Clinical trial NCT01185301: Study to Determine the Effects of Different Doses of Methotrexate (MTX) When Taken With Adalimumab in Subjects With Early Rheumatoid Arthritis (RA)
Official title: A Double-Blind, Randomized, Parallel-Arm, Multicenter Study to Determine the Dose Response of Methotrexate (MTX) in Combination Therapy With Adalimumab in Subjects With Early Rheumatoid Arthritis (CONCERTO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Early Rheumatoid Arthritis
Keywords: Arthritis
Erosion
Humira
Adalimumab
Injection
Rheumatoid
Methotrexate
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2010-08-19
Enrollment: 395
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 determine the effects of different doses of methotrexate (MTX) when taken with adalimumab in subjects with early rheumatoid arthritis (RA).


Eligibility criteria: Inclusion Criteria:

* Male and female subjects at least 18 years of age
* Subject has a diagnosis of Rheumatoid Arthritis (RA) as defined by either the 1987-revised American College of Rheumatology (ACR) classification criteria or the new ACR/ European League Against Rheumatism (EULAR) diagnostic criteria for RA 2010 and has a disease duration of less than 1 year from diagnosis by a licensed health care provider
* Subject must meet the following criteria:

  1. Disease Activity Score of C-reactive Protein (DAS28\[CRP\]) ≥ 3.2 (at the Baseline visit only)
  2. At least 6 swollen joints out of 66 assessed (at the Screening and Baseline visits)
  3. At least 8 tender joints out of 68 assessed (at the Screening and Baseline visits)
  4. C-reactive protein (CRP) ≥ 1.5 mg/dL (at the Screening visit only), or erythrocyte sedimentation rate (ESR) ≥ 28 mm/1h (at the Screening and Baseline visits)
  5. Fulfill at least one of the following three criteria: Rheumatoid Factor (RF) positive, have at least 1 bony erosion, anti-cyclic citrullinated peptide (anti-CCP) antibody positive
* Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening

Exclusion Criteria:

* Subject has previous exposure to any systemic biologic therapy including adalimumab
* Subject has been previously treated with greater than 1 disease modifying antirheumatic drugs (DMARDs) or with methotrexate (MTX)
* Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study)
* Subject has chronic arthritis diagnosed before age 17 years
* History of invasive infection (e.g., listeriosis and histoplasmosis), chronic or active Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis (TB)
* Hepatitis B virus: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the hepatitis B virus DNA (HBV DNA) polymerase chain reaction (PCR) qualitative test
* Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline visit
* Female subject who is pregnant or breast-feeding or considering becoming pregnant

