A Study in Patients With Rheumatoid Arthritis - Full Text View

Sponsor:	Eli Lilly and Company
Information provided by (Responsible Party):	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00966875

Purpose

The primary purpose of the study is to help answer the following research questions, and not to provide treatment for Rheumatoid Arthritis (RA):

The safety of LY2439821 and any side effects that might be associated with it.
Whether LY2439821 can help patients with active RA.
How much LY2439821 should be given to patients.

Condition	Intervention	Phase
Rheumatoid Arthritis	Biological: LY2439821 Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 2 Dose-Ranging Study of Multiple Subcutaneous Doses of LY2439821 (an Anti-IL-17 Antibody) in Patients With Active Rheumatoid Arthritis on Concomitant DMARD Therapy

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Dose-response relationship measured by the proportion of American College of Rheumatology (ACR) 20 responders; Biologic disease modifying anti-rheumatic drug-naive population (bDMARD-naive) only [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of American College of Rheumatology (ACR) 20 responders; Tumor Necrosis Factor alpha - inadequate responder population (TNFa-IR) only [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Smallest doses that achieve 10%, 50%, and 90% of the maximum American College of Rheumatology (ACR) 20 response; Biologic disease modifying anti-rheumatic drug-naive population (bDMARD-naive) only [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Smallest doses that achieve 10%, 50%, and 90% of the maximum Disease Activity Score (DAS) 28 response; Biologic disease modifying anti-rheumatic drug-naive population (bDMARD-naive) only [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Smallest doses that achieve 10%, 50%, and 90% of the maximum American College of Rheumatology (ACR) 50 response; Biologic disease modifying anti-rheumatic drug-naive population (bDMARD-naive) only [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Change from baseline in Disease Activity Score (DAS28) [ Time Frame: Baseline, through Week 72 ] [ Designated as safety issue: No ]
Proportion of American College of Rheumatology (ACR) 20/50/70 responders [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
Change from baseline in individual components of the American College of Rheumatology (ACR) core set [ Time Frame: Baseline, through Week 72 ] [ Designated as safety issue: No ]
Proportion of patients in European League Against Rheumatism Responder Index (EULAR28) [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
Actual value of American College of Rheumatology (ACR)-N [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
Change from baseline in duration of morning stiffness (minutes) [ Time Frame: Baseline, through Week 72 ] [ Designated as safety issue: No ]
Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, through Week 72 ] [ Designated as safety issue: No ]
Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale [ Time Frame: Baseline, through Week 72 ] [ Designated as safety issue: No ]
Relationship between exposure and response of individual components of the American College of Rheumatology (ACR) core set [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
Relationship between exposure and response of American College of Rheumatology (ACR) 20/50/70/N [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
Relationship between exposure and response of Disease Activity Score (DAS) 28 [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
Relationship between exposure and response of European League Against Rheumatism (EULAR) 28 [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
Pharmacokinetics Cmax [ Time Frame: Through Week 72 ] [ Designated as safety issue: No ]
anti-LY2439821 antibodies [ Time Frame: Through Week 72 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	429
Study Start Date:	August 2009
Estimated Study Completion Date:	July 2012
Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 3mg LY2439821 [bDMARD-naive population] 3 mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Biological: LY2439821 subcutaneous Other Name: LY2439821
Experimental: 10mg LY2439821 [bDMARD-naive population] 10mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Biological: LY2439821 subcutaneous Other Name: LY2439821
Experimental: 30mg LY2349821 [bDMARD-naive population] 30mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Biological: LY2439821 subcutaneous Other Name: LY2439821
Experimental: 80mg LY2439821 [bDMARD-naive population] 80mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Biological: LY2439821 subcutaneous Other Name: LY2439821
Experimental: 180mg LY2439821[bDMARD-naive population] 180mg at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Biological: LY2439821 subcutaneous Other Name: LY2439821
Experimental: 80mg LY2439821 [TNFa-IR population] 80mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Biological: LY2439821 subcutaneous Other Name: LY2439821
Experimental: 180mg LY2439821 [TNFa-IR population] 180mg LY2439821 at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Biological: LY2439821 subcutaneous Other Name: LY2439821
Placebo Comparator: Placebo [bDMARD-naive population] Placebo at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Drug: Placebo subcutaneous Other Name: Placebo
Placebo Comparator: Placebo [TNFa-IR population] Placebo at Weeks 0, 1, 2, 4, 6, 8 and 10, followed by 160mg LY2439821 in Part B (optional) at Weeks 16, 18, 20 and every 4 weeks thereafter through Week 60.	Drug: Placebo subcutaneous Other Name: Placebo

