Rheumatoid ArthritisPhase 3NCT02373813
Study of Etanercept Monotherapy vs Methotrexate Monotherapy for Maintenance of Rheumatoid Arthritis Remission
A Phase 3 study testing etanercept pre-filled syringe subcutaneous injection, Oral methotrexate and Folic acid (non-investigational product) in people with Rheumatoid Arthritis, run by Amgen at 136 sites in 15 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- etanercept pre-filled syringe subcutaneous injection, Oral methotrexate and Folic acid (non-investigational product)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 371 participants
- Where
- 136 sitesin 15 countries
- Study dates
- 20 Feb 2015to 6 Dec 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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).
Who cannot join
- 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
Show all 16Show fewer
- 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)
- Any clinically significant change in the Part 1 eligibility criteria during the run-in period
- SDAI > 3.3 and ≤ 11 on two consecutive visits at least two weeks apart OR SDAI > 3.3 and ≤ 11 on two or more separate visits OR SDAI > 11 at any time during the run-in period
- Subject has a clinically significant laboratory abnormality during run-in period which in the opinion of the investigator poses a safety risk, will prevent the subject from completing the study, or will interfere with the interpretation of the study results during the run-in period.
- NOTE: Other inclusion/exclusion criteria may apply per protocol.
Trial locations and contacts
136 sites in 15 countries.
136 sites in 15 countries
United States74 sites
Research Site
Albuquerque, New Mexico, 87102
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Ann Arbor, Michigan, 48109
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Baton Rouge, Louisiana, 70809
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Birmingham, Alabama, 35205
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Birmingham, Alabama, 35294
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Blue Island, Illinois, 60406
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Boise, Idaho, 83702
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Brooklyn, New York, 11201
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Carrollton, Texas, 75007
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Charleston, South Carolina, 29406
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Charlotte, North Carolina, 28204
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Clifton, New Jersey, 07012
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Corpus Christi, Texas, 78404
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Cypress, Texas, 77429
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Danville, Virginia, 24541
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Detroit, Michigan, 48202
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Doral, Florida, 33126
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Duncansville, Pennsylvania, 16635
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Escondido, California, 92025
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Fontana, California, 92335
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Fort Lauderdale, Florida, 33309
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Freehold, New Jersey, 07728
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Gainesville, Florida, 32607
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Glendale, Arizona, 85306
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Grand Rapids, Michigan, 49546
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Granger, Indiana, 46530
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Great Neck, New York, 11021
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Greenville, North Carolina, 27834
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Hemet, California, 92543
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Huntington Beach, California, 92646
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Huntsville, Alabama, 35801
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Jackson, Tennessee, 38305
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Kalamazoo, Michigan, 49008
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Knoxville, Tennessee, 37909-1900
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La Jolla, California, 92037
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Lansing, Michigan, 48910
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Lansing, Michigan, 48917
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Lawrenceville, Georgia, 30046
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League City, Texas, 77573
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Meridian, Idaho, 83642
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Mesa, Arizona, 85202
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Miami, Florida, 33126
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Miami, Florida, 33144
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Murrieta, California, 92563
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New Orleans, Louisiana, 70121
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New York, New York, 10021
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Newark, New Jersey, 07103
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Oklahoma City, Oklahoma, 73103
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Orange, California, 92868
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Orangeburg, South Carolina, 29118
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Orlando, Florida, 32806
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Palm Harbor, Florida, 34684
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Pensacola, Florida, 32514
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Phoenix, Arizona, 85037
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Pittsburgh, Pennsylvania, 15224
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Plano, Texas, 75024
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Sacramento, California, 95817
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San Antonio, Texas, 78229
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Santa Maria, California, 93454-6945
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Scottsdale, Arizona, 85258
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Skokie, Illinois, 60076
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Springfield, Illinois, 62703
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Springfield, Missouri, 65807
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St Louis, Missouri, 63141
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St. Petersburg, Florida, 33705
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Tampa, Florida, 33613
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Torrance, California, 90502
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Tustin, California, 92780
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Victorville, California, 92395
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Webster, Texas, 77598
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West Hills, California, 91307
