Rheumatoid Arthritis MedDRA version: 14.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: LY2439821
Product Code: LY2439821
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: N.A.
Current Sponsor code: LY2439821
Concentration unit: mg milligram(s)
Con
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Common to Both Populations [1] Ambulatory males or females, 18 years to 75 years, inclusive. [1a] Male patients: Agree to use a reliable method of birth control during the study. [1b] Female patients: Are women of childbearing potential who test negative for pregnancy and agree to use a reliable method of birth control during the study. Methods of contraception considered acceptable are oral contraceptives, contraceptive patch, intrauterine device, vaginal ring, diaphragm, or condom with contraceptive gel. OR Are women who have undergone surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation). OR Are post menopausal female patients defined as women >45 years of age who have had a cessation of menses for at least 12 months OR are women between 40 and 45 years of age who test negative for pregnancy, have had a cessation of menses for at least 12 months, and have a Follicle Stimulating Hormone (FSH) value >40 mIU/mL. [2] RA diagnosis by American Rheumatism Association 1987 Revised Criteria. [4] At least 6 tender and at least 6 swollen joints. [5] C-reactive protein (CRP) >ULN or erythrocyte sedimentation rate (ESR) of at least 28 mm/hr. Inclusion Criterion Specific to the bDMARD-naive Population [6] Regular use of MTX for at least 12 weeks, and stable treatment (7.5 mg/week to 25 mg/week) for at least 8 weeks prior to baseline. Inclusion Criterion Specific to the TNFa-IR Population [7] TNFa-IR patients must have been treated at approved doses with at least 1 biologic TNFa inhibitor therapy and in the opinion of the investigator EITHER: a) had an insufficient response to at least 3 months of treatment (stopped due to insufficient efficacy), OR b) have been intolerant of such treatment, regardless of treatment duration. [8] Regular use of at least 1 conventional DMARD in a stable treatment regimen as specified. Some of the included criteria have been condensed from protocol language. Refer to protocol pages 39-40 for the full list and full text of all Inclusion/Exclusion Criteria. 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 380 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: Exclusion Criteria Specific to the bDMARD naive Population [9] Have received any prior biologic DMARD therapy. [10] Have had, in the opinion of the investigator, an inadequate response to treatment with 5 or more conventional DMARDs (such as leflunomide, azathioprine, cyclosporine, hydroxychloroquine, gold salts, and sulfasalazine), prescribed alone or in combination, at approved doses, for a minimum of 3 months. [11] Use of DMARDs other than MTX, hydroxychloroquine, or sulfasalazine (for example, gold salts, cyclosporine, azathioprine, or any other immunosuppressives) in the 8 weeks prior to baseline. [12] Use of leflunomide in the 12 weeks prior to baseline. Cholestyramine may be used to shorten the washout period from 12 to 4 weeks for leflunomide, if used according to standard protocol (Van Riel et al. 2004). Exclusion Criteria Specific to the TNFa-IR Population [13] Concurrent or recent use of any biologic DMARDs or biologic TNFa inhibitor therapies within specified washout periods. Exclusion Criteria Common to Both Populations [15] Concomitant use of NSAIDs in Part A, unless patient is on stable dose for at least 2 weeks prior to baseline. [16] Parenteral glucocorticoid administered by intra-articular, intramuscular, or IV injection within 4 weeks of baseline, or for whom a parenteral injection of glucocorticosteroids is anticipated during the course of the study. [17] Use of oral corticosteroids (at average daily doses of >10 mg/day of prednisone or its equivalent) or use of variable doses of oral corticosteroids within 4 weeks prior to baseline. [18] Live vaccination within 12 weeks before baseline, or intend to have a live vaccination during the course of the study, or have participated in a vaccine clinical study within 12 weeks prior to baseline. [19] Have a diagnosis of any systemic inflammatory condition other than RA, such as juvenile RA, seronegative spondyloarthropathy, Crohn’s disease, ulcerative colitis, psoriasis, or psoriatic