| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| This study will evaluate the safety and immunogenicity of a booster dose of MenABCWY vaccine; either MenABCWY+OMV or MenABCWY+1/4OMV, administered to adolescent and young adults who previously received the same MenABCWY formulation in the primary study V102_03. This extension study will also assess the safety and immunogenicity non-inferiority of a single dose of MenABCWY in subject who received two doses of Bexsero or a single dose of Menveo in the primary study. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Immunogenicity and safety of a booster dose of an investigational vaccine against N. meningitidis serogroups A, B, C, W and Y, administered to subjects previously vaccinated with the same vaccine. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10027202 |
| E.1.2 | Term | Meningitis bacterial |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1.To evaluate the immune response against meningococcus serogroups A, C, W and Y as measured by percentage of subjects having seroresponse at Day 30 following administration of a booster dose of MenABCWY in subjects who previously received the same vaccine formulation in study V102_03. 2.To evaluate the immune response against strains of serogroup B as measured by percentage of subjects having hSBA titers ≥ 1:5 at Day 30 following administration of a booster dose of MenABCWY in subjects who previously received the same vaccine formulation in study V102_03.
Seroresponse to N. meningitidis serogroups A, C, W and Y is defined as:
▫ For subjects with a pre-vaccination 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.
Safety Objectives:
1.To evaluate the safety and reactogenicity.
2.To assess safety in terms of New Onset of Chronic Diseases (NOCD). |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the immune response against N. meningitidis serogroups A, C, W and Y and strains of serogroup B at Day 30 following the booster vaccination with MenABCWY vaccine in subjects who previously participated in V102_03.
2. To evaluate the antibody persistence against N. meningitidis serogroups A, C, W and Y and strains of serogroup B at 24 and 36 months after the primary vaccination series in subjects who previously participated in V102_03.
3. To evaluate the antibody persistence against N. meningitidis serogroups A, C, W and Y and strains of serogroup B 12 months following the booster vaccination with MenABCWY vaccine in subjects who previously participated in V102_03.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Males and females that received both vaccinations and completed the Study Termination visit in the primary study, V102_03;
2. 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;
3. 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;
4. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator;
5. Individuals and/or or the individual’s parents or legal guardian who can comply with study procedures and are available for follow-up. |
|
| E.4 | Principal exclusion criteria |
1. History of any meningococcal vaccine administration other than the vaccination administered in the primary study, V102_03;
2. Current or previous, confirmed or suspected disease caused by N. meningitidis;
3. Household contact with and/or intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 60 days of enrollment;
4. History of severe allergic reactions after previous vaccinations or hypersensitivity to
any vaccine component;
5. 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:
a. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring)
b. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse
c. Intrauterine device (IUD)
d. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the subject’s study entry;
6. Sexually active females that refuse to use to an “acceptable contraceptive method”
through to 3 weeks following the study vaccination;
7. Female subjects with a positive pregnancy test prior to the study vaccine being
administered;
8. Nursing (breastfeeding) mothers;
9. 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;
10. 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);
11. 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).
12. Receipt of blood, blood products and/or plasma derivatives, or a parenteral immunoglobulin preparation within the previous 90 days;
13. 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;
14. 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);
15. Individuals who study personnel or immediate family members of study personnel including brother, sister, child, parent, or the spouse.
16. Individuals who have experienced moderate or severe acute infection and/or feve (defined as temperature 38°C) within 3 days prior to enrolment.
17. Who have received systemic antibiotic treatment within 7 days prior to enrolment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
In subjects that previously received a MenABCWY vaccine in the V102_03 study (Groups I and II), the following endpoints will be assessed at Day 30 following administration of a MenABCWY vaccination or placebo:
1. Percentage of subjects with seroresponse to N. meningitidis serogroups A, C, W and Y
2. Percentage of subjects with hSBA titer ≥1:5 to N. meningitidis serogroup B strains
Notes:
“Pre vaccination titer” is defined as hSBA titer on Day 1 in study V102_03E1.
