Study to Determine the Effects of Different Doses of Methotrexate (MTX) When Taken With Adalimumab in Subjects With Early Rheumatoid Arthritis (RA)

NCT01185301 | Completed Phase 3 Results

• 2 other identifiers: M12-0732010-019514-24
• Study Type: interventional
• Target: 395
• Locations: 10 countries
• Sites: 68

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).

Conditions

Early Rheumatoid Arthritis

Keywords

Arthritis; Erosion; Humira; Adalimumab; Injection; Rheumatoid; Methotrexate

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With 28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) Low Disease Activity at Week 26

  Percentage of participants achieving low disease activity as defined by a clinical response (DAS28\[CRP\] \< 3.2). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score \>5.1 indicates high disease activity, a DAS28 score \<3.2 indicates low disease activity, and a DAS28 score \<2.6 indicates clinical remission.

  Week 26

Secondary Outcomes (12)

• Percentage of Participants With DAS28(CRP) Remission at Week 26

  Week 26

• Percentage of Participants With American College of Rheumatology (ACR) 20 Criteria Response at Week 26

  Baseline, Week 26

• Percentage of Participants With American College of Rheumatology (ACR) 50 Criteria Response at Week 26

  Baseline, Week 26

• Percentage of Participants With American College of Rheumatology (ACR) 70 Criteria Response at Week 26

  Baseline, Week 26

• Percentage of Participants With American College of Rheumatology (ACR) 90 Criteria Response at Week 26

  Baseline, Week 26

Study Arms (4)

ADA + 2.5 mg MTX

ACTIVE COMPARATOR

2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks

Biological: adalimumab; Drug: methotrexate

ADA + 5 mg MTX

ACTIVE COMPARATOR

5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks

Biological: adalimumab; Drug: methotrexate

ADA + 10 mg MTX

ACTIVE COMPARATOR

10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks

Biological: adalimumab; Drug: methotrexate

ADA + 20 mg MTX

ACTIVE COMPARATOR

MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks

Biological: adalimumab; Drug: methotrexate

Interventions

adalimumab BIOLOGICAL

Pre-filled syringe every other week

Also known as: Humira

ADA + 10 mg MTX; ADA + 2.5 mg MTX; ADA + 20 mg MTX; ADA + 5 mg MTX

methotrexate DRUG

weekly oral capsule dosing

ADA + 10 mg MTX; ADA + 2.5 mg MTX; ADA + 20 mg MTX; ADA + 5 mg MTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Disease Activity Score of C-reactive Protein (DAS28\[CRP\]) ≥ 3.2 (at the Baseline visit only)
• At least 6 swollen joints out of 66 assessed (at the Screening and Baseline visits)
• At least 8 tender joints out of 68 assessed (at the Screening and Baseline visits)
• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (68)

