A Phase 1b/2 Multiple-Dose Safety and Pharmacokinetic/Pharmacodynamic Study of LY2189102 in Patients with Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-002660-29-HU
• Date of registration: 08/11/2005
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company Limited
• Public title: A Phase 1b/2 Multiple-Dose Safety and Pharmacokinetic/Pharmacodynamic Study of LY2189102 in Patients with Rheumatoid Arthritis
• Scientific title: A Phase 1b/2 Multiple-Dose Safety and Pharmacokinetic/Pharmacodynamic Study of LY2189102 in Patients with Rheumatoid Arthritis
• Date of first enrolment: 20/04/2007
• Target sample size: 135
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002660-29
• 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: yes Other trial design description: two-part modified dose escalation study If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Hungary, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Women and men who are 18 to 75 years of age.
[2] Women must not be at risk to become pregnant during study participation.
[3] Diagnosis of RA according to the American Rheumatism Association (ARA) 1988 Revised Criteria for the Classification of RA.
[4] Regular use of MTX (7.5 mg to 25 mg weekly) for at least 3 months (with stable doses for at least 2 months) at the time of study entry. Additional oral DMARDs are allowed, but not required.
[5] Active RA disease as defined by the following:
Part A:
- Presence of =3 swollen joints based on 28 diarthrodial joint assessment AND
- Presence of =3 tender joints based on 28 diarthrodial joint assessment
Part B:
- Presence of =6 swollen joints based on 66 diarthrodial joint assessment (=5 of which must be among those included in the 28 joint count), AND
- CRP measurement >2x upper limit of normal (ULN) (0.574 mg/dL), AND
- At least one of the following two criteria:
---- =6 tender joints based on 68 diarthrodial joint assessment (=5 of which must be among those included in the 28 joint count)
---- =45 minutes of early morning stiffness

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:
[12] History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, or metabolism or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data.
[16] Evidence of systemic conditions associated with inflammation other than RA.
[17] History of insulin-requiring diabetes mellitus.
[18] Frequent exacerbations of asthma or chronic obstructive pulmonary disease.
[19] History of respiratory infection within two weeks of study entry or a history of serious bacterial infections within two months of study entry.
[20] Prior exposure to these agents within the following timeframe:
- Anakinra (Kineret ® ) within 4 weeks of enrollment
- Etanercept (Enbrel ® ) within 4 weeks of enrollment
- Adalimumab (Humira ® ) within 8 weeks of enrollment
- Infliximab (Remicade ® ) within 8 weeks of enrollment
- Regeneron IL-1 Trap within 8 weeks of enrollment
- AMG108 (Anti-IL-1 receptor type 1 [IL-1R1] antibody) within 16 weeks of enrollment.
[21] In the judgment of the investigator, history of an inadequate therapeutic response to an adequate trial (at least one month) of a biologic agent targeting either IL-1 or TNF (Part B only).
[22] Prior use of therapies targeting B cells within the past one year (such as Lymphostat B, LY2127399, rituximab [Rituxan ™] or cyclophosphamide [Cytoxan ® ]) unless the investigator determines that the patient’s B cell counts have recovered.
[23] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication, or within 60 days of the time of study entry for any RA experimental agent.
[24] Use of any other biologic therapy for RA not specified by the protocol (for example, abatacept, anti-IL-6 receptor antibody, or anti-IL-15 antibody) within 5 half-lives of the last dose of the biologic agent (minimum 60 days).
[25] Prior serious systemic allergic reactions to biologic therapy.
[26] Use of other DMARDs other than MTX, hydroxychloroquine and sulfasalazine, in the 8 weeks prior to entry into this study (12 weeks for leflunomide).
[27] Received a live vaccination (for example, FluMist ®) within 3 months of study entry, or who are anticipated to receive live vaccines during the time period of participation in this study.
[28] Hemoglobin <10.0 g/dL.
[30] Liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) >1.2X ULN. The AST and ALT may be repeated once if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion.
[31] Evidence of hepatitis C and/or positive hepatitis C antibody.
[32] Evidence of hepatitis B and/or positive hepatitis B surface antigen.
[33] Evidence of human immunodeficiency virus (HIV) and/or positive test for antibodies to HIV.
[34] Evidence of tuberculosis (TB) as documented by positive tuberculin skin test (either history of past positive or screening tuberculin skin test >5 mm), medical history or chest radiograph. Study participants must have a screening purified protein derivative (PPD) test performed at screening and will be excluded if positive.
[35] Women who are pregnant or become pregnant during the study, or are breast-feeding.


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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Product Name: Anti IL-1ß antibody
Product Code: LY2189102
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: LY2189102
Other descriptive name: Anti IL-1ß antibody, subclass IgG4
Concentration unit: mg milligram(s)
Concentration type: not less then
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To examine the safety and tolerability of LY2189102 administered as multiple intravenous (IV) doses to Rheumatoid Arthritis (RA) patients who are receiving
stable doses of Methotrexate (MTX).

Primary end point(s): Safety and tolerability

Secondary Objective: To characterize LY2189102 pharmacokinetics during repeated IV dosing in RA patients who are taking concomitant MTX.

To characterize relationships between LY2189102 dose, exposure, and responses of selected pharmacodynamic endpoints, including:
- clinical measures of disease activity: Simple Disease Activity Index (SDAI) and/or Disease Activity Score (based on 28-joint count) (DAS28), AND
- biomarkers (for example, C-reactive protein [CRP] and other potential biomarkers of inflammation and/or structural damage), AND
- clinical measures of disability (Health Assessment Questionnaire [HAQ]).

Secondary ID(s)

H9C-MC-BBDE