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

Lilly

Status and phase: Terminated; Phase 3

Conditions: Rheumatoid Arthritis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01198002

H9B-MC-BCDM (Other Identifier)

CTRI/2011/07/001870 (Registry Identifier)

11352

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 while on a background treatment of methotrexate.

This study is comprised of 3 periods:

Period 1: 52-week blinded treatment

Period 2: additional 48-week unblinded treatment

Period 3: 48-week post-treatment follow-up

Enrollment: 1,041 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

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 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 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
• History of the use of rituximab, any other B cell targeted biotherapy, or denosumab

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,041 participants in 3 patient groups, including a placebo group

120 milligrams (mg) LY2127399

Experimental group

Description:

Given every 4 weeks (Q4W) for 100 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 Weeks 16 and 52, 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 100-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 100-week treatment period.

Treatment:

Drug: Methotrexate

Drug: Placebo Q4W

Drug: LY2127399

90 mg LY2127399

Experimental group

Description:

Given Q2W for 100 weeks. Participants receive a 180 mg loading dose when initiating treatment. At Weeks 16 and 52, responders will receive 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q4W for the rest of the 100-week treatment period. At Week 16, 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 100-week treatment period.

Treatment:

Drug: Methotrexate

Drug: LY2127399

Placebo

Placebo Comparator group

Description:

Given Q2W for 52 weeks. At Week 16, responders will receive 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the 52 weeks. At Week 52, responders are randomized to receive 1 of the 2 doses of LY2127399, with loading dose of 240 mg or 180 mg of LY2127399, followed by 120 mg of LY2127399 Q4W or 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period. At Week 16, NR will receive a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment:

Drug: Methotrexate

Drug: Placebo Q2W

Drug: LY2127399