Detailed Description:

Study I1F-MC-RHAK is a multicenter study in patients with active rheumatoid arthritis on concomitant conventional disease modifying anti-rheumatic drug (DMARD) therapy. The study is a Phase 2 study with 2 parts. Part A is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging design and Part B is an optional, open-label extension design. Two patient populations will be evaluated in this study: biologic disease modifying anti-rheumatic drug [bDMARD]-naive patients and tumor necrosis factor alpha-inadequate responder [TNFα-IR] patients. Patients in Part A receive multiple subcutaneous (SC) injections of LY2439821 (bDMARD-naive patients: 0 [placebo], 3, 10, 30, 80, or 180 mg; TNFα-IR patients: 0 [placebo], 80 or 180 mg) at Weeks 0, 1, 2, 4, 6, 8, and 10. Patients in Part B receive SC injections of LY2439821 160 mg at Weeks 16, 18, and 20, and every 4 weeks thereafter through Week 60. Patients who complete both Part A and B have a total study participation of up to approximately 72 to 84 weeks.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

You must be between the ages of 18 and 75
You must have active RA

Qualifications Specific to the bDMARD-naive Population:

You must be regularly using methotrexate (MTX) for at least 12 weeks before your participation in this study

Qualifications Specific to the TNFα-IR Population:

You must have been treated with at least 1 biologic TNFα inhibitor therapy and either had an insufficient response to at least 3 months of treatment OR have been intolerant of such treatment
You must be regularly using at least 1 conventional DMARD in a stable treatment regimen

Exclusion Criteria:

You are concomitantly using non-steroidal anti-inflammatory drugs (NSAIDS), unless you are on a stable dose within the last 2 weeks
You are a woman who is lactating or breast feeding
You have donated more than 300 mL of blood within the last month
You have received glucocorticoid administered by intra-articular, intramuscular, or intravenous (IV) injection or oral corticosteroids at an average daily dose of greater than 10 mg per day of prednisone or its equivalent within the last 4 weeks
You had surgery on a joint that is to be assessed in the study within 2 months of study enrollment, or will require such during the study
You have another serious disorder or illness
You suffered a serious bacterial infection (for example, pneumonia, cellulitis, or bone or joint infections) within the last 3 months
You have a history of uncontrolled high blood pressure
You have clinical laboratory test results at entry that are outside the normal reference range
You are an employee of the clinic or you are an immediate family member of an employee of the clinic. Immediate family member is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
You are currently participating in or were discontinued within the last 30 days from another clinical trial involving an investigational drug
If you are a woman and you could become pregnant during this study, you must talk to the study doctor about the birth control that you will use to avoid getting pregnant during the study.
If you are a post menopausal woman, you must be at least 45 years of age and have not menstruated for the last 12 months
If you are a woman between 40 and 45 years of age, test negative for pregnancy, and have not menstruated during the last 12 months only, you must have an additional blood test to see if you can participate.
If you are male, you must agree to reduce the risk of your female partner becoming pregnant during the study.

Exclusions Specific to the bDMARD-naive Population:

You have received any prior biologic DMARD therapy such as TNFα, IL-1, IL-6, T-cell, or B-cell targeted therapies
You have had an inadequate response to a minimum of 3 months of treatment with 5 or more conventional DMARDs (such as leflunomide, azathioprine, cyclosporine, etc)
You have used DMARDs other than MTX, hydroxychloroquine, or sulfasalazine within the last 8 weeks
You have used leflunomide within the last 12 weeks and have not received cholestyramine to speed up the elimination of leflunomide from your body.

Exclusions Specific to the TNFα-IR Population:

You are currently using or recently used a biologic DMARD or a biologic TNFα inhibitor therapy within specified periods
You have had a serious reaction to other biologic DMARDs that, in the study doctor's opinion, puts you at serious risk
You have used cyclosporine or any other immunosuppressive in the 8 weeks before your participation in this study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00966875

Show 75 Study Locations

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Director:

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT-5 hours, EST)

Eli Lilly and Company

More Information

No publications provided

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00966875 History of Changes
Other Study ID Numbers:	12061, I1F-MC-RHAK
Study First Received:	August 25, 2009
Last Updated:	September 12, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:

rheumatoid arthritis
RA

Additional relevant MeSH terms:

Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases

Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on February 09, 2012