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Wheaton, Maryland, 20902
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Wynnewood, Pennsylvania, 19096
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Wyomissing, Pennsylvania, 19610
Spain8 sites
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A Coruña, Galicia, 15006
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Barcelona, Catalonia, 08026
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Bilbao, Basque Country, 48013
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El Palmar, Murcia, 30120
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Majadahonda, Madrid, 28222
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Salamanca, Castille and León, 37007
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Seville, Andalusia, 41009
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Valencia, Valencia, 46017
Canada7 sites
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Hamilton, Ontario, L8N 1Y2
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Montreal, Quebec, H2L 1S6
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Québec, Quebec, G1V 3M7
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Rimouski, Quebec, G5L 8W1
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Sydney, Nova Scotia, B1S 3N1
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Trois-Rivières, Quebec, G8Z 1Y2
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Winnipeg, Manitoba, R3N 0K6
Italy7 sites
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Bari, 70124
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Catania, 95124
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Florence, 50139
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Naples, 80131
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Reggio Emilia, 42123
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Roma, 00128
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Verona, 37126
Greece6 sites
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Athens, 11527
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Athens, 12462
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Athens, 14561
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Heraklion, 71110
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Thessaloniki, 54636
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Thessaloniki, 56429
Bulgaria5 sites
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Plovdiv, 4000
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Plovdiv, 4002
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Sofia, 1505
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Sofia, 1612
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Sofia, 1784
France5 sites
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Bordeaux, 33076
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Cahors, 46005
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Montpellier, 34295
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Orléans, 45067
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Paris, 75010
Germany5 sites
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Berlin, 14059
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Frankfurt am Main, 60590
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Hildesheim, 31134
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Leipzig, 04103
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Püttlingen, 66346
Mexico4 sites
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Chihuahua City, 31000
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Guadalajara, Jalisco, 44650
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Mexicali, Baja California Norte, 21100
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Monterrey, Nuevo León, 64020
Poland4 sites
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Bydgoszcz, 85-168
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Karwiany, 52-200
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Sopot, 81-759
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Stalowa Wola, 37-450
Portugal4 sites
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Coimbra, 3000-075
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Lisbon, 1050-034
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Lisbon, 1649-035
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Ponte de Lima, 4990-041
Hungary3 sites
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Budapest, 1023
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Budapest, 1036
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Veszprém, 8200
Czechia2 sites
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Prague, 128 50
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Uherské Hradiště, 686 01
About this study
Official title: A Randomized Withdrawal Double-blind Study of Etanercept Monotherapy Compared to Methotrexate Monotherapy for Maintenance of Remission in Subjects With Rheumatoid Arthritis
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- etanercept pre-filled syringe subcutaneous injection, Oral methotrexate, Placebo for etanercept subcutaneous injection, Placebo for methotrexate, Folic acid (non-investigational product)
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etanercept pre-filled syringe subcutaneous injectionDrug
Also called Enbrel, AMG916
etanercept for injection in pre-filled syringes
Oral methotrexateDrug
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.
Placebo for etanercept subcutaneous injectionDrug
etanercept placebo for injection in pre-filled syringes
Placebo for methotrexateDrug
methotrexate placebo capsules
Folic acid (non-investigational product)Dietary supplement
Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Open Label Run-In: Etanercept plus Methotrexate | Experimental | Etanercept 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. Receives: Drug: etanercept pre-filled syringe subcutaneous injection; Drug: Oral methotrexate; Dietary Supplement: Folic acid (non-investigational product) |
| Double-Blind Treatment: Methotrexate Monotherapy | Experimental | Oral 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). Receives: Drug: etanercept pre-filled syringe subcutaneous injection; Drug: Oral methotrexate; Drug: Placebo for etanercept subcutaneous injection; Dietary Supplement: Folic acid (non-investigational product) |
| Double-Blind Treatment: Etanercept Monotherapy | Experimental | Etanercept 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). Receives: Drug: etanercept pre-filled syringe subcutaneous injection; Drug: Oral methotrexate; Drug: Placebo for methotrexate; Dietary Supplement: Folic acid (non-investigational product) |
| Double-Blind Treatment: Etanercept plus Methotrexate | Experimental | Etanercept 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). Receives: Drug: etanercept pre-filled syringe subcutaneous injection; Drug: Oral methotrexate; Dietary Supplement: Folic acid (non-investigational product) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 48
Secondary outcomes (15)
Percentage of Participants With SDAI Remission (≤ 3.3) at Week 48: Etanercept and Methotrexate 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.
