Safety and Efficacy of ACZ885 in Adult Patients With Established Rheumatoid Arthritis

NCT00504595 | Completed Phase 2 Results

• 1 other identifier: CACZ885A2207
• Study Type: interventional
• Target: 80
• Locations: 4 countries
• Sites: 4

Brief Summary

This study was intended to assess the safety, efficacy, and response to treatment using the American College of Rheumatology (ACR) criteria of 20% improvement in symptoms (ACR20) and to investigate a potential biomarker profile in adult patients with established rheumatoid arthritis

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Response to Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA)

  At each post-dose visit, an ACR20 responder was defined as someone who achieved at least 20% improvement in the tender and the swollen 28-joint count, and 20% improvement 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 weeks and 12 weeks

Secondary Outcomes (2)

• Efficacy of ACZ885 by Assessing the Response to Treatment Using the Simple Disease Index (SDAI)

  6 weeks and 12 weeks

• Efficacy of ACZ885 (Canakinumab) by Assessing the Response to Treatment Using the Disease Activity Score (DAS28)

  6 weeks and 12 weeks

Study Arms (2)

ACZ885

EXPERIMENTAL

Healthy Volunteers: Single administration of 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1. Rheumatoid Arthritis (RA) Patients: Dose of 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.

Drug: ACZ885 (investigational)

Placebo

PLACEBO COMPARATOR

Healthy Volunteers: Single administration of 600 mg of Placebo Intravenous (IV) on Day 1. Rheumatoid Arthritis (RA) Patients: Dose of 600 mg of Placebo Intravenous (IV) on Day 1, Day 15, and Day 43.

Drug: Placebo

Interventions

ACZ885 (investigational) DRUG

The ACZ885 was supplied in 6 mL colorless glass vials each containing nominally 150 mg ACZ885 (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: Canakinumab

ACZ885

Placebo DRUG

Matching placebo of ACZ885 was supplied in the 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• RA patients:
• Male and female patients aged 18 - 75 years (inclusive).
• Body weight between 50 and 100 kg (inclusive).
• Post menopausal or surgically sterile female patients are allowed. Female patients of child-bearing potential may participate if they are already on a stable dose of methotrexate. Additional birth control details to be provided at screening. Male patients must use an effective contraception method during the study and at least for 2 months following the completion/discontinuation of the study.
• Diagnosis of RA, classified by American Rheumatism Association 1987 revised criteria. Disease duration of at least 6 months is essential.
• Functional status class I, II or III classified according to the American College of Rheumatology 1991 revised criteria.
• Active disease evaluation (≥ 6 tender and ≥ 6 swollen joints)
• Prior treatment with 1-3 disease-modifying anti-rheumatic drugs (DMARDs) - Patients should have failed at least 1 DMARD but should not be deemed "refractory to all therapies". It is expected that patients are on a current treatment with methotrexate ≤ 25 mg/week and with the current dose stable for at least 3 months, however patients who did not tolerate MTX may also be considered. All patients will take folic acid 1 mg daily, or 5 mg weekly post MTX dose, to minimize toxicity, according to local guidelines. In addition to methotrexate, patients may be on either a stable dose of non-steroidal anti-inflammatory drugs (NSAIDs) and/or a stable dose of oral corticosteroids (prednisone or equivalent ≤ 10 mg daily) for at least 4 weeks prior to randomization. Patients who failed any DMARDs will be allowed.
• Negative purified protein derivative (PPD) tuberculin skin test reaction (PPD 5 tuberculin units or as according to local standard practice).

You may not qualify if:

• RA patients:
• Previous treatment with anti-Tumor Necrosis Factor (TNF)-α or anti IL-1 therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate or tacrolimus. The following washout period will be required for such patients to be eligible to participate in the trial.
• months washout prior to screening for etanercept or adalimumab
• months washout prior to screening for infliximab
• months washout prior to screening for rituximab
• month washout prior to screening for cyclosporine, mycophenolate and tacrolimus.
• If patient has been discontinued from other DMARDs (disease modifying antirheumatic drugs) for lack of efficacy or toxicity, the patient should be at least 1 month off the agent.
• Patients with congestive heart failure, QT prolongation syndrome or poorly controlled diabetes mellitus. Patients with a history of QTc prolongation will be excluded.
• Patients who have received intra-articular or systemic corticosteroid injections having been required for treatment of acute RA flare (not being part of a regular therapeutic regimen) within 4 weeks prior to randomization.

Sponsors & Collaborators

• Novartis: lead

Study Sites (4)

Novartis Investigative site

Moscow, Russia

Location

Novartis investigative site

Barcelona, Spain

Location

Novartis Investigative site

Bern, Switzerland

Location

Novartis investigative site

Istanbul, Turkey (Türkiye)

Location

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

Study Officials

• Novartis

  Investigator 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: July 19, 2007
• First Posted: July 20, 2007
• Study Start: May 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: August 7, 2012
• Results First Posted: June 23, 2011

Record last verified: 2012-08

Locations

RU (1); TU (1); CH (1); ES (1)