Phase 2, Observer-Blind, Placebo-Controlled, Randomized, Multi-Center Extension Study to Evaluate the Safety and Immunogenicity of a Booster Dose of a MenABCWY Vaccine Administered 24 Months Following the Primary Series to Adolescents and Young Adults Who Participated in V102_03 (NCT01272180)

Study Overview
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Brief Summary
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The purpose of this extension study is to evaluate the immunogenicity and safety of a booster dose of a MenABCWY vaccine, administered 24 months after completion of the primary vaccination series, in subjects who previously received the same vaccine formulation in study V102_03 (NCT01272180) (Groups I and II). Antibody persistence at 24 and 36 months after the primary vaccination and 12 months after the booster dose will also be evaluated in these subjects. In addition, safety and immunogenicity of two investigational MenABCWY vaccine formulations (either a MenABCWY+ OMV or a MenABCWY+¼ OMV) will be assessed in subjects who previously received two doses of MenB vaccine (Group III) or one dose of Menveo vaccine (Group IV). These subjects will be followed for safety and immunogenicity for 12 months after vaccination in study V102_03E1.

Official Title
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Phase 2, Observer-Blind, Placebo-Controlled, Randomized, Multi-Center Extension Study to Evaluate the Safety and Immunogenicity of a Booster Dose of a MenABCWY Vaccine Administered 24 Months Following the Primary Series to Adolescents and Young Adults Who Participated in V102_03 (NCT01272180)

Conditions
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Meningococcal Disease

Intervention / Treatment
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* Biological: MenABCWY+OMV
* Biological: MenABCWY+¼OMV
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females that received both vaccinations and completed the Study Termination visit in the primary study, V102_03 (NCT01272180); Individuals or the individual's parents or legal guardian who have given written consent after the nature of the study has been explained according to local regulatory requirements; Individuals who have given written assent as required by local regulations after the nature of the study has been explained to them according to local regulatory requirements; Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator; Individuals and/or or the individual's parents or legal guardian who can comply with study procedures and are available for follow-up. Exclusion Criteria: History of any meningococcal vaccine administration other than the vaccination administered in the primary study, V102_03 (NCT01272180); Current or previous, confirmed or suspected disease caused by N. meningitidis; Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment; History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component; All sexually active females that have not used an acceptable contraceptive method(s) for at least 2 months prior to study entry. Acceptable birth control methods are defined as one or more of the following: Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring) Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse Intrauterine device (IUD) Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the subject's study entry; Sexually active females that refuse to use to an acceptable contraceptive method through to 3 weeks following the study vaccination; Female subjects with a positive pregnancy test prior to the study vaccine being administered; Nursing (breastfeeding) mothers; Individuals with a history of illness or with an ongoing illness that, in the opinion of the investigator, may pose additional risk to the subject if he/she participates in the study; Any serious, chronic, or progressive disease (e.g., neoplasm, diabetes, cardiac disease, hepatic disease, progressive neurological disease or seizure disorder; autoimmune disease, HIV infection or AIDS, blood dyscrasias, bleeding diathesis, signs of cardiac or renal failure, or severe malnutrition); Subjects who required chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the study vaccination. (For corticosteroids, this means prednisone, or equivalent, ≥ 20mg/day. Inhaled and topical steroids are allowed). Receipt of