Site Reference ID/Investigator# 38973

Huntsville, Alabama, 35801, United States

Location

Site Reference ID/Investigator# 41962

Mesa, Arizona, 85202, United States

Location

Site Reference ID/Investigator# 39260

Phoenix, Arizona, 85031, United States

Location

Site Reference ID/Investigator# 45323

Little Rock, Arkansas, 72205, United States

Location

Site Reference ID/Investigator# 38912

Hemet, California, 92543, United States

Location

Site Reference ID/Investigator# 39673

Victorville, California, 92395, United States

Location

Site Reference ID/Investigator# 38909

Jacksonville, Florida, 32209, United States

Location

Site Reference ID/Investigator# 40422

Miami, Florida, 33169, United States

Location

Site Reference ID/Investigator# 38910

Sarasota, Florida, 34239, United States

Location

Site Reference ID/Investigator# 44284

Atlanta, Georgia, 30312, United States

Location

Site Reference ID/Investigator# 38907

Gainesville, Georgia, 30501, United States

Location

Site Reference ID/Investigator# 38972

Lawrenceville, Georgia, 30045, United States

Location

Site Reference ID/Investigator# 39670

Rock Island, Illinois, 61201, United States

Location

Site Reference ID/Investigator# 42282

Springfield, Illinois, 62704, United States

Location

Site Reference ID/Investigator# 38911

Wichita, Kansas, 67203, United States

Location

Site Reference ID/Investigator# 39672

Covington, Louisiana, 70433, United States

Location

Site Reference ID/Investigator# 42204

Omaha, Nebraska, 68114, United States

Location

Site Reference ID/Investigator# 40651

Clifton, New Jersey, 07012, United States

Location

Site Reference ID/Investigator# 41422

Freehold, New Jersey, 07728, United States

Location

Site Reference ID/Investigator# 41424

The Bronx, New York, 10467, United States

Location

Site Reference ID/Investigator# 40463

Greenville, North Carolina, 27834, United States

Location

Site Reference ID/Investigator# 42202

Columbus, Ohio, 43213, United States

Location

Site Reference ID/Investigator# 44282

Norman, Oklahoma, 73069, United States

Location

Site Reference ID/Investigator# 41423

Duncansville, Pennsylvania, 16635, United States

Location

Site Reference ID/Investigator# 38971

Charleston, South Carolina, 29406, United States

Location

Site Reference ID/Investigator# 39666

Jackson, Tennessee, 38305, United States

Location

Site Reference ID/Investigator# 39643

Dallas, Texas, 75231, United States

Location

Site Reference ID/Investigator# 45325

Dallas, Texas, 75246, United States

Location

Site Reference ID/Investigator# 52042

Houston, Texas, 77074, United States

Location

Site Reference ID/Investigator# 40602

Seattle, Washington, 98101, United States

Location

Site Reference ID/Investigator# 44924

Buenos Aires, C1055AAF, Argentina

Location

Site Reference ID/Investigator# 44926

Buenos Aires, C1425DTG, Argentina

Location

Site Reference ID/Investigator# 44925

Rosario, Santa Fe, S2000PBJ, Argentina

Location

Site Reference ID/Investigator# 47302

San Juan, J5402DIL, Argentina

Location

Site Reference ID/Investigator# 44928

Graz, 80360, Austria

Location

Site Reference ID/Investigator# 44930

Vienna, 1090, Austria

Location

Site Reference ID/Investigator# 44927

Vienna, 1100, Austria

Location

Site Reference ID/Investigator# 44934

Brussels, 1200, Belgium

Location

Site Reference ID/Investigator# 44935

Genk, 3600, Belgium

Location

Site Reference ID/Investigator# 44933

Gilly, 6060, Belgium

Location

Site Reference ID/Investigator# 44932

Liège, 4000, Belgium

Location

Site Reference ID/Investigator# 43783

Edmonton, T5M 0H4, Canada

Location

Site Reference ID/Investigator# 43782

Winnipeg, R3A 1M3, Canada

Location

Site Reference ID/Investigator# 44937

Brno, 63800, Czechia

Location

Site Reference ID/Investigator# 48962

České Budějovice, 37021, Czechia

Location

Site Reference ID/Investigator# 44939

Ostrava, 72200, Czechia

Location

Site Reference ID/Investigator# 44936

Prague, 128 50, Czechia

Location

Site Reference ID/Investigator# 44938

Uherské Hradiště, 686 01, Czechia

Location

Site Reference ID/Investigator# 48963

Zlín, 76001, Czechia

Location

Site Reference ID/Investigator# 44941

Berlin, 10117, Germany

Location

Site Reference ID/Investigator# 44945

Buch, 13125, Germany

Location

Site Reference ID/Investigator# 44942

Munich, 80336, Germany

Location

Site Reference ID/Investigator# 44944

Ratingen, 40882, Germany

Location

Site Reference ID/Investigator# 44943

Zerbst, 39261, Germany

Location

Site Reference ID/Investigator# 44946

Bydgoszcz, 85168, Poland

Location

Site Reference ID/Investigator# 44982

Lodz, 90-242, Poland

Location

Site Reference ID/Investigator# 46584

Torun, 87-100, Poland

Location

Site Reference ID/Investigator# 44984

Warsaw, 02-118, Poland

Location

Site Reference ID/Investigator# 44983

Warsaw, 02-256, Poland

Location

Site Reference ID/Investigator# 38975

Caguas, 00725, Puerto Rico

Location

Site Reference ID/Investigator# 40122

San Juan, 00906-6312, Puerto Rico

Location

Site Reference ID/Investigator# 39693

San Juan, 00936-5067, Puerto Rico

Location

Site Reference ID/Investigator# 38916

San Juan, 00936-8344, Puerto Rico

Location

Site Reference ID/Investigator# 39692

Vega Baja, 00693, Puerto Rico

Location

Site Reference ID/Investigator# 44947

A Coruña, 15006, Spain

Location

Site Reference ID/Investigator# 44987

Elche (Alicante), 03203, Spain

Location

Site Reference ID/Investigator# 44948

Oviedo (Asturias), 33006, Spain

Location

Site Reference ID/Investigator# 47782

Valencia, 46026, Spain

Location

Related Publications (3)

• 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.

  PMID: 29402521 DERIVED

• 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.

  PMID: 28955494 DERIVED

• 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.

  PMID: 27338778 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis

Interventions

Adalimumab; Methotrexate

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Dawn Carlson, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2010
• First Posted: August 19, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: November 15, 2013
• Results First Posted: November 15, 2013

Record last verified: 2013-09

Locations

BE (4); DE (5); PL (5); CA (2); ES (4); AR (4); CZ (6); AU (3); US (30); PR (5)