A Rheumatoid Arthritis Study in Patients on a Background Treatment of Methotrexate(FLEX-M)

• Register: EUCTR
• Last refreshed on: 3 February 2014
• Main ID: EUCTR2010-022205-17-LT
• Date of registration: 28/12/2010
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Rheumatoid Arthritis Study in Patients on a Background Treatment of Methotrexate(FLEX-M)
• Scientific title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of LY2127399 in Patients with Moderate to Severe Rheumatoid Arthritis (RA) who had an Inadequate Response to Methotrexate Therapy (FLEX-M)
• Date of first enrolment: 01/04/2011
• Target sample size: 990
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022205-17
• 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 Number of treatment arms in the trial: 3

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, Colombia, Croatia, Hungary, India, Japan, Korea, Republic of, Lithuania, Malaysia, Mexico, New Zealand, Peru, Poland, Romania, Russian Federation, Slovakia, South Africa, Sri Lanka, Taiwan, Ukraine, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Eli Lilly

• Name: Clinical Trial Information
• Affiliation: Eli Lilly

Key inclusion & exclusion criteria

Inclusion criteria:
• Male and female patients aged =18 years of age with a diagnosis of moderately to severely active adult onset RA
• Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years
• Regular use of methotrexate (MTX) in the past 12 weeks, with the dose being stable during the past 8 weeks
• At least 8 tender and swollen joints
• At least one erosion of a hand or foot joint observed on an X-ray
• An abnormally high C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR)
• Positive for Rheumatoid Factor (RF) or Anti-cyclic citrullinated peptide (CCP) antibody
• Woman must not be pregnant, breastfeeding, or become pregnant during the study

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 886
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 104

Exclusion criteria:
• Use of unstable doses of non-steroidal inflammatory drugs (NSAIDS) in the past 6 weeks
• Steroid injection or intravenous (iv) infusion in the last 6 weeks
• Use of more than 10 mg/day of oral steroids in the last 6 weeks
• History of an inadequate response to a biologic disease-modifying anti-rheumatic drug (DMARD)
• History of a serious reaction to other biological DMARDs
• History of the use of rituximab or other B cell therapy
• Use of DMARDS other than MTX, hydroxychloroquine, or sulfasalazine within the last 8 weeks
• Use of leflunomide within the last 12 weeks (unless cholestyramine was used to speed up the elimination of leflunomide)
• Surgery on a joint or other major surgery less than 2 months ago, or plans to have joint surgery or major surgery during the study
• Active fibromyalgia, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, or other systemic inflammatory condition except RA
• Cervical cancer or squamous skin cancer within the past 3 years, or other cancer within the past 5 years
• Received a live vaccine received within the past 12 weeks (for example, vaccines for measles, mumps, rubella, and chicken pox, and nasal-spray flu vaccines)
• Hepatitis or HIV
• A serious bacterial infection (for example, pneumonia or cellulitis) within 3 months or a serious bone or joint infection within 6 months
• Symptoms of herpes zoster or herpes simplex within the last month
• Active or latent tuberculosis (TB)
• Current symptoms of a serious disorder or illness
• Use of an investigational drug within the last month
• History of the use of rituximab, any other B cell targeted biotherapy, or denosumab


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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 14.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: LY2127399
Product Code: LY2127399
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available
CAS Number: Not availabl
Current Sponsor code: LY2127399
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: LY2127399
Product Code: LY2127399
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available
CAS Number: Not availabl
Current Sponsor code: LY2127399
Other descriptive name: Not available
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objectives of this study are to demonstrate, in patients on background MTX therapy, the superiority of 120 mg LY2127399 every 4 weeks (Q4W) (LY A) or 90 mg LY2127399 every 2 weeks (Q2W) (LY B), each after a loading dose, compared to placebo as follows:

? American College of Rheumatology 20% response rates (ACR20) at Week 24
? Structural progression as measured by van der Heijde modified Total Sharp Score (mTSS) at Week 52
? Health Assessment Questionnaire-Disability Index (HAQ-DI) scores at Week 24.

