A Study in Participants With Rheumatoid Arthritis (FLEX V)

Lilly

Status and phase: Terminated; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo Q4W; Drug: LY2127399; Drug: Placebo Q2W

Study type: Interventional

Funder types: Industry

Identifiers

NCT01202773

13732

H9B-MC-BCDV (Other Identifier)

Details and patient eligibility

About

The primary purpose of this study is to help answer if LY2127399 is safe and effective in the treatment of rheumatoid arthritis in participants 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

Enrollment: 456 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of 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 1 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 anti-inflammatory drugs (NSAIDS) in the past 6 weeks
• Steroid injection or intravenous (IV) infusion in the last 6 weeks
• Use of more than 10 milligrams/day (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 (for example, 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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456 participants in 3 patient groups, including a placebo group

120 milligrams (mg) LY2127399

Experimental group

Description:

Given every 4 weeks (Q4W) for 24 weeks. Participants receive a 240-mg loading dose when initiating treatment. During the Treatment Period, for blinding purposes, participants will alternate injections of LY2127399 and injections of placebo every 2 weeks (Q2W). At Week 16, responders will receive 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 24-week treatment period. At Week 16, non-responders (NR) will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.

Treatment:

Drug: LY2127399

Drug: Placebo Q4W

90 mg LY2127399

Experimental group

Description:

Given Q2W for 24 weeks. Participants receive a 180-mg loading dose when initiating treatment. At Week 16, both responders and NR will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.

Treatment:

Drug: LY2127399

Placebo

Placebo Comparator group

Description:

Given Q2W for 24 weeks. Participants receive 2 injections of placebo when initiating treatment. At Week 16, responders will receive 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 24-week treatment period. At Week 16, NR will receive a 180-mg loading dose of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 24-week treatment period.

Treatment:

Drug: LY2127399

Drug: Placebo Q2W