blood, blood products and/or plasma derivatives, or a parenteral immunoglobulin preparation within the previous 90 days; Individuals participating in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study; Administration or planned administration, of any vaccine not foreseen by the study protocol within 30 days prior study vaccination, and up to 30 days after the vaccination (with the exception of any licensed influenza vaccine which may be administered >14 days preceding or >14 days following the study vaccination); Individuals who study personnel or immediate family members of study personnel including brother, sister, child, parent, or the spouse. Individuals who have experienced moderate or severe acute infection and/or fever (defined as temperature ≥ 38°C) within 3 days prior to enrolment. Who have received systemic antibiotic treatment within 7 days prior to enrollment.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 25 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: Ia: MenABCWY+OMV<br>Investigational | Biological: MenABCWY+OMV<br>* Vaccine contains rMenB (50 µg per antigen) with 25 µg of OMV (a full dose) plus the fully lyophilized MenACWY vaccine<br>|
| Placebo Comparator: Ib: Placebo<br>Saline | Biological: Placebo<br>* Saline solution for injection (0.5mL)<br>|
| Experimental: IIa: MenABCWY+¼OMV<br>Investigational | Biological: MenABCWY+¼OMV<br>* Vaccine contains rMenB (50 µg per antigen) with 6.25 µg OMV (1/4 dose) plus the fully lyophilized MenACWY vaccine<br>|
| Placebo Comparator: IIb: Placebo<br>Saline | Biological: Placebo<br>* Saline solution for injection (0.5mL)<br>|
| Experimental: IIIa: MenABCWY+OMV<br>Investigational | Biological: MenABCWY+OMV<br>* Vaccine contains rMenB (50 µg per antigen) with 25 µg of OMV (a full dose) plus the fully lyophilized MenACWY vaccine<br>|
| Experimental: IIIb: MenABCWY+¼OMV<br>Investigational | Biological: MenABCWY+¼OMV<br>* Vaccine contains rMenB (50 µg per antigen) with 6.25 µg OMV (1/4 dose) plus the fully lyophilized MenACWY vaccine<br>|
| Experimental: IVa: MenABCWY+OMV<br>Investigational | Biological: MenABCWY+OMV<br>* Vaccine contains rMenB (50 µg per antigen) with 25 µg of OMV (a full dose) plus the fully lyophilized MenACWY vaccine<br>|
| Experimental: IVb: MenABCWY+¼OMV<br>Investigational | Biological: MenABCWY+¼OMV<br>* Vaccine contains rMenB (50 µg per antigen) with 6.25 µg OMV (1/4 dose) plus the fully lyophilized MenACWY vaccine<br>|
| Placebo Comparator: IVc: Placebo<br>Saline | Biological: Placebo<br>* Saline solution for injection (0.5mL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Percentages of Subjects With HT-hSBA (High-throughput Human Serum Bactericidal Assay) Seroresponse Against N. Meningitidis Serogroups A, C, W and Y. | Percentages of subjects having HT-hSBA seroresponse against N. meningitidis serogroups A, C, W and Y, following administration of a booster dose of MenABCWY, in the present study, in subjects who previously received the same MenABCWY vaccine formulation in study V102_03 (NCT01272180). Seroresponse to N. meningitidis serogroups A, C, W and Y is defined as: for subjects with a pre-vaccination HT-hSBA titer < 1:4, a post-vaccination hSBA titer ≥ 1:8; for subjects with a pre-vaccination hSBA titer ≥ 1:4, an increase in hSBA titer of at least four times the pre-vaccination titer. | Day 30 | 
| 2. Percentage of Subjects With HT-hSBA Titers ≥ 1:5 Against Strains of N. Meningitidis Serogroups B. | Percentage of subjects reporting HT-hSBA titers ≥ 1:5 against strains of N. meningitidis serogroups B at baseline (Day 1) and one month (Day 30) following administration of a booster dose of MenABCWY, in the present study, in subjects who previously received the same MenABCWY vaccine formulation in study V102_03 (NCT01272180). | Day 1 and Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3. Percentage of Subjects With HT-hSBA Titer ≥ 1:8 to N. Meningitides Serogroups A, C, W, Y. | Percentage of subjects with HT-hSBA titer ≥ 1:8 in serogroups A, C, W, Y against N. meningitides assessed prior to the administration of MenABCWY booster vaccination or placebo. Pre vaccination is 24 months after completion of the primary vaccination series, in subjects who previously received the same vaccine formulation in study V102_03 (NCT01272180). | Day 1 (Pre vaccination) | 
