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

NCT ID: NCT01185301

Last Updated: 2013-11-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

395 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2012-09-30

Brief Summary

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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).

Detailed Description

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Conditions

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Early Rheumatoid Arthritis

Keywords

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Arthritis Erosion Humira Adalimumab Injection Rheumatoid Methotrexate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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ADA + 2.5 mg MTX

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

Group Type ACTIVE_COMPARATOR

adalimumab

Intervention Type BIOLOGICAL

Pre-filled syringe every other week

methotrexate

Intervention Type DRUG

weekly oral capsule dosing

ADA + 5 mg MTX

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

Group Type ACTIVE_COMPARATOR

adalimumab

Intervention Type BIOLOGICAL

Pre-filled syringe every other week

methotrexate

Intervention Type DRUG

weekly oral capsule dosing

ADA + 10 mg MTX

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

Group Type ACTIVE_COMPARATOR

adalimumab

Intervention Type BIOLOGICAL

Pre-filled syringe every other week

methotrexate

Intervention Type DRUG

weekly oral capsule dosing

ADA + 20 mg MTX

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

Group Type ACTIVE_COMPARATOR

adalimumab

Intervention Type BIOLOGICAL

Pre-filled syringe every other week

methotrexate

Intervention Type DRUG

weekly oral capsule dosing

Interventions

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adalimumab

Pre-filled syringe every other week

Intervention Type BIOLOGICAL

methotrexate

weekly oral capsule dosing

Intervention Type DRUG

Other Intervention Names

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Humira

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dawn Carlson, MD

Role: STUDY_DIRECTOR

AbbVie

Locations

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Site Reference ID/Investigator# 38973

Huntsville, Alabama, United States

Site Status

Site Reference ID/Investigator# 41962

Mesa, Arizona, United States

Site Status

Site Reference ID/Investigator# 39260

Phoenix, Arizona, United States

Site Status

Site Reference ID/Investigator# 45323

Little Rock, Arkansas, United States

Site Status

Site Reference ID/Investigator# 38912

Hemet, California, United States

Site Status

Site Reference ID/Investigator# 39673

Victorville, California, United States

Site Status

Site Reference ID/Investigator# 38909

Jacksonville, Florida, United States

Site Status

Site Reference ID/Investigator# 40422

Miami, Florida, United States

Site Status

Site Reference ID/Investigator# 38910

Sarasota, Florida, United States

Site Status

Site Reference ID/Investigator# 44284

Atlanta, Georgia, United States

Site Status

Site Reference ID/Investigator# 38907

Gainesville, Georgia, United States

Site Status

Site Reference ID/Investigator# 38972

Lawrenceville, Georgia, United States

Site Status

Site Reference ID/Investigator# 39670

Rock Island, Illinois, United States

Site Status

Site Reference ID/Investigator# 42282

Springfield, Illinois, United States

Site Status

Site Reference ID/Investigator# 38911

Wichita, Kansas, United States

Site Status

Site Reference ID/Investigator# 39672

Covington, Louisiana, United States

Site Status

Site Reference ID/Investigator# 42204

Omaha, Nebraska, United States

Site Status

Site Reference ID/Investigator# 40651

Clifton, New Jersey, United States

Site Status

Site Reference ID/Investigator# 41422

Freehold, New Jersey, United States

Site Status

Site Reference ID/Investigator# 41424

The Bronx, New York, United States

Site Status

Site Reference ID/Investigator# 40463

Greenville, North Carolina, United States

Site Status

Site Reference ID/Investigator# 42202

Columbus, Ohio, United States

Site Status

Site Reference ID/Investigator# 44282

Norman, Oklahoma, United States

Site Status

Site Reference ID/Investigator# 41423

Duncansville, Pennsylvania, United States

Site Status

Site Reference ID/Investigator# 38971

Charleston, South Carolina, United States

Site Status

Site Reference ID/Investigator# 39666

Jackson, Tennessee, United States

Site Status

Site Reference ID/Investigator# 39643

Dallas, Texas, United States

Site Status

Site Reference ID/Investigator# 45325

Dallas, Texas, United States

Site Status

Site Reference ID/Investigator# 52042

Houston, Texas, United States

Site Status

Site Reference ID/Investigator# 40602

Seattle, Washington, United States

Site Status

Site Reference ID/Investigator# 44924

Buenos Aires, , Argentina

Site Status

Site Reference ID/Investigator# 44926

Buenos Aires, , Argentina

Site Status

Site Reference ID/Investigator# 44925

Rosario, Santa Fe, , Argentina

Site Status

Site Reference ID/Investigator# 47302

San Juan, , Argentina

Site Status

Site Reference ID/Investigator# 44928

Graz, , Austria

Site Status

Site Reference ID/Investigator# 44930

Vienna, , Austria

Site Status

Site Reference ID/Investigator# 44927

Vienna, , Austria

Site Status

Site Reference ID/Investigator# 44934

Brussels, , Belgium

Site Status

Site Reference ID/Investigator# 44935

Genk, , Belgium

Site Status

Site Reference ID/Investigator# 44933

Gilly, , Belgium

Site Status

Site Reference ID/Investigator# 44932

Liège, , Belgium

Site Status

Site Reference ID/Investigator# 43783

Edmonton, , Canada

Site Status

Site Reference ID/Investigator# 43782

Winnipeg, , Canada

Site Status

Site Reference ID/Investigator# 44937

Brno, , Czechia

Site Status

Site Reference ID/Investigator# 48962

České Budějovice, , Czechia

Site Status

Site Reference ID/Investigator# 44939

Ostrava, , Czechia

Site Status

Site Reference ID/Investigator# 44936

Prague, , Czechia

Site Status

Site Reference ID/Investigator# 44938

Uherské Hradiště, , Czechia

Site Status

Site Reference ID/Investigator# 48963

Zlín, , Czechia

Site Status

Site Reference ID/Investigator# 44941

Berlin, , Germany

Site Status

Site Reference ID/Investigator# 44945

Buch, , Germany

Site Status

Site Reference ID/Investigator# 44942

Munich, , Germany

Site Status

Site Reference ID/Investigator# 44944

Ratingen, , Germany

Site Status

Site Reference ID/Investigator# 44943

Zerbst, , Germany

Site Status

Site Reference ID/Investigator# 44946

Bydgoszcz, , Poland

Site Status

Site Reference ID/Investigator# 44982

Lodz, , Poland

Site Status

Site Reference ID/Investigator# 46584

Torun, , Poland

Site Status

Site Reference ID/Investigator# 44984

Warsaw, , Poland

Site Status

Site Reference ID/Investigator# 44983

Warsaw, , Poland

Site Status

Site Reference ID/Investigator# 38975

Caguas, , Puerto Rico

Site Status

Site Reference ID/Investigator# 40122

San Juan, , Puerto Rico

Site Status

Site Reference ID/Investigator# 39693

San Juan, , Puerto Rico

Site Status

Site Reference ID/Investigator# 38916

San Juan, , Puerto Rico

Site Status

Site Reference ID/Investigator# 39692

Vega Baja, , Puerto Rico

Site Status

Site Reference ID/Investigator# 44947

A Coruña, , Spain

Site Status

Site Reference ID/Investigator# 44987

Elche (Alicante), , Spain

Site Status

Site Reference ID/Investigator# 44948

Oviedo (Asturias), , Spain

Site Status

Site Reference ID/Investigator# 47782

Valencia, , Spain

Site Status

Countries

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United States Argentina Austria Belgium Canada Czechia Germany Poland Puerto Rico Spain

References

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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.

Reference Type DERIVED
PMID: 29402521 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28955494 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27338778 (View on PubMed)

Related Links

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Other Identifiers

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2010-019514-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M12-073

Identifier Type: -

Identifier Source: org_study_id