| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Inflammation of the brain and infection of the blood |
|
| 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 | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028911 |
| E.1.2 | Term | Neisseria meningitidis infection NOS |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10032810 |
| E.1.2 | Term | Other specified meningococcal infections |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10070124 |
| E.1.2 | Term | Neisseria meningitidis test positive |
| E.1.2 | System Organ Class | 100000004848 |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
•To demonstrate non-inferiority of MenACWY-TT co-ad with a viral vaccine compared to MenACWY-TT alone with respect to GMTs for A, C, W-135 and Y.
•To demonstrate the non-inferiority of a viral vaccine co-ad with MenACWY-TT compared to a viral vaccine alone in terms of HPV GMTs.
•To demonstrate non-inferiority of MenACWY-TT co-ad with a viral vaccine and Boostrix compared to MenACWY-TT alone with respect to GMTs for A, C, W-135 and Y.
•To demonstrate non-inferiority of a viral vaccine co-ad with MenACWY-TT and Boostrix compared to a viral vaccine co-administered with Boostrix in terms of HPV GMTs.
•To demonstrate non-inferiority of Boostrix co-ad with MenACWY-TT and a viral vaccine compared to Boostrix co-administered with a viral vaccine in terms of anti-D and anti-T concentrations.
•To demonstrate non-inferiority of Boostrix co-ad with MenACWY-TT and a viral vaccine compared to Boostrix co-administered with a viral vaccine with respect to GMCs to pertussis antigens.
|
|
| E.2.2 | Secondary objectives of the trial |
immunogenicity of subjects in the ACWYHPV, ACWY-TT and Co-ad groups in terms of subjects with rSBA titres and vaccine response.
immunogenicity of the TT carrier protein in the ACWY-TT group in terms of subjects with anti-T concentrations and GMCs.
immunogenicity of a viral vaccine in subjects in the ACWYHPV, HPV, Co-ad, ACWY-TT and Tdap groups with respect to subjects with titres ≥8 EL.U/mL for anti-HPV16 and ≥7 EL.U/mL for anti-HPV18.
immunogenicity of subjects in the ACWY-TT group with respect to HPV16 and HPV18 GMTs.
immunogenicity of all subjects with respect to seroconversion rates of anti-HPV titers.
the booster responses to PT, FHA and PRN in the Co-ad and Tdap groups.
the immunogenicity of Boostrix in the Co-ad and Tdap groups in terms of anti-D and anti-T concentrations and GMCs, and anti-PT, FHA and PRN concentrations.
Solicited local and general symptoms
Unsolicited adverse events.
SAEs and NOCI(s) and pIMDs.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects and subjects’ parent(s)/Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
A female between, and including, 9 and 25 years of age at the time of the first vaccination.
Written informed consent obtained from parents/guardian of the subject and written informed assent obtained from the subject if the subject is less than legal age, or written informed consent obtained from the subject if the subject has achieved legal age. The legal age will be determined according to local regulations in each participating country.
Healthy subjects as established by medical history and clinical examination before entering into the study.
Female subjects of non-childbearing potential may be enrolled in the study.
–Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
Female subjects of childbearing potential may be enrolled in the study, if the subject:
-has practiced adequate contraception for 30 days prior to vaccination, and
-has a negative pregnancy test on the day of vaccination, and
-has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
|
|
| E.4 | Principal exclusion criteria |
Child in care
Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will be ≥10 mg/day prednisone or equivalent. Inhaled and topical steroids are allowed.
Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after each study dose of vaccine(s), with the exception of licensed inactivated influenza vaccine.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational product or a non-investigational vaccine/product.
Previous vaccination with a meningococcal polysaccharide or conjugate vaccine within the last 10 years.
History of meningococcal disease since birth.
History of serious allergic reaction following any other DTP-containing vaccine or any component of the study vaccines.
History of encephalopathy within seven days of administration of a previous pertussis antigen-containing vaccine that is not attributable to another identifiable cause.
Persons who experienced an Arthus-type hypersensitivity reaction following a prior dose of tetanus-toxoid containing vaccine should not receive Boostrix unless at least 10 years have elapsed since the last dose of tetanus-toxoid containing vaccine.
Previous vaccination with a tetanus-toxoid containing vaccine within the previous five years.
