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

NCT00487825 | Completed Phase 2 Results

• 1 other identifier: CACZ885A2204
• Study Type: interventional
• Target: 78
• Locations: 6 countries
• Sites: 22

Brief Summary

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)

Conditions

Rheumatoid Arthritis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Response to Intravenous Canakinumab and Oral Methotrexate (MTX) Compared to MTX Alone as Determined by 50% Improvement in Symptoms According to the American College of Rheumatology Criteria (ACR50)

  A patient was considered as improved according to the ACR50 criteria if she/he had at least a 50 % improvement in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein (hsCRP))

  6, 14, and 26 weeks of treatment

Secondary Outcomes (3)

• Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone

  At 6 weeks, 14 weeks, and 26 weeks

• Percentage of Participants Achieving a Good European League Against Rheumatism (EULAR) Response (Based on the Disease Activity Score (DAS28)) at 26 Weeks

  At 26 weeks

• The Number of Participants in Clinical Remission Based on Disease Activity Score (DAS)28 and Simplified Disease Activity Index (SDAI)

  At 6 weeks, 14 weeks and 24 weeks

Study Arms (2)

Canakinumab + Methotrexate

EXPERIMENTAL

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.

Drug: Canakinumab (investigational); Drug: Methotrexate (MTX)

Methotrexate + placebo

ACTIVE COMPARATOR

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.

Drug: Placebo; Drug: Methotrexate (MTX)

Interventions

Canakinumab (investigational) 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.

Also known as: ACZ885

Canakinumab + Methotrexate

Placebo 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 + placebo

Methotrexate (MTX) DRUG

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

Canakinumab + Methotrexate; Methotrexate + placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (22)

Rheumatology Associates of Northern Alabama (Dr. William Shergy)

Huntsville, Alabama, 35801, United States

Location

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

Tuscaloosa, Alabama, 35406, United States

Location

Arizona Arthritis and Rheumatology Research (Dr. Paul Caldron)

Paradise Valley, Arizona, 85253, United States

Location

Jacksonville Center for Clinical Research (Dr. Steven Mathews)

Jacksonville, Florida, 32216, United States

Location

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

South Miami, Florida, 33143, United States

Location

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

Tamarac, Florida, 33321, United States

Location

Rockford Orthopedic Associates (Dr. Richard Olson)

Rockford, Illinois, 61107, United States

Location

Mercy Arthritis and Osteoporosis Center (Dr. Alan Braun)

Urbandale, Iowa, 50322, United States

Location

Clayton Medical Research (Dr. Iri Don)

Richmond Heights, Missouri, 63117, United States

Location

Westroads Medical Group (Dr. William Palmer)

Omaha, Nebraska, 68114, United States

Location

Arthritis Center of Reno (Dr. Malin Prupas)

Reno, Nevada, 89502, United States

Location

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

Tulsa, Oklahoma, 74104, United States

Location

MetaClin Research, Incorporated (Dr. Paul Pickrell)

Austin, Texas, 78704, United States

Location

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

Carlton, Texas, 75007, United States

Location

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

Mesquite, Texas, 75150, United States

Location

Arthritis Clinic of Northern Virginia (Dr. Philip Kempf)

Arlington, Virginia, 22205, United States

Location

Arthritis Northwest Rheumatology, PLLC (Dr. Jeffrey Butler)

Spokane, Washington, 99204, United States

Location

Novartis Investigative site

Brussels, Belgium

Location

Novartis investigative site

Nuremberg, Germany

Location

Novartis investigative site

Milan, Italy

Location

Novartis Investigative site

Arnhem, Netherlands

Location

Novartis investigative site

Barcelona, Spain

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

canakinumab; Methotrexate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  Investigative site

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2007
• First Posted: June 19, 2007
• Study Start: March 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: August 1, 2012
• Results First Posted: May 6, 2011

Record last verified: 2012-07

Locations

BE (1); NL (1); DE (1); US (17); ES (1); IT (1)