A Phase 2 Study of Multiple Intravenous Doses of LY2127399, an Anti-BAFF Human Antibody, in Patients with Rheumatoid Arthritis on Concomitant Methotrexate and an Inadequate Response to TNFa Inhibitor Therapy - BCDG

• Register: EUCTR
• Last refreshed on: 26 November 2013
• Main ID: EUCTR2008-001105-42-BE
• Date of registration: 14/07/2008
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Phase 2 Study of Multiple Intravenous Doses of LY2127399, an Anti-BAFF Human Antibody, in Patients with Rheumatoid Arthritis on Concomitant Methotrexate and an Inadequate Response to TNFa Inhibitor Therapy - BCDG
• Scientific title: A Phase 2 Study of Multiple Intravenous Doses of LY2127399, an Anti-BAFF Human Antibody, in Patients with Rheumatoid Arthritis on Concomitant Methotrexate and an Inadequate Response to TNFa Inhibitor Therapy - BCDG
• Date of first enrolment: 16/09/2008
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001105-42
• 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

Austria, Belgium, France, Germany, Poland

Key inclusion & exclusion criteria

Inclusion criteria:
•Ambulatory males or females between the ages of 18 and 75 years, inclusive.
•Women must not be pregnant, breastfeeding, or at risk to become pregnant during study participation and must have a negative pregnancy test. Women of childbearing potential must use a medically permitted form of contraception during the whole study and until B cell counts have returned to baseline levels or to within normal range (as specified by the performing laboratory). Methods of contraception considered acceptable are oral contraceptives, contraceptive patch, intrauterine device (IUD), vaginal ring, diaphragm, or condom with contraceptive gel.
•Diagnosis of RA according to the ARA 1987 Revised Criteria for the Classification of RA (Arnett et al. 1988).
•Have been treated for at least 3 months at approved doses with at least biologic TNFa inhibitor therapy and have had an inadequate response to such treatment in the opinion of the investigator OR have been intolerant to these agents regardless of treatment duration. Patients must have stopped etanercept >28 days, and infliximab or adalimumab >56 days prior to baseline.
•Regular use of methotrexate for 16 weeks, and at a stable dose between 10 and 25 mg/wk, inclusive, for at least 8 weeks prior to baseline.
•History of, or current, seropositive rheumatoid factor (RF).
•ACR functional class I, II, or III.
•Have active RA defined as at least 5/28 swollen and at least 5/28 tender joints based on the joint count specified.
•Have a screening CRP of at least 1.2X ULN or a screening ESR of at least 28 mm/hr.
•Clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations as judged by the investigator.
•Venous access sufficient to allow study drug administration and blood sampling as per the protocol.
•Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
•Have given 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:
• Had symptomatic herpes zoster within 3 months of enrollment.
• Evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies.
• Evidence of hepatitis C and/or positive hepatitis C antibody.
• Evidence of hepatitis B and/or positive hepatitis B surface antigen.
• Evidence or suspicion of active tuberculosis (TB) by medical history, physical examination, and/or screening chest radiograph.
• At the time of screening, a positive PPD test for TB. For the purpose of this study, a positive test is defined as induration =10 mm, between approximately 2 and 3 days after test application. Exceptions to this criterion include patients with a history of a positive PPD who have been treated with isoniazid (INH) (documented) for at least 6 months, or patients with a previous diagnosis of TB who have received appropriate treatment (documented) and have not been re-exposed to TB since their treatment was completed.
• Have had other recent or ongoing infection that in the opinion of the investigator poses an unacceptable risk to participate in the study.
• Exposed to a live vaccine within 3 months of enrollment or expected to need/receive a live vaccine during the course of the study.
• Have significant hematological abnormalities, including haemoglobin less than 8.0 g/dL, total platelet count less than 100,000/µL, total white blood cell (WBC) count less than 3000/µL, neutrophil count less than 1000/µL, or lymphocyte count less than 200 cells/µL.
• Have a screening serum creatinine >2.0 mg/dL.
• Have known hypogammaglobulinemia or a serum IgG, IgM, or IgA concentration less than the lower limit of normal.
• Have any history of chronic liver disease or with serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration >1.2x the upper limit of normal. The AST and ALT may be repeated once within a week if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion.
• Blood donation of more than 500 mL within the last month.
• Women with a positive pregnancy test or women who are lactating.



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 Code: LY2127399
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: LY2127399
Other descriptive name: Anti LP40 antibody, subclass IgG4 LA294
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: • To evaluate LY2127399 efficacy compared to placebo over the 24-week study period as assessed by the:
- Individual components of the ACR Core Set
- Disease Activity Score based on the 28 joint count
- EULAR28
• To evaluate LY2127399 safety and tolerability compared to placebo
• To evaluate PD of disease-related biomarkers as compared to placebo.
• To explore the potential associations between selected biomarkers and selected disease activity measures
• To characterize LY2127399 PK in RA patients with inadequate response or intolerance to TNFa inhibitor therapy.
• To evaluate the impact of LY2127399 compared to placebo over the 24-week study period on patient-reported outcomes as measured by the:
- FACIT Fatigue Scale
- Medical Outcomes Study 36-Item Short Form Health Survey

Main Objective: To evaluate LY2127399 efficacy assessed by the proportion of patients who achieve an ACR50 response compared to placebo at 24 weeks in patients with RA, who have had an inadequate response or intolerance to treatment with at least 1 biologic TNFa inhibitor therapy.

Primary end point(s): The primary efficacy variable is ACR50 responder index at 24 weeks after baseline.

Secondary ID(s)

H9B-MC-BCDG