Secondary Objective: The secondary objectives of the study are as follows:
• To demonstrate, in patients on background MTX therapy, the superiority of LY A or LY B compared to placebo over 52 weeks
• To evaluate structure (X-rays)
• To evaluate the safety and tolerability of LY A or LY B compared to placebo.
• To characterize the time course of change in absolute B cell counts, B cell subsets, and changes in serum Ig levels to treatment with LY2127399 versus placebo over 52 weeks.
• To characterize the population PK of LY2127399 and explore PK/ PD relationships with efficacy, safety and biomarker endpoints.
• To assess the potential development of anti LY2127399 antibodies and the impact on patient safety, efficacy, and PK of LY2127399.
Additional exploratory measures will be studied, including:
• To explore biomarkers that may be contained in serum, plasma, messenger ribonucleic acid (mRNA), and deoxyribonucleic acid (DNA) samples.

Timepoint(s) of evaluation of this end point: 100 weeks

Primary end point(s): • Percentage of patients with American College of Rheumatology 20% response (ACR20) at Week 24
• Change from baseline to Week 52 in van der Heijde modified Total Sharp Score (mTSS)
• Change from baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)
• Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response
• Change from baseline in Disease Activity Score C-Reactive Protein (DAS28-CRP)
• Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response
• Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain scores and summary scores
• Change from baseline in Brief Fatigue Inventory (BFI) individual items and impact score
• Change from baseline in duration of morning stiffness (minutes)
• Percentage of patients with Major Clinical Response (MCR) during 52 weeks
• Percentage of patients with change from baseline in mTSS less than or equal to 0
• Change from baseline in B cell subset counts
• Population Pharmacokinetics (PK)
• Percentage of patients developing anti-LY2127399 antibodies
• Change from baseline in Brief Pain Inventory Short Form (BPI-sf) individual items and interference scores
• Percentage of patients with structural inhibition at Week 52
• Change from baseline in mTSS
• Change from baseline in serum immunoglobulin (Ig) levels
• Change from baseline in joint space narrowing score and bone erosions score (components of mTSS)
• Mean percent improvement in ACR N
• Change from baseline in Tender Joint Count (68 joint count)
• Change from baseline in Swollen Joint Count (66 joint count)
• Change from baseline in Patient's Assessment of Pain (VAS)
• Change from baseline in Patient's Global Assessment of Disease Activity (VAS)
• Change from baseline in Physician's Global Assessment of Disease Activity (VAS)
• Change from baseline to Week 52 in HAQ-DI
• Change from baseline in absolute B cell counts
• Percentage of patients with ACR20 at Week 52
• Time to ACR20 response

Secondary Outcome(s)

Secondary end point(s): •Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response
•Change from baseline in Disease Activity Score C-Reactive Protein (DAS28-CRP)
•Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response
•Change from baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain scores and summary scores
•Change from baseline in Brief Fatigue Inventory (BFI) individual items and impact score
•Change from baseline in duration of morning stiffness (minutes)
•Percentage of patients with Major Clinical Response (MCR) during 52 weeks
•Percentage of patients with change from baseline in mTSS less than or equal to 0
•Change from baseline in B cell subset counts
•Population Pharmacokinetics (PK)
•Percentage of patients developing anti-LY2127399 antibodies
•Change from baseline in Brief Pain Inventory Short Form (BPI-sf) individual items and interference scores
•Percentage of patients with structural inhibition at Week 52
•Change from baseline in mTSS
•Change from baseline in serum immunoglobulin (Ig) levels
•Change from baseline in joint space narrowing score and bone erosions score (components of mTSS)
•Mean percent improvement in ACR N
•Change from baseline in Tender Joint Count (68 joint count)
•Change from baseline in Swollen Joint Count (66 joint count)
•Change from baseline in Patient's Assessment of Pain (VAS)
•Change from baseline in Patient's Global Assessment of Disease Activity (VAS)
•Change from baseline in Physician's Global Assessment of Disease Activity (VAS)
•Change from baseline to Week 52 in HAQ-DI
•Change from baseline in absolute B cell counts
•Percentage of patients with ACR20 at Week 52
•Time to ACR20 response
•Change from baseline in CRP

Timepoint(s) of evaluation of this end point: 100 weeks

Secondary ID(s)

H9B-MC-BCDM

2010-022205-17-HU

NCT01198002

Source(s) of Monetary Support

Eli Lilly and Company