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

Rheumatoid Arthritis Clinical Trial

Official title:

A 12-week, Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Response to Treatment (ACR20) and to Determine a Biomarker Profile in Adult Patients With Established Rheumatoid Arthritis Responding to ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) as Compared to Healthy Subjects Exposed to ACZ885

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00504595
• Other study ID #: CACZ885A2207
• Status: Completed
• Phase: Phase 2
• First received: July 19, 2007
• Last updated: August 2, 2012
• Start date: May 2007
• Est. completion date: September 2008

Study information

• Verified date: August 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

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).

Exclusion Criteria:

RA patients:

• Previous treatment with anti-Tumor Necrosis Factor (TNF)-a 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.

1. 2 months washout prior to screening for etanercept or adalimumab

2. 3 months washout prior to screening for infliximab

3. 3 months washout prior to screening for rituximab

4. 1 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.

• Exclusion criteria 2-6 of the Health Volunteer section also applies here.

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• ACZ885 (investigational)
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.
• Placebo
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.

Locations

Country	Name	City	State
Russian Federation	Novartis Investigative site	Moscow
Spain	Novartis investigative site	Barcelona
Switzerland	Novartis Investigative site	Bern
Turkey	Novartis investigative site	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

Russian Federation,  Spain,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Efficacy of ACZ885 by Assessing the Response to Treatment Using the Simple Disease Index (SDAI)	SDAI is derived by the number of swollen joints and tender joints using the 28-joint count (tender28 and swollen28). SDAI measures the high sensitivity C-reactive protein (hsCRP) level, patient's global disease activity (PGDA) and evaluator's global disease activity (EGDA). PGDA and EGDA are measured on a 100 mm Visual Analogue Scale (VAS), ranging from no arthritis activity to maximal arthritis activity. SDAI = tender28 + swollen28 + CRP + (PGDA/10) + (EGDA/10). Lower scores indicate less disease activity.	6 weeks and 12 weeks	No
Secondary	Efficacy of ACZ885 (Canakinumab) by Assessing the Response to Treatment Using the Disease Activity Score (DAS28)	DAS28 is derived by the number of swollen joints and tender joints using the 28-joint count (tender28 and swollen28). DAS28 measures the C-reactive protein (CRP) (in mg/L) and the patient's general health (GH). GH is measured on a 100 mm Visual Analogue Scale (VAS), ranging from no arthritis activity to maximal arthritis activity. DAS28 = 0.56*v(tender28) + 0.28*v(swollen28) + 0.36*log_e(CRP+1) + 0.014*PGDA + 0.96. Lower scores indicate less disease activity.	6 weeks and 12 weeks	No