Clinical trial NCT00714493: RESTART C0168Z05 Rheumatoid Arthritis Study
Official title: A Phase 4, Multicenter, Open-Label, Assessor-Blinded Switch Study of the Efficacy and Safety of Infliximab (REMICADE) in Patients With Active Rheumatoid Arthritis Who Are Responding Inadequately to Etanercept (ENBREL) or Adalimumab (HUMIRA).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
remicade
infliximab
Centocor
etanercept
enbrel
adalimumab
humira
restart
swollen joints
tender joints.
Lead sponsor: Centocor Ortho Biotech Services, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2008-07-14
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effectiveness of treatment in patients with active rheumatoid arthritis who are having an inadequate response to at least 3 months of treatment with etanercept or adalimumab in addition to methotrexate.

Detailed description: This is a Phase 4, multi center, open-label, assessor blinded, switch study of infliximab in patients with active rheumatoid arthritis who are receiving methotrexate and are having an inadequate response to their current treatment with etanercept or adalimumab. The last dose of etanercept must have been at least 1 week but not more than 2 weeks prior to the first infliximab study infusion. The last dose of adalimumab must have been administered at least 2 weeks but not more than 4 weeks prior to the first infliximab study infusion. The study will be conducted for 30 weeks and will include 200 patients. All eligible patients will receive 3 mg/kg infliximab infusions (drug given into a vein) at weeks 0, 2, and 6 and every 8 weeks thereafter, if they achieve a European League Against Rheumatism (EULAR) response on their current dose of infliximab. Patients who do not achieve a EULAR response will increase their dose from 3mg/kg to 5 mg/kg at week 14. Patients who do not achieve a EULAR response at week 22 will increase from either 3 mg/kg to 5 mg/kg or from 5mg/kg to 7 mg/kg. The last study infusion will take place at week 22. The last study visit for effectiveness evaluations will take place at week 26. A week 30 follow-up visit will be performed for adverse events and tuberculosis evaluations, health economics assessments, and review of concomitant medications. All patients who end the study early will be required to complete all assessments. Patients will receive 3 mg/kg infliximab infusions at weeks 0, 2, and 6. If patients achieve European League Against Rheumatism (EULAR) response, they will remain on their current dose. Patients who do not demonstrate a EULAR response will increase their infliximab dose from 3 mg/kg to 5 mg/kg at week 14. At week 22, patients will also increase their infliximab dose from 3 mg/kg to 5mg/kg or from 5 mg/kg to 7mg/kg if they do not demonstrate a EULAR response.

Eligibility criteria: Inclusion Criteria:

* Patients must have rheumatoid arthritis
* Patients must have greater than or equal to 6 tender joints and greater than or equal to 6 swollen joints
* Patients must have inadequate disease response to etanercept or adalimumab
* Patients must have received etanercept or adalimumab in combination with methotrexate for a minimum of at least 3 months prior to the screening visit. The last dose of etanercept must have been given at least 1 week but not more than 2 weeks prior to first infliximab infusion. The last dose of adalimumab must have been administered at least 2 weeks but not more than 4 weeks prior to first infliximab infusion.

Exclusion Criteria:

* Patients who have a history of latent or active TB
* Have inflammatory disease other than rheumatoid arthritis
* Have had a chronic or recurrent infectious disease.

Primary outcomes:
measure: Percent of Patients Who Achieved a EULAR (The European League Against Rheumatism) Response at Week 10
timeFrame: Week 10
Secondary outcomes:
measure: Percent of Patients Who Acheived EULAR Response at Week 10 and Maintained Through Week 26 Without Infliximab Dose Increase
timeFrame: Week 26
measure: Percent of Patients Who Achieved EULAR Response at Week 26, Regardless of EULAR Response Status at Weeks 10, 14, and 22, With or Without Dose Increase Prior to Week 26
timeFrame: Week 26
measure: Change From Baseline in Physical Function (HAQ)
timeFrame: Week 10
measure: Change From Baseline in Physical Function (HAQ)
timeFrame: Week 26
measure: Percent of Patients Who Achieved ACR20 at Week 10
timeFrame: Week 10
measure: Percent of Patients Who Achieved ACR20 at Weeks 26.
timeFrame: Week 26
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Paradise Valley
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Santa Monica
country: United States
state: California
city: Bridgeport
country: United States
state: Connecticut
city: Lewes
country: United States
state: Delaware
city: Boca Raton
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Tamarac
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Moline
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Lexington
country: United States
state: Kentucky
city: Wheaton
country: United States
state: Maryland
city: Saint Clair Shores
country: United States
state: Michigan
city: Eagan
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Springfield
country: United States
state: Missouri
city: Berkeley Heights
country: United States
state: New Jersey
city: Freehold
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Mayfield
country: United States
state: Ohio
city: Middleburg Heights
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Allentown
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Wexford
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Jackson
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Mesquite
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Burke
country: United States
state: Virginia
city: Reston
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Graz-Eggenberg
country: Austria
city: Wien
country: Austria
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: Toronto
country: Canada
state: Ontario
city: Hamilton Ontario
country: Canada
city: Helsinki
country: Finland
city: Bordeaux Cedex
country: France
city: Limoges
country: France
city: Montivilliers
country: France
city: Orleans
country: France
city: Frankfurt
country: Germany
city: Holdenfelde
country: Germany
city: Leipzig
country: Germany
city: Muenchen
country: Germany
city: München
country: Germany
city: Ratingen
country: Germany
city: Ashkelon
country: Israel
city: Beer Yaakov
country: Israel
city: Haifa
country: Israel
city: Kfar Saba
country: Israel
city: Ramat Gan
country: Israel
city: Rehovot
country: Israel
city: Tel-Aviv
country: Israel
city: Alkmaar
country: Netherlands
city: Madrid
country: Spain
city: Oviedo
country: Spain
city: Santiago De Compostela
country: Spain
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Wigan
country: United Kingdom
Study officials:
affiliation: Centocor Ortho Biotech Services, L.L.C.
name: Centocor Ortho Biotech Services, L.L.C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Fleischmann R, Goldman JA, Leirisalo-Repo M, Zanetakis E, El-Kadi H, Kellner H, Bolce R, DeHoratius R, Wang J, Decktor D. Infliximab efficacy in rheumatoid arthritis after an inadequate response to etanercept or adalimumab: results of a target-driven active switch study. Curr Med Res Opin. 2014 Nov;30(11):2139-49. doi: 10.1185/03007995.2014.942416. Epub 2014 Jul 30.