Efficacy, Safety and Tolerability of ACZ885 in Patients With Active Rheumatoid Arthritis

NCT00424346 | Completed Phase 2 Results

• 3 other identifiers: CACZ885A2201CACZ885A2201E1CACZ885A2201E2
• Study Type: interventional
• Target: 274
• Locations: 6 countries
• Sites: 17

Brief Summary

The 12-week core study was designed to evaluate risk-benefit of three subcutaneous dose regimens of ACZ885, added on to stable methotrexate (MTX) therapy (greater than or equal to 7.5 mg/week), compared to placebo in patients with active rheumatoid arthritis (RA). The study investigated the magnitude of effect as well as onset of effect for the different dose regimens. The primary objective of the extension studies was to assess long-term safety and tolerability of canakinumab (ACZ885) in patients with active RA. CACZ885A2201E1 evaluated this objective in patients who had participated in the core study (CACZ885A2201) and CACZ885A2201E2 did the same in patients who completed the first extension study.

Conditions

Rheumatoid Arthritis

Keywords

Active Rheumatoid Arthritis; anti-interleukin-1beta monoclonal antibody; methotrexate

Outcome Measures

Primary Outcomes (5)

• Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12

  Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]); * 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 \[hsCRP\]). Details on each of these components are provided in Outcome Measures 10-16. Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

  Baseline and Week 12

• Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase

  Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * 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 \[hsCRP\]). Participants were considered as non-responders if they failed the ACR20 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

  Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124

• Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase

  Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * 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 \[hsCRP\]). Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

  Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124

• Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase

  Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale \[VAS\]) * 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 \[hsCRP\]). Participants were considered as non-responders if they failed the ACR70 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.

  Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124

• Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase

  The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) in mg/L; * Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6

  Baseline and Weeks 24, 72 and 112

Secondary Outcomes (25)

• Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8

  Baseline and Weeks 2, 4 and 8

• Percentage of American College of Rheumatology [ACR] 20 Criteria Responders

  Baseline and Weeks 2, 4, 8 and 12

• Percentage of American College of Rheumatology [ACR] 70 Criteria Responders

  Baseline and Weeks 2, 4, 8 and 12

• Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12

  Baseline and Week 12

• Change From Baseline in Swollen 28-joint Count

  Baseline and Weeks 2, 4, 8 and 12

Study Arms (4)

Canakinumab 600 mg IV + 300 mg q2wk

EXPERIMENTAL

Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.

Drug: Canakinumab

Canakinumab 300 mg q2wk

EXPERIMENTAL

Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.

Drug: Canakinumab

Canakinumab 150 mg q4wk

EXPERIMENTAL

Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.

Drug: Canakinumab

Placebo

PLACEBO COMPARATOR

Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.

Drug: Placebo

Interventions

Canakinumab DRUG

Also known as: ACZ885

Canakinumab 150 mg q4wk; Canakinumab 300 mg q2wk; Canakinumab 600 mg IV + 300 mg q2wk

Placebo DRUG

Placebo

Eligibility Criteria

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

You may not qualify if:

• CORE STUDY
• Cooperative male or non-pregnant, non-lactating female patients at least 18 years of age who signed an informed consent before the initiation of any study procedure.
• Diagnosis of rheumatoid arthritis (RA) classified by American College of Rheumatology (ACR) 1987 revised criteria and with symptoms for at least 3 months before randomization.
• Functional status class I, II or III classified according to the ACR 1991 revised criteria.
• Patients treated with methotrexate (MTX) at the maximum tolerated (≤25 mg/week) and stable dose of ≥7.5 mg/week for at least 12 weeks before randomization.
• Patients who had failed any disease-modifying antirheumatic drugs (DMARDs) (including biologic agents and any DMARD used in combination with MTX) were allowed.
• For patients with previous treatment of biological therapy, the following wash-out periods were required before randomization:
• days for Kineret™ (anakinra) - with a terminal half-life of 4 to 6 hours (s.c. route).
• weeks for Enbrel® (etanercept) - with a terminal half-life of 102 ± 30 hours (s.c.
• route).
• weeks for Remicade® (infliximab) - with a terminal half-life of 8.0-9. 5 days (intravenous (i.v.) infusion).
• weeks for Humira® (adalimumab) - with a terminal half-life of 10-20 days (average 2 weeks) (subcutaneous (s.c.) route).
• weeks for Orencia® (abatacept) - with a terminal half-life of 13.1 (8-25) days (i.v. infusion).
• weeks for any other biologic - or 10 half-lives, whichever was longer.
• Patients who took systemic corticosteroids had to be on a stable dose of ≤10 mg/d prednisone or equivalent for at least 4 weeks before randomization.

Sponsors & Collaborators

• Novartis: lead

Study Sites (17)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Sun Valley Arthritis Center, Ltd

Peoria, Arizona, 85381, United States

Location

Catalina Pointe Arthritis & Rheumatology Specialists

Tucson, Arizona, 85704, United States

Location

Arthritis Center

Palm Harbor, Florida, 34684, United States

Location

Arthritis Research of Florida, Inc.

Palm Harbor, Florida, 34684, United States

Location

The Arthritis Center

Springfield, Illinois, 62704, United States

Location

St. Louis Cener for Clinical Research

St Louis, Missouri, 63128, United States

Location

The Center for Rheumatology

Albany, New York, 12206, United States

Location

AAIR Research Center

Rochester, New York, 14618, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Tacoma Center for Arthritis Research

Tacoma, Washington, 98405, United States

Location

Novartis

Vienna, Austria

Location

Novartis

Vilvoorde, Belgium

Location

Novartis

Dorval, Quebec, Canada

Location

Novartis

Nuremberg, Germany

Location

Novartis

Barcelona, Spain

Location

Related Publications (1)

• Alten R, Gomez-Reino J, Durez P, Beaulieu A, Sebba A, Krammer G, Preiss R, Arulmani U, Widmer A, Gitton X, Kellner H. Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study. BMC Musculoskelet Disord. 2011 Jul 7;12:153. doi: 10.1186/1471-2474-12-153.

  PMID: 21736751 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

canakinumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

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: January 17, 2007
• First Posted: January 19, 2007
• Study Start: November 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: October 1, 2009
• Last Updated: February 10, 2014
• Results First Posted: June 19, 2013

Record last verified: 2013-06

Locations

DE (1); US (12); ES (1); BE (1); AU (1); CA (1)