E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Juvenile Idiopathic Arthritis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059176 |
E.1.2 | Term | Juvenile idiopathic arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 study the safety of measles, mumps, rubella (MMR) booster vaccination in Juvenile Idiopathic Arthritis (JIA) patients by measuring JIA disease activity. The standard registrated MMR vaccine currently used in the Netherlands National Vaccination Program will be used. We will also measure the incidence of clinically overt measles, mumps or rubella infections in the JIA patients to test safety.
The next primary objective is to evaluate the efficacy of the MMR booster vaccination in the JIA patient population by measuring protective immunity responses before and after MMR vaccination. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to study immune regulatory mechanisms induced by MMR vaccination. It will be evaluated whether MMR booster vaccination is capable of inducing protective regulatory immune responses, such as an increase of T regulatory cells. To construct proper immunoassays, five healthy controls will be included prior to analysis of patient samples. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- all subtypes of Juvenile Idiopathic Arthritis (JIA) patients according to ILAR criteria
- ages 4 - 9 (this is 2 years after initial MMR and before the scheduled booster, usually given at age 9)
- five healthy controls (18-65 years)
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E.4 | Principal exclusion criteria |
- Use of Infliximab (Remicade, anti-TNF alpha therapy).
- Primary immunodeficiency
- Fever less than 48 hour prior to vaccination (here the moment of vaccination will be postponed for 1 month)
- Evidence of viral or bacterial infection less than 48hours prior to vaccination (here the moment of vaccination will be postponed for 1 month)
- Methylprednisolon pulse therapy less than 1 month prior to vaccination (in these cases, the moment of vaccination will be postponed for 1 month)
for healthy controls:
-serious adverse events to previous MMR vaccination
-Use of immunosuppressive drugs
-Primary immunodeficiency
-Fever less than 48 hour prior to vaccination (vaccination will be postponed)
-Evidence of viral or bacterial infection less than 48hours prior to vaccination (vaccination will be postponed)
-Methylprednisolon pulse therapy less than 1 month prior to vaccination (vaccination will be postponed)
-Pregnancy
-Lactation
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety of MMR booster vaccination, according to: JIA disease activity parameters defined by the internationally validated core set criteria, from which the Juvenile Arthritis Disease Activity Score (JADAS-27) will be calculated.
The core set criteria consist of:
- Physician’s Global Assessment (PGA) of disease activity, on a 10-cm visual analogue scale (VAS)
- Number of joints with limited range of motion (LOM), defined a loss of at least 5° in any articular movement with respect to the normal amplitude(37).
- Number of joints with active arthritis, defined by the presence of swelling or limitation of movement accompanied by pain, tenderness or both
- Patient/parent global assessment of overall well being, on a 10-cm VAS
- Physical functionality score, measured using a cross-cultural-adapted Childhood Health Assessment questionnaire (CHAQ) on a 0-3 scale
- Erythrocyte sedimentation rate (ESR) in mm/h or C-reactive protein (CRP) in mg/l.
from these parameters, a Disease Activity Score (DAS) can be calculated.
2) The efficacy of MMR booster vaccination, defined by:
- specific anti measles, rubella and mumps antibody levels (measured by Enzyme linked Immunosorbent Assays; ELISA)
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E.5.2 | Secondary end point(s) |
Secondary outcomes for MMR booster safety are:
A) Number of disease flares in the 12 months after MMR vaccination. A disease flare will be defined as a worsening of ≥40% in ≥2 criteria without a simultaneous improvement of ≥30% in ≥2 of the remaining core set criteria.
B) Medication use (especially MTX, steroids, etanercept)
C) Incidence of measles, mumps or rubella infection.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
no MMR booster vaccination during the study (i.e between 4-8 years instead of 9 yrs of age). |
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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.8.5.1 | Number of sites anticipated in the EEA | 0 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |