E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Extended oligoarticular juvenile idiopathic arthritis (JIA) Enthesitis-related arthritis (ERA) Psoriatic arthritis (PsA)
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003246 |
E.1.2 | Term | Arthritis |
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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 |
Part 1: To assess the clinical benefit of etanercept in subjects with extended oligoarticular JIA, ERA, or PsA. Part 2: To assess the long-term safety of etnaercept in subjects with extended oligoarticular JIA, ERA, or PsA.
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E.2.2 | Secondary objectives of the trial |
Part 1: To assess the effect of etanercept on safety and physical functioning in subjects with extended oligoarticular JIA, ERA, or PsA. Part 2: To assess the effect of etanercept on clinical benefit and physical functioning in subjects with extended oligoarticular JIA, ERA, or PsA.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects must have met ILAR criteria for diagnosis of 1 of the following JIA subtypes (see Attachment 1 for ILAR criteria) before the screening visit and must be within the specified age range at the time of the screening visit:
- extended oligoarticular JIA between the ages of 2 and 17 years. - ERA between the ages of 12 and 17 years. - PsA between the ages of 12 and 17 years.
2. At both the screening and baseline visits, the following criteria must be met for the relevant JIA subtype: - Extended oligoarticular JIA: - >= 2 active peripheral joints (swollen or, in the absence of swelling, limited range of motion accompanied by either pain or tenderness) - A history of intolerance or an unsatisfactory response to at least a 3 month course of at least 1 DMARD at an adequate dose. - PsA: - >= 2 active peripheral joints (swollen or, in the absence of swelling, limited range of motion accompanied by either pain or tenderness) - A history of intolerance or an unsatisfactory response to at least a 3 month course of at least 1 DMARD at an adequate dose. - ERA: - >= 2 active peripheral joints (swollen or, in the absence of swelling, limited range of motion accompanied by either pain or tenderness) - A history of intolerance or an unsatisfactory response to at least 1 of the following: - at least a 1 month course of at least 1 NSAID at an adequate dose OR - at least a 3 month course of at least 1 DMARD at an adequate dose.
3. Subjects taking hydroxychloroquine, chloroquine, sulphasalazine, or MTX must have been receiving these for at least 3 months before the baseline visit. Only 1 of these DMARDs is to be taken throughout the study and the dose must be held stable for at least 8 weeks before the baseline visit.
4. All male and female subjects who, in the opinion of the investigator, are bologically capable of having children and are sexually active, must agree and commit to the use of a reliable method of birth control for the duration of the study and for 30 days after the last dose of investigational product.
- Female subjects who, in the opinion of the investigator, are biologically capable of having children must have a negative urine pregnancy test at screening and baseline (day 1) before administration of investigational product.
5. Either the subject or an available adult must be capable (according to the investigator’s judgment) of reconstituting and administering injections of SC etanercept.
6. The parent or legally authorized representative/guardian of the subject must be able to read and complete the protocol-specified efficacy assessments.
7. The subject and the parent or legally authorized representative/guardian of the subject must be willing and able to participate in all applicable aspects of the study
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E.4 | Principal exclusion criteria |
1. Subjects with systemic JIA, persistent oligoarticular JIA, polyarticular JIA, or undifferentiated arthritis per ILAR criteria. 2. Arthritis in an HLA-B27 positive male beginning after the 6th birthday (for PsA and extended oligoarticular JIA subtypes only as defined per ILAR criteria). 3. The presence of immunoglobulin M (IgM) rheumatoid factor (RF) on at least 2 occasions at least 3 months apart. 4. Subjects with active uveitis within 6 months of the baseline visit. 5. Subjects with other rheumatic diseases including but not limited to Lyme disease, systemic lupus erythematosus, systemic vasculitis, polymyositis, infectious or reactive arthritis, overlap syndrome (eg, Sharp’s syndrome), or Reiter’s syndrome. 6. Subjects with pustular, or erythrodermic psoriasis. 7. Prior treatment with any biologic drugs, including TNF inhibitors, abatacept, rituximab, and tocilizumab. 8. Receipt within 6 months before the baseline visit: - Immunosuppressive drugs (excluding corticosteroids) (eg, cyclophosphamide, cyclosporine, azathioprine). - Leflunomide. 9. Receipt within 3 months before the baseline visit: - Any investigational nonbiologic drugs or devices. 10. Receipt within 2 month before the baseline visit: - Any live (attenuated) vaccines 11. Receipt within 4 weeks before the baseline visit: - A combination of nonbiologic DMARDs (eg, hydroxychloroquine, chloroquine, sulphasalazine, MTX). - Nonbiologic DMARDs other than that which will be continued during the study (ie, hydroxychloroquine, chloroquine, sulphasalazine, or MTX), or those not listed under other exclusion criteria. - Ultraviolet A (UVA), ultraviolet B (UVB), or psoralen + UVA (PUVA) therapy for psoriatic lesions. 12. Receipt within 2 weeks before the baseline visit: - More than 1 NSAID, or a change in the dose or type of the NSAID, or an NSAID dose greater than the maximum recommended dose. - More than 0.2 mg/kg/day or > 10 mg/day, whichever is less, of oral prednisone or equivalent, or a change in the dose of prednisone or its equivalent. Receipt of intra-articular or soft tissue corticosteroid injection or bolus intramuscular (IM) or corticosteroids.
