A study to evaluate the efficacy of different doses of LY3009104 therapy compared to placebo in patients with Rheumatoid Arthritis who are on ongoing methotrexate background therapy.
- Conditions
- Rheumatoid ArthritisMedDRA version: 14.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2010-022504-42-HU
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 270
Parts A & B
[1] Ambulatory males or females between the ages of 18 and 75 years, inclusive, at time of study entry.
[1a] Male patients:
Agree to use two forms of highly effective methods of birth control with female partners of childbearing potential during the study.
[1b] Female patients:
Females must not be pregnant, breastfeeding, or at risk to become pregnant during study participation.
Female patients of childbearing potential, must have a negative serum
pregnancy test at the time of enrollment and agree to use two forms of
highly effective methods of birth control or remain abstinent for at least 28 days following the last dose of study drug. OR Must be female patients of non-childbearing potential, defined as:
• women who have had surgical sterilization (hysterectomy or bilateral
oophorectomy or tubal ligation),
• women =60 years of age,
• women =40 and <60 years of age who have had a cessation of menses for at least 12 months and a follicle-stimulating hormone (FSH) test confirming non-childbearing potential (FSH =40 mIU/mL), or
• women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (also
referred to as Congenital Absence of Uterus and Vagina [CAUV]).
[2] Diagnosis of adult-onset RA (of at least 6 months duration but not longer than 15 years prior to screening) according to the ARA 1987 Revised Criteria for the Classification of RA.
[3] Have active RA defined as at least 8 swollen and at least 8 tender joints based on the 66/68 joint count.
[4] Regular use of MTX for at least 12 weeks, and treatment at a stable dose of 10 to 25 mg/week for at least 8 weeks prior to baseline. The dose of MTX should remain stable throughout the study, but may be adjusted for safety reasons. Local standard of care should be followed for concomitant administration of folic acid.
[5] For patients receiving corticosteroids, they must be on a dose not to exceed 10 mg of prednisone daily (or equivalent) and have been on a the same dosing regimen for at least 6 weeks prior to randomization.
[6] ACR functional class I, II, or III.
[7] Have C-reactive protein (CRP) measurement > 1.2 times upper limit of normal (ULN) or Erythrocyte Sedimentation Rate (ESR) > upper limit of normal (28 mm/hr). The CRP and ESR may be repeated once during the screening period at the discretion of the investigator, and the repeat results may be accepted for study eligibility purposes.
[8] Have laboratory values that in the opinion of the investigator do not pose an unacceptable risk to the patient if study drug would be administered.
[9] Venous access sufficient to allow blood sampling as per the protocol.
[10] Are reliable and willing to be available for the duration of the study and are willing to follow study procedures.
[11] Are able to read, understand, and give written informed consent approved by Lilly (or designee) and the ethical review board (ERB) governing the site, and are able to read and understand all questionnaires given at study visits.
Study Part C
[12] Continue to meet inclusion criteria [1a] or [1b] and [8] to [10] of Parts A and B.
[13] Have completed the 24 weeks (Visit 1 to Visit 10) of participation in Parts A and B of the study without permanent study drug discontinuation. Patients who complete Part A and Part B before amendment (a) is active will be eligible to enter Part C of the study only if Part C becomes active prior to the patient’s Follow-Up Visit (28 days after the last dose of study drug).
[14] Give written informed consent approved by Li
Parts A & B
[15] Received any parenteral corticosteroid administered by intra-articular, intramuscular, or IV injection within 6 weeks prior to baseline.
[17] Used NSAIDs for less than 4 weeks prior to baseline. If on NSAIDs , must be on a stable dose for at least 4 weeks prior to baseline and must remain on a stable dose throughout Part A and Part B of the study.
[18] Received any prior biologic DMARD therapy (such as TNFa, IL-1, IL-6, T-cell or B-cell targeted therapies).
[20] Received prior treatment with an oral JAK inhibitor.
[21] Used DMARDs (for example, gold salts, cyclosporine, azathioprine, or any other immunosuppressives) other than stable treatment of MTX, hydroxychloroquine (up to 400 mg/day), and/or sulfasalazine (up to 3000 mg/day) in the 8 weeks prior to baseline.
[22] Use of leflunomide in the 12 weeks prior to baseline (or a minimum of 4 weeks prior to baseline will be required if the standard 11 days of chlolestyramine is used to washout leflunomide).
[23] Have active fibromyalgia that would make it difficult to appropriately assess RA activity for the purposes of this study or have a diagnosis of any systemic inflammatory condition other than RA. Patients with secondary Sjogren's syndrome with RA are not excluded.
[24] Evidence of active vasculitis.
[25] Diagnosis of Felty’s syndrome.
[26] Had surgical treatment of a joint that is to be assessed in the study within 2 months of study baseline or will require such during the study.
[27] An abnormality in the 12-lead ECG that in the opinion of the investigator increases the risk of participating in the study.
[28] Uncontrolled arterial hypertension characterized by repeated systolic BP >160 mmHg or repeated diastolic BP >100 mmHg, measured twice during the screening visit.
[30] History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders that in the opinion of the investigator could constitute a risk when taking the study drug or of interfere with the interpretation of data. Patients on a stable dose of thyroid replacement therapy during the 6 months preceding baseline who are clinically or biochemically euthyroid may enroll.
[32] Current or recent (<30 days prior to screening) viral, bacterial, fungal, or parasitic infection.
[33] Had a serious infection or atypical mycobacterial infection within 6 months prior to screening.
[34] Symptomatic herpes zoster or herpes simplex infection within 90 days prior to baseline.
[35] History of disseminated/complicated herpes zoster (for example,
multidermatomal involvement, ophthalmic zoster, CNS involvement).
[36] Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies.
[37] Hepatitis C virus (HCV; positive for anti-hepatitis C antibody with confirmed presence of HCV).
[38] Evidence of active hepatitis B (positive for hepatitis B surface antigen [HBsAg+]) OR are positive for hepatitis B core antibody and negative for hepatitis B surface antibody.
[39] Evidence of active tuberculosis (TB) or evidence of latent TB
[41] Have any significant hematological abnormalities listed below:
o Hemoglobin less than 10.0 g/dL,
o Total platelet count less than 100,000/µL ,
o Total white blood cell (WBC) count less than 2500/µL,
o Neutrophil count equal to or less than 1200/µL
o Lymphocyte count equal to or less than 750 cells/µL.
[42] Have estimated glomerular filtration rate (GFR) from serum creatinine using the Modification of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method