Measured: Week 48
SDAI Score at All Measured Timepoints
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.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in SDAI Score at All Measured Timepoints
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. A negative change from baseline indicates improvement.
Measured: 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
The DAS28-ESR is a modified composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, ESR in mm/hr, and a 100 mm VAS measuring the participant's general health, from 0 (best) to 100 (worst). DAS28-ESR scores range from 0 to 9.4, where higher scores represent higher disease activity.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in DAS28-ESR at All Measured Timepoints
The DAS28-ESR is a modified composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, ESR in mm/hr, and a 100 mm VAS measuring the participant's general health, from 0 (best) to 100 (worst). DAS28-ESR scores range from 0 to 9.4, where higher scores represent higher disease activity. A negative change from baseline indicates improvement.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Disease Activity Score (28 Joint) Using the C-Reactive Protein Formula (DAS28-CRP) at All Measured Timepoints
The DAS28-CRP is a composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, CRP in mg/L, and a 100 mm VAS measuring the participant's general health from 0 (best) to 100 (worst). DAS28-CRP scores range from 0 to 9.4, where higher scores represent higher disease activity.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in DAS28-CRP at All Measured Timepoints
The DAS28-CRP is a composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, CRP in mg/L, and a 100 mm VAS measuring the participant's general health from 0 (best) to 100 (worst). DAS28-CRP scores range from 0 to 9.4, where higher scores represent higher disease activity. A negative change from baseline indicates improvement.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Clinical Disease Activity Index (CDAI) at All Measured Timepoints
The CDAI 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, and Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable. The CDAI score ranges from 0 to 76, where a higher score represents worse disease.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in CDAI at All Measured Timepoints
The CDAI 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, and Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable. The CDAI score ranges from 0 to 76, where a higher score represents worse disease. A negative change from baseline indicates improvement.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With SDAI Remission (≤ 3.3) at All Measured Timepoints
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.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With Boolean Remission at All Measured Timepoints
A participant achieves Boolean remission (66/68-joint count) if all of the following criteria are met at a single timepoint:
- 68-joint tender joint count ≤ 1
- 66-joint swollen joint count ≤ 1
- CRP (mg/dL) ≤ 1
- Patient's Global Assessment of Disease Activity using a VAS (where 0=no arthritis activity at all and 10=worst arthritis activity imaginable) ≤ 1.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With Disease Worsening
Percentage of participants who fulfilled disease-worsening criteria for the first time is presented. Disease worsening is defined as any of the following:
- an SDAI > 3.3 and ≤ 11 during 2 consecutive visits at least 2 weeks apart
- SDAI > 3.3 and ≤ 11 on 3 or more separate visits
- SDAI > 11 after randomization.
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.
Measured: Baseline, Week 12, Week 24, Week 36 and Week 48
Time to Disease Worsening
Disease worsening is defined as any of the following:
- an SDAI > 3.3 and ≤ 11 during 2 consecutive visits at least 2 weeks apart
- SDAI > 3.3 and ≤ 11 on 3 or more separate visits
- SDAI > 11 after randomization.
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.
Measured: up to Week 48
Time to Recapture SDAI Remission After Starting Rescue Treatment
In participants who receive rescue treatment during the double-blind treatment period.
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.
Measured: Between rescue and remission or Week 48, whichever comes first.
Percentage of Participants Receiving Rescue Treatment Who Experienced SDAI Remission at Week 48
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.
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2015 (estimated)
- Study start20 Feb 2015
- Primary completion6 Dec 2019
- Study completion6 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 371 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02373813
- Sponsor's protocol ID
- 20110186
- Status last verified
- Jan 2023
- First submitted
- 12 Jan 2015
- Last updated
- 11 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
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.
PubMed 29224127Curtis 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.
PubMed 33205906Curtis 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.
PubMed 36459119Curtis 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.