| 4. Percentage of Subjects With HT-hSBA Titer ≥ 1:5 to N. Meningitidis Strains of Serogroup B. | Percentage of subjects with HT-hSBA titer ≥ 1:5 against N. meningitidis strains of serogroup B assessed prior to the administration of MenABCWY booster vaccination or placebo. Pre vaccination is 24 months after completion of the primary vaccination series, in subjects who previously received the same vaccine formulation in study V102_03 (NCT01272180). | Day 1 (Pre vaccination) | 
| 5. The HT-hSBA Geometric Mean Titers (GMTs) Against N. Meningitidis Serogroups A, C, W,Y. | The HT-hSBA GMTs against N. meningitidis serogroup A, C, W, Y prior the administration of MenABCWY booster vaccination or placebo. Pre vaccination is 24 months after completion of the primary vaccination series, in subjects who previously received the same vaccine formulation in study V102_03 (NCT01272180). | Day 1 (Pre-vaccination) | 
| 6. The HT-hSBA GMTs Against N. Meningitidis Strains of Serogroup B. | The HT-hSBA GMTs against N. meningitidis strains of serogroup B prior the administration of MenABCWY booster vaccination or placebo. Pre vaccination is 24 months after completion of the primary vaccination series, in subjects who previously received the same vaccine formulation in study V102_03 (NCT01272180). | Day 1 (Pre-vaccination) | 
| 7. The HT-hSBA GMTs Against N. Meningitidis Serogroups A, C, W, Y. | The HT-hSBA GMTs against N. meningitidis serogroup A, C, W, Y at Day 1 and Day 30 (one month) after the administration of MenABCWY booster vaccination or placebo. | Day 1 and Day 30 | 
| 8. The HT-hSBA GMTs Against N. Meningitidis Strains of Serogroups B. | The HT-hSBA GMTs against N. meningitidis strains of serogroups B at Day 1 and Day 30 (one month) after the administration of MenABCWY booster vaccination or placebo. | Day 1 and Day 30 | 
| 9. Percentage of Subjects With Four-fold Rise in HT-hSBA Titers Against N. Meningitidis Serogroup B Strains. | Percentage of subjects with four-fold rise in HT-hSBA titers against N. meningitidis serogroup B strains, from Day 1 (baseline) to Day 30 (one month) after the administration of MenABCWY booster vaccination or placebo. Four-fold rise is defined as follows: for subjects with a pre-vaccination titer < 1:2, a post-titer of ≥ 1:8; for subjects with a pre-vaccination titer ≥ 1:2 at least a four-fold increase. | Day 1 and Day 30 | 
| 10. Percentage of Subjects With HT-hSBA Titer ≥ 1:8 Against N. Meningitidis Serogroups A,C,W,Y. | Percentage of subjects with HT-hSBA titer ≥ 1:8 to N. meningitidis serogroups A,C,W,Y at Day 1 and Day 30 (one month) after the administration of a booster dose of MenABCWY vaccine or placebo in this study, versus baseline. | Day 1 and Day 30 | 
| 11. Percentage of Subjects With HT-hSBA Titer ≥ 1:5 Against N. Meningitidis Serogroup B Strains. | Percentage of subjects with HT-hSBA titer ≥ 1:5 to N. meningitidis serogroup B strains at Day 1 and Day 30 (one month) after the administration of a booster dose of MenABCWY vaccine or placebo in this study, versus baseline. | Day 1 and Day 30 | 
| 12. Percentage of Subjects With Seroresponse to N. Meningitidis Serogroups A, C, W and Y, at Day 30 After Booster Vaccination in This Study. | Percentage of subjects with seroresponse to N. meningitidis serogroup A, C, W and Y, at Day 30 after the administration of a booster dose of MenABCWY vaccine or placebo in this study, versus baseline. | Day 30 | 
| 13. Percentage of Subjects With HT-hSBA Titer ≥ 1:8 to N. Meningitidis Serogroups A, C, W,Y. | Percentage of subjects with HT-hSBA titer ≥ 1:8 against N. meningitidis serogroups A, C, W, Y, at 24 and 36 months after the primary vaccination. | Day 1 and Day 365 | 
| 14. Percentage of Subjects With HT-hSBA Titer ≥ 1:5 to N. Meningitidis Strains of Serogroup B | Percentage of subjects with HT-hSBA titer ≥ 1:5 against N. meningitidis strains of serogroup B, at 24 and 36 months after the primary vaccination. | Day 1, Day 30 and Day 365 | 
| 15. Percentage of Subjects With Four-fold Rise in HT-hSBA Titers Against N. Meningitidis Serogroup B Strains. | Percentage of subjects with four-fold rise in HT-hSBA titers against N. meningitidis serogroup B strains, at 24 and 36 months after the primary vaccination. Four-fold rise is defined as follows: for subjects with a pre-vaccination titer < 1:2, a post-titer of ≥ 1:8; for subjects with a pre-vaccination titer ≥ 1:2 at least a four-fold increase. | Day 1, Day 30 and Day 365 | 
