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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-004894-16-PL
• Date of registration: 18/12/2008
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company limited
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 15/01/2009
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004894-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic, Germany, Hungary, Poland

Key inclusion & exclusion criteria

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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: LY2127399
Pharmaceutical Form: Powder for solution for injection
Current Sponsor code: LY2127399
Other descriptive name: Anti LP40 antibody, subclass IgG4 LA294
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 48-
Pharmaceutical form of the placebo: Injection*
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): ACR50 responder index (based on the 28 joint count) at 24 weeks after baseline.

Secondary Objective: • estimate maximum response to LY2127399, ED95, and smallest dose achieving maximum response of ACR20 and ACR50 at 24 weeks
• determine whether there is a minimally effective dose (smallest dose with at least 25% absolute efficacy difference from placebo in ACR50 and ACR20) and to estimate that dose
• evaluate LY2127399 dose-ACR50 response and dose-ACR20 response relationships at 24 weeks relative to placebo
• characterize relationships between LY2127399 dose, exposure, and response of selected PD endpoints
• evaluate LY2127399 safety and tolerability compared to placebo
• evaluate PD of selected peripheral B cell subsets compared to placebo
• explore potential associations between selected biomarkers and selected disease activity measures
• further characterize LY2127399 PK in RA patients on MTX therapy
• evaluate potential effect of LY2127399 compared to placebo on additional patient-reported outcomes as measured by the:
? FACIT Fatigue Scale
? Medical Outcomes SF-36

Main Objective: To test the hypothesis that the ACR50 response after 24 weeks for the smallest dose that achieves at least 95% of the maximal efficacy (ED95) of LY2127399 is significantly greater than for placebo, when study drug is administered subcutaneously once monthly in patients with active RA despite ongoing MTX therapy.

Secondary ID(s)

2008-004894-16-DE

H9B-MC-BCDH