Safety and Efficacy of Intravenous ACZ885 and Oral Methotrexate Therapy in Patients With Early Rheumatoid Arthritis

NCT ID: NCT00487825

Last Updated: 2012-08-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2008-12-31

Brief Summary

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This study was intended to evaluate the safety and efficacy of intravenous (IV) ACZ885 and oral methotrexate (MTX) therapy in patients with early rheumatoid arthritis (RA)

Detailed Description

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Conditions

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Rheumatoid Arthritis

Keywords

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ACR20, ACR50, ACZ885 (anti-interleukin-1beta monoclonal antibody), rheumatoid arthritis, methotrexate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Canakinumab + Methotrexate

Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. MTX was given as variable dosing regimen of 7.5 mg-15 mg weekly.

Group Type EXPERIMENTAL

Canakinumab (investigational)

Intervention Type DRUG

Canakinumab was supplied in 6 mL colorless glass vials each containing nominally 150 mg canakinumab (with 20% overfill). The vials were kept at 2-8°C. At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.

Methotrexate (MTX)

Intervention Type DRUG

Methotrexate (MTX) was supplied in tablet form, each of 2.5 mg strength.

Methotrexate + placebo

Methotrexate (MTX) was given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo was supplied in form of a lyophilized cake (Powder for Solution for Infusion). At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.

Methotrexate (MTX)

Intervention Type DRUG

Methotrexate (MTX) was supplied in tablet form, each of 2.5 mg strength.

Interventions

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Canakinumab (investigational)

Canakinumab was supplied in 6 mL colorless glass vials each containing nominally 150 mg canakinumab (with 20% overfill). The vials were kept at 2-8°C. At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.

Intervention Type DRUG

Placebo

Matching placebo was supplied in form of a lyophilized cake (Powder for Solution for Infusion). At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.

Intervention Type DRUG

Methotrexate (MTX)

Methotrexate (MTX) was supplied in tablet form, each of 2.5 mg strength.

Intervention Type DRUG

Other Intervention Names

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ACZ885

Eligibility Criteria

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Inclusion Criteria

* Male and female patients of 18 to 75 years of age (inclusive)
* Recent definite diagnosis of rheumatoid arthritis (RA) (\<3 years since diagnosis), classified by American Rheumatism Association 1987 revised criteria.
* Candidate for methotrexate (MTX) or biologic due to erosive arthritis, with no contraindications to such therapy, including:
* Negative tuberculin skin test reaction
* Normal chest X-ray (within the last year) prior to possibility of receiving MTX (r/o lung fibrosis).
* Active disease: at least 6 swollen and 6 painful tender joints of 28 joint count,
* Vital signs should be within the following ranges:
* 18-59 years of age: oral temperature between 35.0-37.5 °C systolic blood pressure, 90-140 mm Hg diastolic blood pressure, 50-90 mm Hg pulse rate, 40 - 90 beats per minute
* 60-75 years of age: oral temperature between 35.0-37.5 °C systolic blood pressure, 100-160 mm Hg diastolic blood pressure, 50-100 mm Hg pulse rate, 50 - 100 beats per minute
* Women of child-bearing potential willing to practice double-barrier contraception during the study for at least 3 months following last study drug administration. Postmenopausal women must have no regular menstrual bleeding for at least 1 year prior to inclusion. Surgically sterilized women at least 6 months prior to screening.

Male patients must be using a double-barrier local contraception and refrain from fathering a child in the 3 months following last study drug administration.

* Weight: at least 45 kg; body mass index (BMI) within the range of 18 to 34.
* Oral corticosteroids are permitted as long as patients are on a stable dose (up to 10 mg) for at least 4 weeks before study start.

Exclusion Criteria

* Unable to have Magnetic Resonance Imaging (MRI) of wrist.
* Patients with magnetizable metal parts/devices on and in the body that could interfere with the MRI
* Patients with an unstable active medical condition that could impair evaluation of study results.
* Previous treatment with biological therapy or MTX.
* Limited kidney function (creatinine clearance under 60 ml/min)
* Previous treatment with other disease-modifying anti-rheumatic drugs such as sulfasalazine, hydroxychloroquine within 4 weeks of screening.
* Corticosteroids injections into joints within 4 weeks prior to screening.
* Participation in any clinical investigation within 4 weeks prior to study start or longer if required by local regulations, and for any other limitation of participation based on local regulations.
* Blood donation or loss of \> 400 mL within 8 weeks before study start, or longer if required by local regulation.
* Significant illness within 2 weeks of study start.
* Past personal or family medical history of clinically significant ECG abnormalities or cardiac issues.
* History of:

* fainting, orthostatic hypotension, sinus arrhythmia asthma and chronic obstructive pulmonary disease, clinically significant drug allergy or urticaria, eczematous dermatitis, and/or known hypersensitivity to the study drug or drugs similar to the study drug.
* disease of the blood building system, serious or active infections, gastric ulcers.
* surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the patient in case of participation in the study.
* immunodeficiency diseases, including a positive Human Immunodeficiency Virus (HIV) (ELISA and Western blot) test result.
* positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
* drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis

Role: PRINCIPAL_INVESTIGATOR

Investigative site

Locations

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Rheumatology Associates of Northern Alabama (Dr. William Shergy)

Huntsville, Alabama, United States

Site Status

Clinic for Rheumatic Diseases (Dr. Richard Jones, III)

Tuscaloosa, Alabama, United States

Site Status

Arizona Arthritis and Rheumatology Research (Dr. Paul Caldron)

Paradise Valley, Arizona, United States

Site Status

Jacksonville Center for Clinical Research (Dr. Steven Mathews)

Jacksonville, Florida, United States

Site Status

Center for Arthritis and Rheumatic Diseases (Dr. Michael Weitz)

South Miami, Florida, United States

Site Status

West Broward Rheumatology Associates, Incorporated (Dr. Elias Halpert)

Tamarac, Florida, United States

Site Status

Rockford Orthopedic Associates (Dr. Richard Olson)

Rockford, Illinois, United States

Site Status

Mercy Arthritis and Osteoporosis Center (Dr. Alan Braun)

Urbandale, Iowa, United States

Site Status

Clayton Medical Research (Dr. Iri Don)

Richmond Heights, Missouri, United States

Site Status

Westroads Medical Group (Dr. William Palmer)

Omaha, Nebraska, United States

Site Status

Arthritis Center of Reno (Dr. Malin Prupas)

Reno, Nevada, United States

Site Status

Oklahoma Center for Arthritis therapy and Research (Dr. James McKay)

Tulsa, Oklahoma, United States

Site Status

MetaClin Research, Incorporated (Dr. Paul Pickrell)

Austin, Texas, United States

Site Status

John M. Joseph, MD (Dr. John Joseph)

Carlton, Texas, United States

Site Status

Southwest Rheumatology, P.A. (Dr. Atul Singhal)

Mesquite, Texas, United States

Site Status

Arthritis Clinic of Northern Virginia (Dr. Philip Kempf)

Arlington, Virginia, United States

Site Status

Arthritis Northwest Rheumatology, PLLC (Dr. Jeffrey Butler)

Spokane, Washington, United States

Site Status

Novartis Investigative site

Brussels, , Belgium

Site Status

Novartis investigative site

Nuremberg, , Germany

Site Status

Novartis investigative site

Milan, , Italy

Site Status

Novartis Investigative site

Arnhem, , Netherlands

Site Status

Novartis investigative site

Barcelona, , Spain

Site Status

Countries

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United States Belgium Germany Italy Netherlands Spain

Other Identifiers

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CACZ885A2204

Identifier Type: -

Identifier Source: org_study_id