arthritis. [23] Have had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease. [24] Have findings, or a history of, clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders, which in the opinion of the investigator, place the patient at an unacceptable risk for participation in the study or of interfering with the interpretation of data. [26] Serious bacterial infection within 3 months of entry, or a recent or ongoing infection that in the opinion of the investigator poses an unacceptable risk to participate in the study. [27] Evidence or suspicion of active tuberculosis (TB) by medical history, physical examination, and/or chest radiograph or documentation of TB by a positive purified protein derivative (PPD) test. Exceptions to this criterion include patients with latent TB, who have a documented treatment history with isoniazid (INH) for at least 6 months or a rifampicin-based regimen for at least 3 months; or patients who have received documented, completed, effective chemotherapy for active TB with no history of re-exposure since their treatment was completed; or patients with a history of BCG vaccination within the 10 years prior to baseline and who have a negative chest x-ray. [28] Uncontr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: bDMARD naive population ONLY To determine the dose-response relationship of LY2439821 at week 12, as measured by the proportion of American College of Rheumatology 20 (ACR20) responders. ;Secondary Objective: TNFa-IR population ONLY • To evaluate the efficacy of LY2439821 at Week 12 compared to placebo as measured by the proportion of ACR20 responders. bDMARD-naive population ONLY • To estimate the smallest doses that achieve 10%, 50%, and 90% of the maximum ACR20 response (ED10, 50, and 90, respectively) at Week 12. • To evaluate the dose-response relationship of LY2439821 at Week 12 and the doses that achieve 10%, 50%, and 90% of the maximum response (ED10, 50, and 90, respectively) at Week 12 as measured by the Disease Activity Score [DAS] based on the 28 diarthroidal joint count (DAS28) and the ACR50 response rates. BOTH bDMARD-naive AND TNFa-IR populations, separately • see.....Protocol page 32-33;Primary end point(s): To determine the dose-response relationship of LY2439821 at week 12, as measured by the proportion of ACR20 responders. Biologic disease modifiying anti-rheumatic drug-naive population (bDMARD-naive) only;Timepoint(s) of evaluation of this end point: week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of American College of Rheumatology (ACR) 20 responders; Tumor Necrosis Factor alpha-inadequate responder population (TNF-a-IR) only Smallest doses that achieve 10%, 50%, and 90% of the maximum American College of Rheumatology (ACR) 20 response; Biologic disease modifying anti-rheumatic drug-naive population (bDMARD-naive) only Smallest doses that achieve 10%; 50% and 90% of maximum Disease Activity Score (DAS) 28 response; Biologic disease modifying anti-rheumatic drug-naive population (bDMARD-naive) only Smallest doses that achieve 10%; 50% and 90% of maximum American College of Rheumatology (ACR) 50 response; biologic modifying anti-rheumatic drug naive population (bDMARD-naive) only Change from baseline in Desease Activity Score (DAS28) Proportion of American College of Rheumatology (ACR)20/50/70 responders Change from baseline in individual components of the American College of Rheumatology (ACR) core set Proportion of patients in European League Against RheumatismRheumatism Responder Index (EULAR28) Actual value of American College of Rheumatology (ACR)-N Change from baseline in duration of morning stiffness (minutes) Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relationship between exposure and response of individual components of the American College of Rheumatology (ACR) core set Relationship between exposure and response of American College of Rheumatology (ACR) 20/50/70N Relationship between exposure and response of Disease Actitivy Score (DAS)28 Relationship between exposure and response of European League Against Rhematism (EULAR)28;Timepoint(s) of evaluation of this end point: First 4 bullets at Week 12 Rest of secondary endopoints at Week 72 | — |
Countries
Argentina, Chile, Germany, India, Korea, Republic of, Peru, Poland, Romania, Russian Federation, Taiwan
Contacts
Public ContactClinical Trial Information
Eli Lilly
Outcome results
None listed