| 16. The HT-hSBA GMTs Against N. Meningitidis Serogroups A, C, W, Y. | The HT-hSBA GMTs against N. meningitidis serogroup A, C, W, Y, at 24 and 36 months after the primary vaccination. | Day 1 and Day 365 | 
| 17. The HT-hSBA GMTs Against N. Meningitidis Strains of Serogroups B. | The HT-hSBA GMTs against N. meningitidis strains of serogroups B, at 24 and 36 months after the primary vaccination. | Day 1 and Day 365 | 
| 18. Percentage of Subjects With HT-hSBA Titer ≥ 1:8 to N. Meningitidis Serogroups A, C, W,Y. | Percentage of subjects with HT-hSBA titer ≥ 1:8 against N. meningitidis serogroups A, C, W, Y at Day 1, Day 30 (one month) and Day 365 (12 months) after the administration of MenABCWY booster vaccination. | Day 1, Day 30 and Day 365 | 
| 19. Percentage of Subjects With HT-hSBA Titer ≥ 1:5 to N. Meningitidis Strains of Serogroup B. | Percentage of subjects with HT-hSBA titer ≥ 1:5 against N. meningitides strains of serogroups B at Day 1, Day 30 (one month) and Day 365 (12 months) after the administration of MenABCWY booster vaccination. | Day 1, Day 30 and Day 365 | 
| 20. The HT-hSBA GMTs Against Neisseria Meningitidis Serogroups A, C, W,Y and Strains of Serogroups B. | The HT-hSBA GMTs against Neisseria meningitidis serogroup A, C, W, Y and strains of serogroups B at Day 1, Day 30 (one month) and Day 365 (12 months) after the administration of MenABCWY booster vaccination. | Day 1, Day 30 and Day 365 | 
| 21. The HT-hSBA GMTs Against Neisseria Meningitidis Strains of Serogroups B. | The HT-hSBA GMTs against Neisseria meningitidis strains of serogroups B at Day 1, Day 30 (one month) and Day 365 (12 months) after the administration of MenABCWY booster vaccination. | Day 1, Day 30 and Day 365 | 
| 22. Percentage of Subjects With HT-hSBA Titer ≥ 1:8 to N. Meningitidis Serogroups A,C,W,Y at 12 Months After Booster Vaccination. | Percentage of subjects with HT-hSBA titer ≥ 1:8 to N. meningitidis serogroups A,C,W,Y at Day 1, Day 30 (one month) and Day 365 (12 months) after the administration of MenABCWY booster vaccination in this study. | Day 1, Day 30 and Day 365 | 
| 23. Number of Subjects With Solicited Local and Systemic Adverse Events Following Booster Vaccination in This Study. | Number of subjects reporting solicited local and systemic adverse events after receiving a booster dose of MenABCWY vaccine or placebo. the below reported events are Erythema- Injection site erythema, Induration- Injection site induration, Pain-injection site pain, Arthralgia, Chills, Fatigue, Headache, Loss of Appetite, Myalgia, Nausea, Rash, Fever, Prevention- Prevention of Pain and/or Fever, Treatment- Treatment of Pain and/or Fever and Analgesic/Antipyr.: use of Analgesic/Antipyretics in pain and fever. | From day 1 (6 hours) through day 7 after any vaccination | 
| 24. Number of Subjects With Unsolicited (Any AEs and Possibly Related AEs) Following Booster Vaccination in This Study. | Number of subjects reporting unsolicited AEs (any AEs and at least possibly related AEs) after receiving a booster dose of MenABCWY vaccine or placebo from Day 1 to Day 30. Analysis was done on the Unsolicited Safety Set. All subjects in the exposed population who provided information about post-vaccination AEs or safety records at Day 30. | Day 1 through Day 30 | 
| 25. Number of Subjects With Unsolicited Adverse Events Following Booster Vaccination in This Study. | Number of subjects reporting any serious unsolicited AEs (SAEs), possibly related SAEs, medically attended AEs, unsolicited AEs leading to withdrawal and deaths after receiving a booster dose of MenABCWY vaccine or placebo, are reported for the entire study period. | Day 1 to Day 365 | 
| 26. Number of Subjects With Unsolicited Adverse Leading to New Onset Chronic Disease (NOCD) Before Study Vaccination. | Number of subjects reporting New Onset Chronic Disease (NOCD),from the end of the primary parental study V102_03 (NCT01272180) up to Day 1 visit in V102_03E1 study, is reported. (Any NOCD AEs: NOCD V102_03 (NCT01272180) vs. NOCD- Day 1, V102_03E1) | From primary parent study completion up to Day 1 in this study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal, Booster, MenABCWY, Menveo, Vaccine Adolescents, Immune Response, N. Meningitidis