Seroresponse to N. meningitidis serogroups A, C, W and Y is defined as:
▫ For subjects with a pre-vaccination 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.
Safety Endpoints:
▫ Study Termination in V102_03 – Visit Day 1 (V102_03E1):
- Relevant medical history conditions and diagnosis, as well as NOCD will be summarized and coded by using MedDRA preferred terms
▫ 30 minutes, 6 hours – Day 3, Day 4 – Day 7, 6 hours – Day 7:
- Any solicited local adverse event (pain, induration and erythema)
- Any solicited systemic adverse event (chills, nausea, fatigue, myalgia, arthralgia, loss of appetite, headache, rash, body temperature/fever)
▫ Visit Day 1- Visit Day 30:
- Any unsolicited adverse event and the severity
▫ During the entire study period (Visits Day 1 to Day 365):
- Serious adverse events, New Onset of Chronic Diseases (NOCD), medically attended adverse events and adverse events leading to withdrawal
▫ From completion of the primary study (V102_03) up to Visit Day 1 in study
V102_03E1
- New Onset of Chronic Disease |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary:
At Day 30 following administration of a booster MenABCWY vaccination or placebo for subjects previously vaccinated with one of the MenABCWY vaccine formulations;
Safety:
Study termination in V102_03-Visti Day 1; 30 minutes, 6 hours – Day 3, Day 4 – Day 7, 6 hours – Day 7; Visit Day 1- Visit Day 30; During the entire study period (Visits Day 1 to Day 365); From completion of the primary study (V102_03) up to Visit Day 1 in study V102_03E1
|
|
| E.5.2 | Secondary end point(s) |
In all subjects the following endpoints will be assessed prior to administration of a
booster MenABCWY vaccination or placebo:
1. Percentage of subjects with hSBA titer ≥1:8 to N. meningitidis serogroups A, C, W and Y
2. Percentage of subjects with hSBA titer ≥1:5 s to N. meningitidis serogroup B strains
3. hSBA GMTs against N. meningitidis serogroups A, C, W and Y and strains of serogroup B
In all subjects the following endpoints will be assessed 30 days following administration of a booster MenABCWY vaccination or placebo:
1. Percentage of subjects with hSBA titer ≥1:8 and GMTs to N. meningitidis serogroups A, C, W and Y
2. Percentage of subjects with four-fold rise(3) and GMTs to N. meningitidis serogroup B strains
3. hSBA GMTs against N. meningitidis serogroups A, C, W and Y and strains of serogroup B
In all subjects the following endpoints will be assessed 365 days (12 months) following administration of a MenABCWY booster vaccination or placebo:
1. Percentage of subjects with seroresponse(2) and with hSBA titer ≥1:8 against N meningitidis serogroups A, C, W and Y
2. Percentage of subjects with hSBA titer ≥1:5, and with four-fold rise(3) against N meningitidis serogroup B strains
3. hSBA GMTs against N. meningitidis serogroups A, C, W and Y and strains of serogroup B
In subjects who received MenACWY (Menveo) or rMenB+OMV (Bexsero) vaccines in V102_03 study (Groups III and IV) the following endpoints will be assessed 30 days following administration of a MenABCWY vaccination or placebo:
1. Percentage of subjects with seroresponse(2) to N meningitidis serogroups A, C, W and Y
2. Percentage of subjects with hSBA titer ≥1:5 to N meningitidis serogroups B strains
Notes:
(1)“Pre vaccination titer” is defined as hSBA titer on Day 1 in study V102_03E1.
(2) Seroresponse to N. meningitidis serogroups A, C, W and Y is defined as:
▫ For subjects with a pre-vaccination 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.
(3) 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 4-fold increase |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Prior to administration of a booster MenABCWY vaccination or placebo;
- 30 days prior to administration of a booster MenABCWY vaccination or placebo;
- 365 days (12 months) following administration of a booster MenABCWY vaccination or placebo. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 9 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of trial is defined as reported in the protocol, version 4, section 3.9
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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