Primary outcomes:
measure: Percentage of Participants With 28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) Low Disease Activity at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Percentage of Participants With DAS28(CRP) Remission at Week 26
timeFrame: Week 26
measure: Percentage of Participants With American College of Rheumatology (ACR) 20 Criteria Response at Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants With American College of Rheumatology (ACR) 50 Criteria Response at Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants With American College of Rheumatology (ACR) 70 Criteria Response at Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants With American College of Rheumatology (ACR) 90 Criteria Response at Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants With American College of Rheumatology (ACR) 100 Criteria Response at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ -0.22 at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants With No Radiographic Progression at Week 26
timeFrame: Baseline, Week 26
measure: Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Week 26
timeFrame: Week 26
measure: Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 26
timeFrame: Week 26
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Site Reference ID/Investigator# 38973
state: Alabama
city: Mesa
country: United States
facility: Site Reference ID/Investigator# 41962
state: Arizona
city: Phoenix
country: United States
facility: Site Reference ID/Investigator# 39260
state: Arizona
city: Little Rock
country: United States
facility: Site Reference ID/Investigator# 45323
state: Arkansas
city: Hemet
country: United States
facility: Site Reference ID/Investigator# 38912
state: California
city: Victorville
country: United States
facility: Site Reference ID/Investigator# 39673
state: California
city: Jacksonville
country: United States
facility: Site Reference ID/Investigator# 38909
state: Florida
city: Miami
country: United States
facility: Site Reference ID/Investigator# 40422
state: Florida
city: Sarasota
country: United States
facility: Site Reference ID/Investigator# 38910
state: Florida
city: Atlanta
country: United States
facility: Site Reference ID/Investigator# 44284
state: Georgia
city: Gainesville
country: United States
facility: Site Reference ID/Investigator# 38907
state: Georgia
city: Lawrenceville
country: United States
facility: Site Reference ID/Investigator# 38972
state: Georgia
city: Rock Island
country: United States
facility: Site Reference ID/Investigator# 39670
state: Illinois
city: Springfield
country: United States
facility: Site Reference ID/Investigator# 42282
state: Illinois
city: Wichita
country: United States
facility: Site Reference ID/Investigator# 38911
state: Kansas
city: Covington
country: United States
facility: Site Reference ID/Investigator# 39672
state: Louisiana
city: Omaha
country: United States
facility: Site Reference ID/Investigator# 42204
state: Nebraska
city: Clifton
country: United States
facility: Site Reference ID/Investigator# 40651
state: New Jersey
city: Freehold
country: United States
facility: Site Reference ID/Investigator# 41422
state: New Jersey
city: Bronx
country: United States
facility: Site Reference ID/Investigator# 41424
state: New York
city: Greenville
country: United States
facility: Site Reference ID/Investigator# 40463
state: North Carolina
city: Columbus
country: United States
facility: Site Reference ID/Investigator# 42202
state: Ohio
city: Norman
country: United States
facility: Site Reference ID/Investigator# 44282
state: Oklahoma
city: Duncansville
country: United States
facility: Site Reference ID/Investigator# 41423
state: Pennsylvania
city: Charleston
country: United States
facility: Site Reference ID/Investigator# 38971
state: South Carolina
city: Jackson
country: United States
facility: Site Reference ID/Investigator# 39666
state: Tennessee
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 39643
state: Texas
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 45325
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 52042
state: Texas
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 40602
state: Washington
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 44924
city: Buenos Aires
country: Argentina
facility: Site Reference ID/Investigator# 44926
city: Rosario, Santa Fe
country: Argentina
facility: Site Reference ID/Investigator# 44925
city: San Juan
country: Argentina
facility: Site Reference ID/Investigator# 47302
city: Graz
country: Austria
facility: Site Reference ID/Investigator# 44928
city: Vienna
country: Austria
facility: Site Reference ID/Investigator# 44930
city: Vienna
country: Austria
facility: Site Reference ID/Investigator# 44927
city: Brussels
country: Belgium
facility: Site Reference ID/Investigator# 44934
city: Genk
country: Belgium
facility: Site Reference ID/Investigator# 44935
city: Gilly
country: Belgium
facility: Site Reference ID/Investigator# 44933
city: Liege
country: Belgium
facility: Site Reference ID/Investigator# 44932
city: Edmonton
country: Canada
facility: Site Reference ID/Investigator# 43783
city: Winnipeg
country: Canada
facility: Site Reference ID/Investigator# 43782
city: Brno
country: Czech Republic
facility: Site Reference ID/Investigator# 44937
city: Ceske Budejovice
country: Czech Republic
facility: Site Reference ID/Investigator# 48962
city: Ostrava
country: Czech Republic
facility: Site Reference ID/Investigator# 44939
city: Prague 2
country: Czech Republic
facility: Site Reference ID/Investigator# 44936
city: Uherske Hradiste
country: Czech Republic
facility: Site Reference ID/Investigator# 44938
city: Zlin
country: Czech Republic
facility: Site Reference ID/Investigator# 48963
city: Berlin-Buch
country: Germany
facility: Site Reference ID/Investigator# 44945
city: Berlin
country: Germany
facility: Site Reference ID/Investigator# 44941
city: Munich
country: Germany
facility: Site Reference ID/Investigator# 44942
city: Ratingen
country: Germany
facility: Site Reference ID/Investigator# 44944
city: Zerbst
country: Germany
facility: Site Reference ID/Investigator# 44943
city: Bydgoszcz
country: Poland
facility: Site Reference ID/Investigator# 44946
city: Lodz
country: Poland
facility: Site Reference ID/Investigator# 44982
city: Torun
country: Poland
facility: Site Reference ID/Investigator# 46584
city: Warsaw
country: Poland
facility: Site Reference ID/Investigator# 44984
city: Warsaw
country: Poland
facility: Site Reference ID/Investigator# 44983
city: Caguas
country: Puerto Rico
facility: Site Reference ID/Investigator# 38975
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 40122
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 39693
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 38916
city: Vega Baja
country: Puerto Rico
facility: Site Reference ID/Investigator# 39692
city: A Coruna
country: Spain
facility: Site Reference ID/Investigator# 44947
city: Elche (Alicante)
country: Spain
facility: Site Reference ID/Investigator# 44987
city: Oviedo (Asturias)
country: Spain
facility: Site Reference ID/Investigator# 44948
city: Valencia
country: Spain
facility: Site Reference ID/Investigator# 47782
Study officials:
affiliation: AbbVie
name: Dawn Carlson, MD
role: STUDY_DIRECTOR
References:
citation: Goss SL, Klein CE, Jin Z, Locke CS, Rodila RC, Kupper H, Burmester GR, Awni WM. Methotrexate Dose in Patients With Early Rheumatoid Arthritis Impacts Methotrexate Polyglutamate Pharmacokinetics, Adalimumab Pharmacokinetics, and Efficacy: Pharmacokinetic and Exposure-response Analysis of the CONCERTO Trial. Clin Ther. 2018 Feb;40(2):309-319. doi: 10.1016/j.clinthera.2018.01.002.
citation: Burmester GR, Kaeley GS, Kavanaugh AF, Gabay C, MacCarter DK, Nash P, Takeuchi T, Goss SL, Rodila R, Chen K, Kupper H, Kalabic J. Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab. RMD Open. 2017 Sep 17;3(2):e000465. doi: 10.1136/rmdopen-2017-000465. eCollection 2017.
citation: Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.