Extended oligoarticular juvenile idiopathic arthritis (JIA) Enthesitis-related arthritis (ERA) Psoriatic arthritis (PsA) MedDRA version: 9.1 Level: LLT Classification code 10003246 Term: Arthritis
Conditions
Interventions
Trade Name: Enbrel
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Etanercept
CAS Number: 185243-69-0
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc., Clinical Research and Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects must have met ILAR criteria for diagnosis of 1 of the following JIA subtypes 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 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 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 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, sulphasalazine, or methotrexate must have been receiving these for at least 3 months before the baseline visit. Only 1 DMARD 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 biologically capable of having children, 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. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with systemic JIA, persistent oligoarticular JIA, polyarticular JIA, or undifferentiated arthritis per ILAR criteria. 2. Subjects positive for HLA-B27 (PsA and extended oligoarticular JIA subtypes only) or rheumatoid factor (RF) at the screening visit. 3. Subjects with active uveitis within 6 months of the baseline visit. 4. 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. 5. Subjects with guttate, pustular, or erythrodermic psoriasis. 6. Prior treatment with any biologic drugs, including TNF inhibitors, abatacept, rituximab,and tocilizumab. 7. Receipt within 6 months before the baseline visit: - Immunosuppressive drugs (excluding corticosteroids) (eg, cyclophosphamide). - Leflunomide. 8. Receipt within 3 months before the baseline visit: - Nonbiologic DMARDs other than hydroxychloroquine, sulphasalazine, MTX, or those not listed under other exclusion criteria. - Any investigational nonbiologic drugs or devices. - Any live (attenuated) vaccines. 9. Receipt within 4 weeks before the baseline visit: - Ultraviolet A (UVA), ultraviolet B (UVB), or psoralen + UVA (PUVA) therapy for psoriatic lesions 10. 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 intraarticular or soft tissue corticosteroid injection or bolus intramuscular (IM) or intravenous (IV) treatment with 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). 11. 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. 12. Pregnant or breastfeeding female subjects 13. Cancer or history of cancer. 14. History of blood dyscrasias. 15. History of Macrophage Activating Syndrome (MAS). 16. History of demyelinating diseases (eg, multiple sclerosis or optic neuritis). 17. Documented immunodeficiency disease, including subjects with known human immunodeficiency virus (HIV) at the time of the screening visit. 18. Positive for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) and/or hepatitis C virus (HCV). 19. History of drug-induced liver injury, liver cirrhosis or fibrosis at any time before the baseline visit. 20. Any of the following laboratory abnormalities at screening: - Hemoglobin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: 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. ;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 2. Parent/Patient Global Assessment on a 21-circle VAS 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 (75 joints) 5. Number of joints with limited range of motion (69 joints) 6. Laboratory measure of inflammation (CRP) 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 - 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 oligoa | — |
Countries
Belgium, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Netherlands, Slovenia, Spain, Sweden
Outcome results
None listed