Temperature of ≥ 40.5°C (105°F) within 48 hours of receipt of a previous dose of DTP vaccine (diphtheria-tetanus-whole cell pertussis [DTPw] and/or diphtheria-tetanus-acellular pertussis [DTaP]), not due to another identifiable cause.
Collapse or shock-like state within 48 hours of receipt of a previous dose of DTP vaccine.
Seizures with or without fever within three days of a previous dose of DTP vaccine.
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and history directed physical examination.
A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.
History of any allergic disease/reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
Progressive neurologic disorder, unstable neurologic conditions, uncontrolled epilepsy or progressive encephalopathy.
History of any neurologic disorders or seizures. A history of ADHD or depression or a history of a single, simple febrile seizure does not exclude a subject.
Major congenital defects or serious chronic illness.
Previous history of Guillain-Barré Syndrome.
Bleeding disorders, such as hemophilia or thrombocytopenia, or subjects on anti-coagulant therapy.
Acute disease and/or fever at the time of enrolment.
Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
Previous vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
Previous administration of MPL or AS04 adjuvant.
History of chronic alcohol consumption and/or drug abuse.
Pregnant or lactating female.
A subject planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose.
Subjects must be at least three months post-pregnancy and not breastfeeding to enter the study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY GMTs in the ACWY-TT, ACWYHPV and Co-ad groups.
Anti-HPV16 and anti-HPV18 GMTs in the HPV, ACWYHPV, Co-ad and Tdap groups.
anti-D and anti-T concentrations ≥1.0 IU/mL in the Co-ad and Tdap groups
anti-PT, anti-FHA and anti-PRN GMCs in the Co-ad and Tdap groups
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
One month after vaccination with MenACWY-TT.
One month after the 3rd dose of a licensed viral vaccine.
One month after vaccination with Boostrix.
|
|
| E.5.2 | Secondary end point(s) |
rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY antibody titres ≥1:8, ≥1:128 and vaccine response one month post-vaccination in all subjects of the ACWYHPV, ACWY-TT and Co-ad groups.
Anti-T concentrations ≥0.1 IU/mL, ≥1.0 IU/mL and GMCs in the ACWY-TT group.
•Anti-HPV16 titres ≥8 EL.U/mL and anti-HPV18 titres ≥7 EL.U/mL in the ACWYHPV, HPV, Co-ad, ACWY-TT and Tdap groups.
•Anti-HPV16 and anti-HPV18 seroconversion rates in the ACWYHPV, ACWY-TT, HPV, Co-ad and Tdap groups post-dose 3.
•Anti-HPV16 and anti-HPV18 GMTs in the ACWY-TT group.
•Booster responses for PT, FHA and PRN in the Co-ad and Tdap groups
•Anti-D and anti-T concentrations ≥0.1 IU/mL and GMCs in the Co-ad and Tdap groups
•Anti-PT, anti-FHA and anti-PRN concentrations ≥5 EL.U/mL in the Co-ad and Tdap groups
Occurrence of solicited local and general symptoms after vaccination with MenACWY-TT in the ACWYHPV, ACWY-TT and Co-ad groups, after the first dose of a licensed viral vaccine in the ACWY-TT, HPV and Tdap groups and after vaccination with Boostrix in the Co-ad and Tdap groups.
Occurrence of unsolicited adverse events after vaccination with MenACWY-TT, Boostrix or the first dose of a licensed viral vaccine in all groups according to the Medical Dictionary for Regulatory Activities (MedDRA).
Occurrence of serious adverse events in all groups after the first vaccination.
New onset of chronic illness(es) (NOCIs) (e.g., autoimmune disorders, asthma, type I diabetes and allergies) and pIMDs in all groups.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Prior to and one month after vaccination with MenACWY-TT.
Prior to and one month after vaccination with MenACWY-TT.
Prior to the first dose of a licensed viral vaccine and one month after the 3rd dose of a licensed viral vaccine.
Prior to and one month after vaccination with Boostrix
During Days 0-6 following vaccination with MenACWY-TT, Boostrix or the first dose of a licensed viral vaccine.
During Days 0-30 following vaccination with MenACWY-TT, Boostrix or the first dose of a licensed viral vaccine.
Up to 8 months after the first vaccination.
Up to 8 months after the first vaccination.
|
|
| 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 | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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 |
| Dominican Republic |
| Brazil |
| Thailand |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 14 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 14 |
Print
