Phase 2, Dose-Ranging Study of Multiple Subcutaneous Doses of LY2127399, an Anti-BAFF Human Antibody, in Patients with Active Rheumatoid Arthritis Despite Ongoing Methotrexate Therapy

Phase 1

Conditions: Rheumatoid arthritis
MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

Registration Number: EUCTR2008-004894-16-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: 150

Inclusion Criteria

[1] Ambulatory males or females between the ages of 18 and 75 years, inclusive.
[2] Women must not be pregnant or breastfeeding during study participation. Women of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopause) must have a negative pregnancy test and must use an acceptable form of contraception during the study. Methods of contraception considered acceptable are oral contraceptives, contraceptive patch, intrauterine device (IUD), vaginal ring, diaphragm, or condom with contraceptive gel.
[3] Diagnosis of RA according to the ARA 1987 Revised Criteria for the Classification of RA (Arnett et al. 1988).
[4] Regular use of MTX for at least 16 weeks, and at a stable dose between 10 and 25 mg/wk, inclusive, for at least 8 weeks prior to baseline. Local standard of care should be followed for concomitant administration of folic acid.
[5] History of, or current, positive rheumatoid factor (RF) test.
[6] ACR functional class I, II, or III (Protocol Attachment BCDH.2).
[7] Have active RA defined as at least 5 swollen and at least 5 tender joints based on the 28 joint count specified (Section 6.1.2.2 [Tender Joint Counts] and Section 6.1.2.3 [Swollen Joint Counts]).
[8] Have a screening CRP of at least 1.2 times upper limit of normal (ULN).
[9] Clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations as judged by the investigator.
[10] Venous access sufficient to allow blood sampling as per the protocol.
[11] Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
[12] Are able to read, understand, and give written informed consent approved by Lilly or its designee and the ethical review board (ERB) governing the site.
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

[1] Have received any parenteral corticosteroid administered by intraarticular, intramuscular, or IV injection within 4 weeks of baseline.
[2] Within 4 weeks prior to baseline, either 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.
[3] Have received any B cell biotherapies at anytime in the past, whether the indication for therapy was RA or not.
[4] Have been treated for at least 3 months at approved doses with at least 1 biologic TNFa inhibitor therapy and have had an inadequate efficacy response to such treatment in the opinion of the investigator. Patients must have stopped etanercept =28 days, and infliximab, adalimumab, or other biologic TNFa inhibitor therapy =56 days prior to baseline.
[5] Have had an inadequate response to treatment with 3 or more of the following DMARDs prescribed alone or in combination at approved doses for a minimum of 3 months: abatacept, leflunomide, azathioprine, cyclosporine, and sulfasalazine.
[6] Use of other DMARDs other than MTX, hydroxychloroquine, or sulfasalazine, in the 8 weeks prior to baseline. If on hydroxychloroquine or sulfasalazine, must be on the drug for 16 weeks and at a stable dose for at least 8 weeks prior to baseline.
[7] Use of leflunomide in the 12 weeks prior to baseline. Cholestyramine may be used to shorten the washout period for leflunomide, according to standard protocol
[8] Use of NSAIDs for <2 weeks prior to baseline.
[9] Diagnosis of any systemic inflammatory condition other than RA.
[10] Evidence of active vasculitis.
[11] Diagnosis of Felty’s syndrome.
[12] Surgical treatment of a joint that is to be assessed in the study within 2 months of study enrollment, or will require such during the study.
[13] Have previously completed or withdrawn from this study or any other study investigating LY2127399.
[14] Abnormality in the 12-lead ECG that in the opinion of the investigator increases the risk of participating in the study or a Bazett’s corrected QT interval >450 msec for men and >470 msec for women.
[15] Uncontrolled arterial hypertension characterized (sBP >160 mmHg or dBP >100 mmHg.
[16] 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.
[17] History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders constituting a risk when taking the study medication or of interfering with the interpretation of data. Subjects on a stable dose of thyroid replacement therapy during the 6 months preceding baseline who are clinically or biochemically euthyroid may enroll in the trial.
[18] Evidence of significant active neuropsychiatric disease, in the opinion of the investigator.
[19] Serious bacterial infection within 6 months of enrollment.
[20] Symptomatic herpes zoster within 3 months of enrollment.
[21] Evidence of HIV and/or positive human HIV antibodies.
[22] Evidence of hepatitis C and/or positive hepatitis C antibody.
[23] Evidence of hepatitis B and/or positive hepatitis B surface antigen.
[24] Evidence or suspicion of active TB by medical history, physical examination and/or screening chest radiograph.
[25] At the time of screening, a positive purified protein derivative (PPD) test for TB. For the purpose of this study, a positive test is defined as induration

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

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