A Study in Patients With Rheumatoid Arthritis (FLEX V)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01202773
First received: September 14, 2010
Last updated: April 14, 2014
Last verified: March 2014
  Purpose

The primary purpose of this study is to help answer if LY2127399 is safe and effective in the treatment of rheumatoid arthritis in patients with an inadequate response to one or more Tumor necrosis factor-alpha (TNF α) inhibitors.

This study is comprised of 2 periods:

Period 1 - 24 week blinded treatment

Period 2 - 48 week post treatment follow up


Condition Intervention Phase
Rheumatoid Arthritis
Drug: LY2127399
Drug: Placebo every 4 weeks
Drug: Placebo every 2 weeks
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official 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 One or More TNF-α Inhibitors (FLEX V)

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percentage of patients with American College of Rheumatology 20% response (ACR20) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of patients with American College of Rheumatology 50% (ACR50) and 70% (ACR70) response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Mean percent improvement in ACR-N [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Tender Joint Count (68 joint count) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Swollen Joint Count (66 joint count) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Patient's Assessment of Pain (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Patient's Global Assessment of Disease Activity (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Physician's Global Assessment of Disease Activity (VAS) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Disease Activity Score-C-Reactive Protein (DAS28-CRP) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients with DAS28-Based European League Against Rheumatism (EULAR) response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domain and summary scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Brief Fatigue Inventory (BFI) individual items and impact scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in Brief Pain Inventory Short Form (BPI-sf) individual items and interference scores [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in duration of morning stiffness (minutes) [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
  • Time to ACR20 response [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to 24 weeks in absolute B cell counts [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline to 24 weeks in serum immunoglobulin (Ig) levels [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
  • Population Pharmacokinetics (PK) [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients developing anti-LY2127399 antibodies [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline to 24 weeks in CRP [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 555
Study Start Date: January 2011
Study Completion Date: January 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 120 mg LY2127399

Given every 4 weeks for 24 weeks. Patients receive a 240mg loading dose when initiating treatment.

During the Treatment Period, for blinding purposes, patients will alternate injections of LY2127399 and injections of placebo every 2 weeks.

After 16 weeks, non-responders will receive 90 mg every 2 weeks.

Drug: LY2127399
Administered Subcutaneously
Drug: Placebo every 4 weeks
Administered Subcutaneously
Experimental: 90 mg LY2127399

Given every 2 weeks for 24 weeks. Patients receive a 180 mg loading dose when initiating treatment.

After 16 weeks, non-responders will continue to receive 90 mg every 2 weeks.

Drug: LY2127399
Administered Subcutaneously
Placebo Comparator: Placebo

Given every 2 weeks for 24 weeks, and then patients are randomized to receive one of the 2 doses of LY2127399.

After 16 weeks, non-responders will receive 90 mg every 2 weeks.

Drug: LY2127399
Administered Subcutaneously
Drug: Placebo every 2 weeks
Administered Subcutaneously

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years
  • At least 8 tender and swollen joints
  • 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
  • Previously treated with biologic TNF-α inhibitor therapy (infliximab, certolizumab, golimumab, etanercept, adalimumab) and stopped treatment due to insufficient efficacy or intolerance
  • Regular use of at least one conventional disease-modifying anti-rheumatic drug (DMARD), with a stable dose for at least 8 weeks prior to study start
  • Woman must not be pregnant, breastfeeding, or become pregnant during the study

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 a serious reaction to other biological DMARDs
  • Use of an oral calcineurin inhibitor (e.g., cyclosporin or tacrolimus) in the last 8 weeks
  • 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 human immunodeficiency virus (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01202773

  Show 201 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: NCT01202773     History of Changes
Other Study ID Numbers: 13732, H9B-MC-BCDV
Study First Received: September 14, 2010
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Argentina: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Brazil: National Health Surveillance Agency
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Greece: Ministry of Health and Welfare
Italy: The Italian Medicines Agency
Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Agency
Malaysia: Ministry of Health
Mexico: Secretaria de Salud
New Zealand: Medsafe
New Zealand: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: The Central Register of Clinical Trials
Spain: Agencia Española de Medicamentos y Productos Sanitarios
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan: Center for Drug Evaluation
Taiwan: Department of Health
Mexico: Federal Commission for Sanitary Risks Protection

Keywords provided by Eli Lilly and Company:
Rheumatoid Arthritis

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 July 29, 2014