Clinical trial NCT00487825: Safety and Efficacy of Intravenous ACZ885 and Oral Methotrexate Therapy in Patients With Early Rheumatoid Arthritis
Official title: A 26-week, Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Response to Treatment (ACR50) and to Determine a Biomarker Profile in Responders to ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) Plus MTX as Compared to MTX Alone in Early Rheumatoid Arthritis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: ACR20, ACR50, ACZ885 (anti-interleukin-1beta monoclonal antibody), rheumatoid arthritis, methotrexate
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-06-19
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: 6, 14, and 26 weeks of treatment
Secondary outcomes:
measure: Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
timeFrame: At 6 weeks, 14 weeks, and 26 weeks
measure: Percentage of Participants Achieving a Good European League Against Rheumatism (EULAR) Response (Based on the Disease Activity Score (DAS28)) at 26 Weeks
timeFrame: At 26 weeks
measure: The Number of Participants in Clinical Remission Based on Disease Activity Score (DAS)28 and Simplified Disease Activity Index (SDAI)
timeFrame: At 6 weeks, 14 weeks and 24 weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rheumatology Associates of Northern Alabama (Dr. William Shergy)
state: Alabama
city: Tuscaloosa
country: United States
facility: Clinic for Rheumatic Diseases (Dr. Richard Jones, III)
state: Alabama
city: Paradise Valley
country: United States
facility: Arizona Arthritis and Rheumatology Research (Dr. Paul Caldron)
state: Arizona
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research (Dr. Steven Mathews)
state: Florida
city: South Miami
country: United States
facility: Center for Arthritis and Rheumatic Diseases (Dr. Michael Weitz)
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates, Incorporated (Dr. Elias Halpert)
state: Florida
city: Rockford
country: United States
facility: Rockford Orthopedic Associates (Dr. Richard Olson)
state: Illinois
city: Urbandale
country: United States
facility: Mercy Arthritis and Osteoporosis Center (Dr. Alan Braun)
state: Iowa
city: Richmond Heights
country: United States
facility: Clayton Medical Research (Dr. Iri Don)
state: Missouri
city: Omaha
country: United States
facility: Westroads Medical Group (Dr. William Palmer)
state: Nebraska
city: Reno
country: United States
facility: Arthritis Center of Reno (Dr. Malin Prupas)
state: Nevada
city: Tulsa
country: United States
facility: Oklahoma Center for Arthritis therapy and Research (Dr. James McKay)
state: Oklahoma
city: Austin
country: United States
facility: MetaClin Research, Incorporated (Dr. Paul Pickrell)
state: Texas
city: Carlton
country: United States
facility: John M. Joseph, MD (Dr. John Joseph)
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology, P.A. (Dr. Atul Singhal)
state: Texas
city: Arlington
country: United States
facility: Arthritis Clinic of Northern Virginia (Dr. Philip Kempf)
state: Virginia
city: Spokane
country: United States
facility: Arthritis Northwest Rheumatology, PLLC (Dr. Jeffrey Butler)
state: Washington
city: Brussels
country: Belgium
facility: Novartis Investigative site
city: Nuernberg
country: Germany
facility: Novartis investigative site
city: Milan
country: Italy
facility: Novartis investigative site
city: Arnhem
country: Netherlands
facility: Novartis Investigative site
city: Barcelona
country: Spain
facility: Novartis investigative site
Study officials:
affiliation: Investigative site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References: