Study of Etanercept Monotherapy vs Methotrexate Monotherapy for Maintenance of Rheumatoid Arthritis Remission
A Randomized Withdrawal Double-blind Study of Etanercept Monotherapy Compared to Methotrexate Monotherapy for Maintenance of Remission in Subjects With Rheumatoid Arthritis
1 other identifier
interventional
371
15 countries
136
Brief Summary
The purpose of this study is to evaluate the efficacy of etanercept monotherapy compared to methotrexate monotherapy on maintenance of remission in participants with rheumatoid arthritis (RA) who were on etanercept plus methotrexate therapy. This is a multicenter, randomized withdrawal, double-blind controlled study in participants with rheumatoid arthritis on etanercept plus methotrexate therapy who are in very good disease control for 6 months prior to study entry. The study will consist of a 30-day screening period, a 24-week open label run-in period, a 48-week double-blind treatment period and a 30-day safety follow-up period.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 rheumatoid-arthritis
Started Feb 2015
Longer than P75 for phase_3 rheumatoid-arthritis
136 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 12, 2015
CompletedStudy Start
First participant enrolled
February 20, 2015
CompletedFirst Posted
Study publicly available on registry
February 27, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 6, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 6, 2019
CompletedResults Posted
Study results publicly available
December 19, 2020
CompletedJanuary 11, 2023
January 1, 2023
4.8 years
January 12, 2015
November 24, 2020
January 9, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission (≤ 3.3) at Week 48: Etanercept Monotherapy vs. Methotrexate Monotherapy
The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.
Week 48
Secondary Outcomes (15)
Percentage of Participants With SDAI Remission (≤ 3.3) at Week 48: Etanercept and Methotrexate vs. Methotrexate Monotherapy
Week 48
SDAI Score at All Measured Timepoints
Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in SDAI Score at All Measured Timepoints
Baseline, Week 12, Week 24, Week 36 and Week 48
Disease Activity Score (28 Joint) Calculated Using the Erythrocyte Sedimentation Rate Formula (DAS28-ESR) at All Measured Timepoints
Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in DAS28-ESR at All Measured Timepoints
Baseline, Week 12, Week 24, Week 36 and Week 48
- +10 more secondary outcomes
Study Arms (4)
Open Label Run-In: Etanercept plus Methotrexate
EXPERIMENTALEtanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 24 weeks. Participants also receive folic acid as standard of care.
Double-Blind Treatment: Methotrexate Monotherapy
EXPERIMENTALOral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will initiate rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).
Double-Blind Treatment: Etanercept Monotherapy
EXPERIMENTALEtanercept 50 mg weekly by subcutaneous injection plus placebo for methotrexate for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will initiate rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).
Double-Blind Treatment: Etanercept plus Methotrexate
EXPERIMENTALEtanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will continue on the assigned treatments (as rescue treatment).
Interventions
etanercept for injection in pre-filled syringes
During the open-label run-in period, methotrexate will be provided as 2.5 mg tablets. During the double-blind treatment period, methotrexate will be provided as 2.5 mg capsules.
etanercept placebo for injection in pre-filled syringes
methotrexate placebo capsules
Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.
Eligibility Criteria
You may qualify if:
- Subjects must be adults with a history of moderate to severe rheumatoid arthritis;
- Subjects must be in very good rheumatoid arthritis disease control for ≥ 6 months and be in remission as defined by a Simplified Disease Activity Index ≤ 3.3 at screening and at the end of the run-in period.
- Subjects must be on etanercept 50 mg per week plus methotrexate therapy for ≥ 6 months prior to the start of the run-in period. The methotrexate dose must be 10 to 25 mg per week for ≥ 6 months prior to the start of the run-in period and the dose must be stable for ≥ 8 weeks prior to the start of the run-in period.
- Subject has no known history of active tuberculosis, and has a negative test for tuberculosis during screening.
You may not qualify if:
- Subject has used biologic disease modifying antirheumatic drug other than etanercept OR has used an oral janus kinase inhibitor ≤ 6 months prior to run-in visit 1
- Subject has any active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to run-in visit 1.
- Subject has known alcohol addiction or dependency or uses alcohol daily.
- Subject has one or more significant concurrent medical conditions per investigator judgment, including the following:
- poorly controlled diabetes
- chronic kidney disease stage IIIb, IV, or V
- symptomatic heart failure (New York Heart Association class II, III, or IV)
- myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization
- uncontrolled hypertension
- severe chronic pulmonary disease (eg, requiring oxygen therapy)
- multiple sclerosis or any other demyelinating disease
- major chronic inflammatory disease or connective tissue disease other than rheumatoid arthritis (eg, systemic lupus erythematosus with the exception of secondary Sjögren's syndrome)
- SDAI ≤ 3.3 at run-in visit 3
- Subject if female and not at least 2 years postmenopausal or history of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, has a negative urine pregnancy test at baseline (day 1).
- Any clinically significant change in the Part 1 eligibility criteria during the run-in period
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (136)
Research Site
Birmingham, Alabama, 35205, United States
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Birmingham, Alabama, 35294, United States
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Huntsville, Alabama, 35801, United States
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Glendale, Arizona, 85306, United States
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Mesa, Arizona, 85202, United States
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Phoenix, Arizona, 85037, United States
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Scottsdale, Arizona, 85258, United States
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Escondido, California, 92025, United States
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Fontana, California, 92335, United States
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Hemet, California, 92543, United States
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Huntington Beach, California, 92646, United States
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La Jolla, California, 92037, United States
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Murrieta, California, 92563, United States
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Orange, California, 92868, United States
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Sacramento, California, 95817, United States
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Santa Maria, California, 93454-6945, United States
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Torrance, California, 90502, United States
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Tustin, California, 92780, United States
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Victorville, California, 92395, United States
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West Hills, California, 91307, United States
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Doral, Florida, 33126, United States
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Fort Lauderdale, Florida, 33309, United States
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Gainesville, Florida, 32607, United States
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Miami, Florida, 33126, United States
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Miami, Florida, 33144, United States
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Orlando, Florida, 32806, United States
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Palm Harbor, Florida, 34684, United States
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Pensacola, Florida, 32514, United States
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St. Petersburg, Florida, 33705, United States
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Tampa, Florida, 33613, United States
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Lawrenceville, Georgia, 30046, United States
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Boise, Idaho, 83702, United States
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Meridian, Idaho, 83642, United States
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Blue Island, Illinois, 60406, United States
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Skokie, Illinois, 60076, United States
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Springfield, Illinois, 62703, United States
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Granger, Indiana, 46530, United States
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Baton Rouge, Louisiana, 70809, United States
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New Orleans, Louisiana, 70121, United States
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Wheaton, Maryland, 20902, United States
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Ann Arbor, Michigan, 48109, United States
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Detroit, Michigan, 48202, United States
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Grand Rapids, Michigan, 49546, United States
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Kalamazoo, Michigan, 49008, United States
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Lansing, Michigan, 48910, United States
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Lansing, Michigan, 48917, United States
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Springfield, Missouri, 65807, United States
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St Louis, Missouri, 63141, United States
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Clifton, New Jersey, 07012, United States
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Freehold, New Jersey, 07728, United States
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Newark, New Jersey, 07103, United States
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Albuquerque, New Mexico, 87102, United States
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Brooklyn, New York, 11201, United States
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Great Neck, New York, 11021, United States
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New York, New York, 10021, United States
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Charlotte, North Carolina, 28204, United States
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Greenville, North Carolina, 27834, United States
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Oklahoma City, Oklahoma, 73103, United States
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Duncansville, Pennsylvania, 16635, United States
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Pittsburgh, Pennsylvania, 15224, United States
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Wynnewood, Pennsylvania, 19096, United States
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Wyomissing, Pennsylvania, 19610, United States
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Charleston, South Carolina, 29406, United States
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Orangeburg, South Carolina, 29118, United States
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Jackson, Tennessee, 38305, United States
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Knoxville, Tennessee, 37909-1900, United States
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Carrollton, Texas, 75007, United States
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Corpus Christi, Texas, 78404, United States
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Cypress, Texas, 77429, United States
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League City, Texas, 77573, United States
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Plano, Texas, 75024, United States
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San Antonio, Texas, 78229, United States
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Webster, Texas, 77598, United States
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Danville, Virginia, 24541, United States
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Buenos Aires, 1425, Argentina
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Plovdiv, 4000, Bulgaria
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Plovdiv, 4002, Bulgaria
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Sofia, 1505, Bulgaria
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Sofia, 1612, Bulgaria
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Sofia, 1784, Bulgaria
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Winnipeg, Manitoba, R3N 0K6, Canada
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Sydney, Nova Scotia, B1S 3N1, Canada
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Hamilton, Ontario, L8N 1Y2, Canada
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Montreal, Quebec, H2L 1S6, Canada
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Québec, Quebec, G1V 3M7, Canada
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Rimouski, Quebec, G5L 8W1, Canada
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Trois-Rivières, Quebec, G8Z 1Y2, Canada
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Prague, 128 50, Czechia
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Uherské Hradiště, 686 01, Czechia
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Bordeaux, 33076, France
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Cahors, 46005, France
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Montpellier, 34295, France
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Orléans, 45067, France
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Paris, 75010, France
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Berlin, 14059, Germany
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Frankfurt am Main, 60590, Germany
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Hildesheim, 31134, Germany
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Leipzig, 04103, Germany
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Püttlingen, 66346, Germany
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Athens, 11527, Greece
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Athens, 12462, Greece
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Athens, 14561, Greece
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Heraklion, 71110, Greece
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Thessaloniki, 54636, Greece
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Thessaloniki, 56429, Greece
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Budapest, 1023, Hungary
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Budapest, 1036, Hungary
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Veszprém, 8200, Hungary
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Bari, 70124, Italy
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Catania, 95124, Italy
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Florence, 50139, Italy
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Napoli, 80131, Italy
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Reggio Emilia, 42123, Italy
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Roma, 00128, Italy
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Verona, 37126, Italy
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Mexicali, Baja California Norte, 21100, Mexico
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Guadalajara, Jalisco, 44650, Mexico
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Monterrey, Nuevo León, 64020, Mexico
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Chihuahua City, 31000, Mexico
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Bydgoszcz, 85-168, Poland
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Karwiany, 52-200, Poland
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Sopot, 81-759, Poland
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Stalowa Wola, 37-450, Poland
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Coimbra, 3000-075, Portugal
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Lisbon, 1050-034, Portugal
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Lisbon, 1649-035, Portugal
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Ponte de Lima, 4990-041, Portugal
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Panorama, Western Cape, 7500, South Africa
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Seville, Andalusia, 41009, Spain
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Bilbao, Basque Country, 48013, Spain
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Salamanca, Castille and León, 37007, Spain
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Barcelona, Catalonia, 08026, Spain
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A Coruña, Galicia, 15006, Spain
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Majadahonda, Madrid, 28222, Spain
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El Palmar, Murcia, 30120, Spain
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Valencia, Valencia, 46017, Spain
Related Publications (4)
Curtis JR, Trivedi M, Haraoui B, Emery P, Park GS, Collier DH, Aras GA, Chung J. Defining and characterizing sustained remission in patients with rheumatoid arthritis. Clin Rheumatol. 2018 Apr;37(4):885-893. doi: 10.1007/s10067-017-3923-z. Epub 2017 Dec 9.
PMID: 29224127BACKGROUNDCurtis JR, Emery P, Karis E, Haraoui B, Bykerk V, Yen PK, Kricorian G, Chung JB. Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission. Arthritis Rheumatol. 2021 May;73(5):759-768. doi: 10.1002/art.41589. Epub 2021 Mar 24.
PMID: 33205906BACKGROUNDCurtis JR, Stolshek B, Emery P, Haraoui B, Karis E, Kricorian G, Collier DH, Yen PK, Bykerk VP. Effects of Disease-Worsening Following Withdrawal of Etanercept or Methotrexate on Patient-Reported Outcomes in Patients With Rheumatoid Arthritis: Results From the SEAM-RA Trial. J Clin Rheumatol. 2023 Jan 1;29(1):16-22. doi: 10.1097/RHU.0000000000001893. Epub 2022 Oct 22.
PMID: 36459119BACKGROUNDCurtis JR, Emery P, Kricorian G, Yen PK, Collier DH, Bykerk V, Haraoui B. Factors Associated With Maintenance of Remission Following Change From Combination Therapy to Monotherapy in Patients With Rheumatoid Arthritis. J Rheumatol. 2023 Sep;50(9):1114-1120. doi: 10.3899/jrheum.2022-1008. Epub 2023 Apr 15.
PMID: 37061234DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Amgen Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 12, 2015
First Posted
February 27, 2015
Study Start
February 20, 2015
Primary Completion
December 6, 2019
Study Completion
December 6, 2019
Last Updated
January 11, 2023
Results First Posted
December 19, 2020
Record last verified: 2023-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study
- Access Criteria
- Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request