocol and agreement was reach with EMA and FDA. | Before first vaccination, 1 month after third vaccination (Vac) | 
| hSBA Geometric Mean Titers (GMTs) for Each of the 10 Secondary Strains Before First Vaccination and 1 Month After the Third Bivalent rLP2086 Vaccination for Group 1 | Groups 2 and 3 were included for the Lot consistency analysis for primary strains only (hSBA geometric mean titer). The immunogenicity of two MnB strains in lots 1, 2, 3 were required to test for lot consistency. These data are presented separately in the other endpoints. The data for all the strains in Lot 1 (Group 1) is sufficient to describe the immunogenicity expected with the vaccine. The analytical plan was included in the protocol and agreement was reach with EMA and FDA. | Before first vaccination, 1 month after third vaccination | 
| Percentage of Participants Achieving Composite hSBA Titer >=Lower Limit of Quantitation for All 4 Primary Strains Before First Vaccination and 1 Month After Second Bivalent rLP2086 Vaccination for Group 1 | Groups 2 and 3 were included for the Lot consistency analysis for primary strains only (hSBA geometric mean titer). The immunogenicity of two MnB strains in lots 1, 2 ,3 were required to test for lot consistency. These data are presented separately in the other endpoints. The data for all the strains in Lot 1 (Group 1) is sufficient to describe the immunogenicity expected with the vaccine. The analytical plan was included in the protocol and agreement was reach with EMA and FDA. | Before vaccination 1, 1 Month after Vaccination 2 | 
| Percentage of Participants Achieving at Least a 4-Fold Increase in hSBA Titer for Each of the 4 Primary Strains Before First Vaccination to 1 Month After the Second Bivalent rLP2086 Vaccination for Group 1 | Groups 2 and 3 were included for the Lot consistency analysis for primary strains only (hSBA geometric mean titer). The immunogenicity of two MnB strains in lots 1, 2, 3 were required to test for lot consistency. These data are presented separately in the other endpoints. The data for all the strains in Lot 1 (Group 1) is sufficient to describe the immunogenicity expected with the vaccine. The analytical plan was included in the protocol and agreement was reach with EMA and FDA. | One month after second Bivalent rLP2086 vaccination | 
| Percentage of Participants Achieving at Least a 4-Fold Increase in hSBA Titer for 2 Primary Strains Before First Vaccination to 1 Month After the Second and Third Bivalent rLP2086 Vaccination |  | One month after second, third vaccination | 
| hSBA Geometric Mean Titers (GMTs) for 4 Primary Test Strains and for 2 Primary Test Strains and Before First Vaccination and 1 Month After the Second Bivalent rLP2086 Vaccination |  | Before vaccination (Vac) 1, 1 Month after Vac 2 | 
| Percentage of Participants With hSBA Titers >=LLOQ for 4 Primary Test Strains Before First Vaccination, 1 Month After Second and Third Bivalent rLP2086 Vaccination |  | Before Vaccination (Vac) 1, 1 Month after Vac 2, 3 | 
| Percentage of Participants With hSBA Titers >=1:4,>=1:8,>=1:16,>=1:32,>=1:64,>=1:128 for Primary Test Strains Before First Vaccination, 1 Month After Second and Third Bivalent rLP2086 Vaccination | Results for PMB80[A22] 1:16, PMB2001[A56] 1:8, PMB2948[B24] 1:8 and PMB2707[B44] 1:8 are reported under secondary outcome measure 'Percentage of Participants With hSBA Titers >=LLOQ for 4 Primary Test Strains Before First Vaccination, 1 Month After Second and Third Bivalent rLP2086 Vaccination. | Before Vaccination (Vac) 1, 1 Month after Vac 2, 3 | 
| Percentage of Participants Achieving at Least a 3-Fold Increase in hSBA Titer for 4 Primary Test Strains and for Primary Test Starins Before First Vaccination to 1 Month After Third Bivalent rLP2086 Vaccination |  | One month after third bivalent rLP2086 vaccination | 
| Percentage of Participants Achieving at Least a 2-Fold Increase in hSBA Titer for 4 Primary Test Strains and for 2 Primary Test Starins Before First Vaccination to 1 Month After the Third Bivalent rLP2086 Vaccination |  | One month after third bivalent rLP2086 vaccination (Vac) |