Clinical trial NCT02373813: Study of Etanercept Monotherapy vs Methotrexate Monotherapy for Maintenance of Rheumatoid Arthritis Remission
Official title: A Randomized Withdrawal Double-blind Study of Etanercept Monotherapy Compared to Methotrexate Monotherapy for Maintenance of Remission in Subjects With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-02-27
Enrollment: 371
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria (Part 1, Run-In Period):

* 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.

Exclusion Criteria (Part 1, Run-In Period):

* 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)

Inclusion Criteria (Part 2, Treatment Period):

* 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).

Exclusion Criteria (Part 2, Treatment Period):

* 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.

Primary outcomes:
measure: Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission (≤ 3.3) at Week 48: Etanercept Monotherapy vs. Methotrexate Monotherapy
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With SDAI Remission (≤ 3.3) at Week 48: Etanercept and Methotrexate vs. Methotrexate Monotherapy
timeFrame: Week 48
measure: SDAI Score at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in SDAI Score at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Disease Activity Score (28 Joint) Calculated Using the Erythrocyte Sedimentation Rate Formula (DAS28-ESR) at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in DAS28-ESR at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Disease Activity Score (28 Joint) Using the C-Reactive Protein Formula (DAS28-CRP) at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in DAS28-CRP at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Clinical Disease Activity Index (CDAI) at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Change From Baseline in CDAI at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Percentage of Participants With SDAI Remission (≤ 3.3) at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Percentage of Participants With Boolean Remission at All Measured Timepoints
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Percentage of Participants With Disease Worsening
timeFrame: Baseline, Week 12, Week 24, Week 36 and Week 48
measure: Time to Disease Worsening
timeFrame: up to Week 48
measure: Time to Recapture SDAI Remission After Starting Rescue Treatment
timeFrame: Between rescue and remission or Week 48, whichever comes first.
measure: Percentage of Participants Receiving Rescue Treatment Who Experienced SDAI Remission at Week 48
timeFrame: Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Glendale
country: United States
facility: Research Site
state: Arizona
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Escondido
country: United States
facility: Research Site
state: California
city: Fontana
country: United States
facility: Research Site
state: California
city: Hemet
country: United States
facility: Research Site
state: California
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Murrieta
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: Santa Maria
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Tustin
country: United States
facility: Research Site
state: California
city: Victorville
country: United States
facility: Research Site
state: California
city: West Hills
country: United States
facility: Research Site
state: California
city: Doral
country: United States
facility: Research Site
state: Florida
city: Fort Lauderdale
country: United States
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state: Florida
city: Gainesville
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Orlando
country: United States
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state: Florida
city: Palm Harbor
country: United States
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state: Florida
city: Pensacola
country: United States
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state: Florida
city: Saint Petersburg
country: United States
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state: Florida
city: Tampa
country: United States
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state: Florida
city: Lawrenceville
country: United States
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state: Georgia
city: Boise
country: United States
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state: Idaho
city: Meridian
country: United States
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state: Idaho
city: Blue Island
country: United States
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state: Illinois
city: Skokie
country: United States
facility: Research Site
state: Illinois
city: Springfield
country: United States
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state: Illinois
city: Granger
country: United States
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state: Indiana
city: Baton Rouge
country: United States
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state: Louisiana
city: New Orleans
country: United States
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state: Louisiana
city: Wheaton
country: United States
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state: Maryland
city: Ann Arbor
country: United States
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state: Michigan
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Grand Rapids
country: United States
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state: Michigan
city: Kalamazoo
country: United States
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state: Michigan
city: Lansing
country: United States
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state: Michigan
city: Lansing
country: United States
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state: Michigan
city: Saint Louis
country: United States
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state: Missouri
city: Springfield
country: United States
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state: Missouri
city: Clifton
country: United States
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state: New Jersey
city: Freehold
country: United States
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state: New Jersey
city: Newark
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state: New Jersey
city: Albuquerque
country: United States
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state: New Mexico
city: Brooklyn
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state: New York
city: Great Neck
country: United States
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state: New York
city: New York
country: United States
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state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Greenville
country: United States
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state: North Carolina
city: Oklahoma City
country: United States
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state: Oklahoma
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Wynnewood
country: United States
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state: Pennsylvania
city: Wyomissing
country: United States
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state: Pennsylvania
city: Charleston
country: United States
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state: South Carolina
city: Orangeburg
country: United States
facility: Research Site
state: South Carolina
city: Jackson
country: United States
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state: Tennessee
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Carrollton
country: United States
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state: Texas
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: Cypress
country: United States
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state: Texas
city: League City
country: United States
facility: Research Site
state: Texas
city: Plano
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Webster
country: United States
facility: Research Site
state: Texas
city: Danville
country: United States
facility: Research Site
state: Virginia
city: Buenos Aires
country: Argentina
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: Sydney
country: Canada
facility: Research Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Rimouski
country: Canada
facility: Research Site
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Uherske Hradiste
country: Czechia
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Cahors Cedex
country: France
facility: Research Site
city: Montpellier cedex 05
country: France
facility: Research Site
city: Orleans cedex 2
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt am Main
country: Germany
facility: Research Site
city: Hildesheim
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Püttlingen
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Heraklion
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Veszprem
country: Hungary
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Mexicali
country: Mexico
facility: Research Site
state: Baja California Norte
city: Guadalajara
country: Mexico
facility: Research Site
state: Jalisco
city: Monterrey
country: Mexico
facility: Research Site
state: Nuevo León
city: Chihuahua
country: Mexico
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Karwiany
country: Poland
facility: Research Site
city: Sopot
country: Poland
facility: Research Site
city: Stalowa Wola
country: Poland
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Ponte de Lima
country: Portugal
facility: Research Site
city: Panorama
country: South Africa
facility: Research Site
state: Western Cape
city: Sevilla
country: Spain
facility: Research Site
state: Andalucía
city: Salamanca
country: Spain
facility: Research Site
state: Castilla León
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: A Coruña
country: Spain
facility: Research Site
state: Galicia
city: Majadahonda
country: Spain
facility: Research Site
state: Madrid
city: El Palmar
country: Spain
facility: Research Site
state: Murcia
city: Bilbao
country: Spain
facility: Research Site
state: País Vasco
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Curtis 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.
citation: Curtis 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.