PubMed 37061234
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Withdrawal Double-blind Study of Etanercept Monotherapy Compared to Methotrexate Monotherapy for Maintenance of Remission in Subjects With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT02373813
- Acronym / sponsor ID
- 20110186
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 371 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 20 Feb 2015 (actual)
- Primary completion
- 6 Dec 2019 (actual)
- Study completion
- 6 Dec 2019 (actual)
- First posted
- 27 Feb 2015 (estimated)
- Results
- Posted 19 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Open Label Run-In: Etanercept plus Methotrexate | Experimental | Drug: etanercept pre-filled syringe subcutaneous injection, Drug: Oral methotrexate, Dietary Supplement: Folic acid (non-investigational product)Etanercept 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 | Experimental | Drug: etanercept pre-filled syringe subcutaneous injection, Drug: Oral methotrexate, Drug: Placebo for etanercept subcutaneous injection, Dietary Supplement: Folic acid (non-investigational product)Oral 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 | Experimental | Drug: etanercept pre-filled syringe subcutaneous injection, Drug: Oral methotrexate, Drug: Placebo for methotrexate, Dietary Supplement: Folic acid (non-investigational product)Etanercept 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 | Experimental | Drug: etanercept pre-filled syringe subcutaneous injection, Drug: Oral methotrexate, Dietary Supplement: Folic acid (non-investigational product)Etanercept 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- SDAI ≤ 3.3 at run-in visit 3
Key exclusion criteria (16 listed)
- 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:
- Any clinically significant change in the Part 1 eligibility criteria during the run-in period
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| etanercept pre-filled syringe subcutaneous injectionAlso: Enbrel, AMG916etanercept for injection in pre-filled syringes | Drug | Double-Blind Treatment: Etanercept Monotherapy, Double-Blind Treatment: Etanercept plus Methotrexate, Double-Blind Treatment: Methotrexate Monotherapy, Open Label Run-In: Etanercept plus Methotrexate |
| Oral methotrexateDuring 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. | Drug | Double-Blind Treatment: Etanercept Monotherapy, Double-Blind Treatment: Etanercept plus Methotrexate, Double-Blind Treatment: Methotrexate Monotherapy, Open Label Run-In: Etanercept plus Methotrexate |
| Placebo for etanercept subcutaneous injectionetanercept placebo for injection in pre-filled syringes | Drug | Double-Blind Treatment: Methotrexate Monotherapy |
| Placebo for methotrexatemethotrexate placebo capsules | Drug | Double-Blind Treatment: Etanercept Monotherapy |
| Folic acid (non-investigational product)Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care. | Dietary supplement | Double-Blind Treatment: Etanercept Monotherapy, Double-Blind Treatment: Etanercept plus Methotrexate, Double-Blind Treatment: Methotrexate Monotherapy, Open Label Run-In: Etanercept plus Methotrexate |
Primary outcome
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission (≤ 3.3) at Week 48: Etanercept Monotherapy vs. Methotrexate Monotherapy
Time frame: Week 48
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.
15 secondary outcomes
Percentage of Participants With SDAI Remission (≤ 3.3) at Week 48: Etanercept and Methotrexate vs. Methotrexate Monotherapy
Time frame: Week 48
SDAI Score at All Measured Timepoints
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in SDAI Score at All Measured Timepoints
Time frame: 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
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in DAS28-ESR at All Measured Timepoints
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Disease Activity Score (28 Joint) Using the C-Reactive Protein Formula (DAS28-CRP) at All Measured Timepoints
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in DAS28-CRP at All Measured Timepoints
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Clinical Disease Activity Index (CDAI) at All Measured Timepoints
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in CDAI at All Measured Timepoints
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With SDAI Remission (≤ 3.3) at All Measured Timepoints
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With Boolean Remission at All Measured Timepoints
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With Disease Worsening
Time frame: Baseline, Week 12, Week 24, Week 36 and Week 48
Time to Disease Worsening
Time frame: up to Week 48
Time to Recapture SDAI Remission After Starting Rescue Treatment
Time frame: Between rescue and remission or Week 48, whichever comes first.
Percentage of Participants Receiving Rescue Treatment Who Experienced SDAI Remission at Week 48
Time frame: Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29224127Curtis 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.
- Background: PubMed 33205906Curtis 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.
- Background: PubMed 36459119Curtis 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.
- Derived from this study: PubMed 37061234Curtis 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
136 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing etanercept pre-filled syringe subcutaneous injection, Oral methotrexate and Folic acid (non-investigational product) in people with Rheumatoid Arthritis, run by Amgen at 136 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 136 sites in United States, Spain, Canada, Italy, Greece and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission (≤ 3.3) at Week 48: Etanercept Monotherapy vs. Methotrexate Monotherapy (time frame: Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02373813, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2023.