A Phase 1b/2 Multiple-Dose Safety and Pharmacokinetic/Pharmacodynamic Study of LY2189102 in Patients with Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Registration Number
- EUCTR2005-002660-29-HU
- Lead Sponsor
- Eli Lilly and Company Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 135
[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
[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 <10.0 g/dL.
[30] Liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) >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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To examine the safety and tolerability of LY2189102 administered as multiple intravenous (IV) doses to Rheumatoid Arthritis (RA) patients who are receiving<br>stable doses of Methotrexate (MTX).;Secondary Objective: To characterize LY2189102 pharmacokinetics during repeated IV dosing in RA patients who are taking concomitant MTX.<br><br>To characterize relationships between LY2189102 dose, exposure, and responses of selected pharmacodynamic endpoints, including:<br>- clinical measures of disease activity: Simple Disease Activity Index (SDAI) and/or Disease Activity Score (based on 28-joint count) (DAS28), AND<br>- biomarkers (for example, C-reactive protein [CRP] and other potential biomarkers of inflammation and/or structural damage), AND<br>- clinical measures of disability (Health Assessment Questionnaire [HAQ]).;Primary end point(s): Safety and tolerability
- Secondary Outcome Measures
Name Time Method