Efficacy and Safety of Etanercept in Active RA Despite Methotrexate Therapy in Japan

NCT00688103 | Completed Phase 4 Results DMC

• 1 other identifier: Etanercept-01
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 1

Brief Summary

Multi-center, parallel-group, randomized, open control study. All patients will be selected to two treatment groups.

1. 1.Etanercept alone treatment group (25mg, twice/week, s.c.)
2. 2.Etanercept combined with MTX group (25mg, twice/week, s.c.+MTX 6-8mg/week)

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• EULAR Good Response

  EULAR good response was defined as reaching, at least, low decease activity by the disease activity score of 28 joints (DAS28) and its improvement by \> 1.2. DAS28 is a quantitative composite measure of disease activity for rheumatoid arthritis, and DAS28 \< 3.2 is regarded as low disease activity.

  at 24 weeks

• ACR50 Response Rate

  ACR (American College of Rheumatology) 50 response is defined by the following definition of improvement: at least 50% improvement in tender and swollen joint counts and at least 50% improvement in 3 of the 5 remaining ACR-core set measures; patient and physician global assessments, pain, disability, and an acute phase reactant (erythrocyte sedimentation rate or C-reactive protein).

  at 24 weeks

• Radiographic Progression Defined by Change in Van Der Heijde-modified Total Sharp Score

  The van der Heijde-modifiedtotal Sharp score is the sum of scores for erosions and joint space narrowing. The minimum and maximum total scores are 0 and 448, respectively. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, \<50% of the original joint space; 3=general, \>50% of the original joint space or subluxation; 4=ankylosis.

  at 52 weeks

Study Arms (2)

ETN Alone

ACTIVE COMPARATOR

etanercept (25mg, twice/week, s.c.)

Drug: ETN Alone

ETN+MTX

ACTIVE COMPARATOR

etanercept (25mg, twice/week, s.c.) combined with methotrexate (6-8mg/week)

Drug: ETN+MTX

Interventions

ETN Alone DRUG

etanercept (25 mg, twice/week, s.c.)

Also known as: etanercept

ETN Alone

ETN+MTX DRUG

etanercept (25 mg, twice/week, s.c.) combined with methotrexate (6-8 mg/week)

Also known as: etanercept and methotrexate

ETN+MTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients had to be at least 18 years of age
• fulfilled the 1987 revised classification criteria for RA by in American College of Rheumatology (ACR)
• met the guidelines for the proper use of ETN in Japan (having at least 6 tender joints and 6 swollen joints
• either serum C-reactive protein more than 2 mg/dl or ESR no less than 28 mm at 1 hour, with adequate safety profiles)
• be ACR functional class I-III
• have been receiving MTX 6 mg/week for a minimum of 3 months at a stable dose for at least 4 weeks at the time of study enrollment

You may not qualify if:

• Patients who required concurrent use of prednisone (PSL) \>10 mg/day, or its equivalent, were excluded from study entry
• the start of dose increment of PSL equivalents within 3 months of the study enrollment
• experience of antirheumatic therapy except for MTX and PSL equivalents
• previous treatment with ETN or any other biological treatment

Sponsors & Collaborators

• Japan Biological Agent Study Integrated Consortium: lead

Study Sites (1)

Keio University

Tokyo, Tokyo, 160-8582, Japan

Location

Related Publications (3)

• Kameda H, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Takeuchi T; Japan Biological Agent Study Integrated Consortium. Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol. 2010 Dec;20(6):531-8. doi: 10.1007/s10165-010-0324-4. Epub 2010 Jun 24.

  PMID: 20574649 RESULT

• Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T. Continuation of methotrexate resulted in better clinical and radiographic outcomes than discontinuation upon starting etanercept in patients with rheumatoid arthritis: 52-week results from the JESMR study. J Rheumatol. 2011 Aug;38(8):1585-92. doi: 10.3899/jrheum.110014. Epub 2011 May 15.

  PMID: 21572151 RESULT

• Kameda H, Kanbe K, Sato E, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Yamanaka H, Takeuchi T; Japan Biological Agent Integrated Consortium (JBASIC). A merged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study. Ann Rheum Dis. 2013 Feb;72(2):310-2. doi: 10.1136/annrheumdis-2012-201804. Epub 2012 Sep 12. No abstract available.

  PMID: 22975754 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Etanercept; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Hideto Kameda
• Organization: School of Medicine, Toho University

hideto.kameda@med.toho-u.ac.jp

+81-3-3468-1251

Study Officials

• Tsutomu Takeuchi, MD, PhD

  JBASIC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Toho University

Study Record Dates

• First Submitted: May 25, 2008
• First Posted: June 2, 2008
• Study Start: June 1, 2005
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2010
• Last Updated: October 1, 2015
• Results First Posted: October 1, 2015

Record last verified: 2015-09

Locations

JP (1)