- Topical steroids, oral retinoids, topical vitamin A or D analog preparations or anthralin for psoriatic lesions (exception – topical therapies are permitted on the scalp, axillae, and groin at low to moderate strength; the dose and type must be held stable for at least 2 weeks before the baseline visit).
13. Any major illness/condition or evidence of unstable clinical condition (eg, cardiovascular [including congestive heart failure], cerebrovascular, neurologic, metabolic, immunologic, infectious, hepatic, renal condition, uncontrolled diabetes mellitus or hypertension), or any serious disorder (eg, current or history of alcohol or drug abuse, current or history of psychiatric disease) that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in and completion of the study, or could preclude the evaluation of the subject’s response, or interfere with the subject’s ability to give informed consent. 14. Pregnant or breastfeeding female subjects. 15. Cancer or history of cancer. 16. History of blood dyscrasias. 17. History of Macrophage Activating Syndrome (MAS). 18. History of demyelinating diseases (eg, multiple sclerosis or optic neuritis). 19. Documented immunodeficiency disease, including subjects with known human immunodeficiency virus (HIV) at the time of the screening visit. 20. Positive for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and/or hepatitis C virus (HCV). 21. History of clinically significant drug-induced liver injury, liver cirrhosis or fibrosis at any time before the baseline visit. 22. Active tuberculosis, history of tuberculosis or evidence of latent tuberculosis. A tuberculosis test, interpreted by the investigator according to local standards or country-specific guidelines, must be performed during the screening visit for subjects with no documentation of tuberculosis test results available within 12 weeks before the baseline visit. 23. Infection associated with hospitalization and/or parenteral antibiotics within 1 month before the baseline visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of Clinical Benefit in the Combined Population: Main endpoint: The main endpoint for the combined population is the proportion of subjects meeting the ACR Pedi 30 criteria at week 12, defined as > 30% improvement from baseline in at least 3 of 6 of the following variables: 1. PGA of Disease Activity on a 21-circle VAS (see attachment 5) 2. Parent/Patient Global Assessment on a 21-circle VAS (see attachment 6) 3. CHAQ 4. Number of active joints, defined as joints with swelling or, in the absence of swelling, joints with limitation of motion with pain and/or tenderness (see attachment 2) 5. Number of joints with limited range of motion (see attachment 2)
6. Laboratory measure of inflammation (CRP, see laboratory determination section) With worsening > 30% in no more than 1 of these variables.
Secondary Endpoints: The following additional assessments of clinical benefit will be assessed in the combined population: - ACR Pedi 30 at all time points other than week 12 - ACR Pedi 50, 70, 90, and 100 - Individual components of the ACR Pedi 30 - Pain Assessment on a 21-circle VAS. The Pain Assessment should be completed before the Joint Assessment and the Tender Entheseal Assessment. - Duration of morning stiffness - Disease status, where inactive disease is defined as no joints with active arthritis, a normal CRP, and a PGA of Disease Activity of 0 on a 21-circle VAS.
Evaluation of Clinical Benefit in the Subpopulations: Assessments of clinical benefit in the extended oligoarticular JIA, ERA, and PsA subpopulations will be assessed as follows:
For subjects with extended oligoarticular JIA: - ACR Pedi 30, 50, 70, 90, and 100 - Individual components of the ACR Pedi 30 - Pain Assessment on a 21-circle VAS - Duration of morning stiffness
For subjects with ERA: - ACR Pedi 30, 50, 70, 90, and 100 - Individual components of the ACR Pedi 30 - Pain Assessment on a 21-circle VAS - Duration of morning stiffness - Tender Entheseal Assessment (Mander 66). The Tender Entheseal Assessment should be completed after the Joint Assessment. - Overall Back Pain and Nocturnal Back Pain on a 100 mm VAS - Modified Schober’s test
For subjects with PsA: - ACR Pedi 30, 50, 70, 90, and 100 - Pain Assessment on a 21-circle VAS - Duation of morning stiffness - Psoriasis activity as reflected by BSA and PGA of Psoriasis
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity as measured by formation of anti-etanercept antibodies |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 78 |
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 | Information not present in EudraCT |
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 |
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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
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |