Rheumatoid Arthritis
Conditions
Interventions
Product Name: Anti IL-1ß antibody
Product Code: LY2189102
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: LY2189102
Other descriptive name: Anti IL-1ß antibody, subclass Ig
Sponsors
Eli Lilly and Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Women and men who are 18 to 75 years of age. [2] Women must not be at risk to become pregnant during study participation. [3] Diagnosis of RA according to the American Rheumatism Association (ARA) 1988 Revised Criteria for the Classification of RA. [4] Regular use of MTX (7.5 mg to 25 mg weekly) for at least 3 months (with stable doses for at least 2 months) at the time of study entry. Additional oral DMARDs are allowed, but not required. [5] Active RA disease as defined by the following: Part A: - Presence of =3 swollen joints based on 28 diarthrodial joint assessment AND - Presence of =3 tender joints based on 28 diarthrodial joint assessment Part B: - Presence of =6 swollen joints based on 66 diarthrodial joint assessment (=5 of which must be among those included in the 28 joint count), AND - CRP measurement >2x upper limit of normal (ULN) (0.574 mg/dL), AND - At least one of the following two criteria: ---- =6 tender joints based on 68 diarthrodial joint assessment (=5 of which must be among those included in the 28 joint count) ---- =45 minutes of early morning stiffness Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: [12] History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, or metabolism or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data. [16] Evidence of systemic conditions associated with inflammation other than RA. [17] History of insulin-requiring diabetes mellitus. [18] Frequent exacerbations of asthma or chronic obstructive pulmonary disease. [19] History of respiratory infection within two weeks of study entry or a history of serious bacterial infections within two months of study entry. [20] Prior exposure to these agents within the following timeframe: - Anakinra (Kineret ® ) within 4 weeks of enrollment - Etanercept (Enbrel ® ) within 4 weeks of enrollment - Adalimumab (Humira ® ) within 8 weeks of enrollment - Infliximab (Remicade ® ) within 8 weeks of enrollment - Regeneron IL-1 Trap within 8 weeks of enrollment - AMG108 (Anti-IL-1 receptor type 1 [IL-1R1] antibody) within 16 weeks of enrollment. [21] In the judgment of the investigator, history of an inadequate therapeutic response to an adequate trial (at least one month) of a biologic agent targeting either IL-1 or TNF (Part B only). [22] Prior use of therapies targeting B cells within the past one year (such as Lymphostat B, LY2127399, rituximab [Rituxan ™] or cyclophosphamide [Cytoxan ® ]) unless the investigator determines that the patient’s B cell counts have recovered. [23] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication, or within 60 days of the time of study entry for any RA experimental agent. [24] Use of any other biologic therapy for RA not specified by the protocol (for example, abatacept, anti-IL-6 receptor antibody, or anti-IL-15 antibody) within 5 half-lives of the last dose of the biologic agent (minimum 60 days). [25] Prior serious systemic allergic reactions to biologic therapy. [26] Use of other DMARDs other than MTX, hydroxychloroquine and sulfasalazine, in the 8 weeks prior to entry into this study (12 weeks for leflunomide). [27] Received a live vaccination (for example, FluMist ®) within 3 months of study entry, or who are anticipated to receive live vaccines during the time period of participation in this study. [28] Hemoglobin 1.2X ULN. The AST and ALT may be repeated once if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion. [31] Evidence of hepatitis C and/or positive hepatitis C antibody. [32] Evidence of hepatitis B and/or positive hepatitis B surface antigen. [33] Evidence of human immunodeficiency virus (HIV) and/or positive test for antibodies to HIV. [34] Evidence of tuberculosis (TB) as documented by positive tuberculin skin test (either history of past positive or screening tuberculin skin test >5 mm), medical history or chest radiograph. Study participants must have a screening purified protein derivative (PPD) test performed at screening and will be excluded if positive. [35] Women who are pregnant or become pregnant during the study, or are breast-feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the safety and tolerability of LY2189102 administered as multiple intravenous (IV) doses to Rheumatoid Arthritis (RA) patients who are receiving stable doses of Methotrexate (MTX).;Secondary Objective: To characterize LY2189102 pharmacokinetics during repeated IV dosing in RA patients who are taking concomitant MTX. To characterize relationships between LY2189102 dose, exposure, and responses of selected pharmacodynamic endpoints, including: - clinical measures of disease activity: Simple Disease Activity Index (SDAI) and/or Disease Activity Score (based on 28-joint count) (DAS28), AND - biomarkers (for example, C-reactive protein [CRP] and other potential biomarkers of inflammation and/or structural damage), AND - clinical measures of disability (Health Assessment Questionnaire [HAQ]).;Primary end point(s): Safety and tolerability | — |
Countries
Hungary, Spain
Outcome results
None listed