Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Rheumatoid Arthritis With Ongoing Treatment With Methotrexate

Rheumatoid Arthritis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Cohort Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 (Anti-Interleukin-1Beta Monoclonal Antibody) in Patients With Active Rheumatoid Arthritis (RA) Despite Ongoing Treatment With Methotrexate (MTX) 15 mg or More Weekly for at Least 3 Months.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00619905
• Other study ID #: CACZ885A2101
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 8, 2008
• Last updated: February 8, 2008
• Start date: December 2003
• Est. completion date: August 2005

Study information

• Verified date: February 2008
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

This study assessed the long-term safety and tolerability of ACZ885 in patients with rheumatoid arthritis, as well as long-term efficacy, long-term preservation and/or improvement of joint structure and bone mineral density, and long term maintenance of health-related quality of life.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: August 2005
• Est. primary completion date: August 2005
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male and female patients aged 18.5 - 65/75 years (depending on the dose group).

• Diagnosis of rheumatoid arthritis (ACR 1987 revised classification for criteria for RA) with a disease duration of at least 6 months prior to randomization.

• Active disease at screening and baseline evaluation (same evaluator) ) with more than 6 tender and 6 swollen joints of 28 examined (including any effused joint) and either a) Westergren erythrocyte sedimentation (ESR) = 28 mm/hour, or b) CRP = 6 mg/L.

• Patients should have failed at least 1 DMARD in the past, but should not be deemed "refractory to all therapies"

• Patients should have a current treatment regimen of = 15 mg methotrexate/week and with the current dose stable for approximately 3 months.

• Patients were required to have an otherwise stable RA therapeutic regimen, consisting of either a stable dose of NSAIDs and/or a stable dose of oral corticosteroids (prednisone or equivalent < 10 mg daily) for at least 4 weeks prior to randomization.

Exclusion Criteria:

• Previous treatment with anti-TNF-a antibody therapy (or other biological therapy) within appropriate timeframe (considering the half life of the compound)

• 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 four weeks prior to randomization OR require narcotic analgesics other than those accepted by the investigator for analgesia (e.g., codeine, tramadol, dextropropoxyphene)

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, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• ACZ885

• ACZ885

Locations

Country	Name	City	State
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Hamburg
Germany	Novartis Investigator Site	Koeln
Germany	Novartis Investigator Site	Leipzig
Germany	Novartis Investigator Site	Munich
Germany	Novartis Investigator Site	Ratingen
Netherlands	Novartis Investigator Site	Leiden
Netherlands	Novartis Investigator Site	Nijmegen
Switzerland	Novartis Investigator Site	Bern
Switzerland	Novartis Investigator Site	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

Germany,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events and infections occurrence throughout the study.		throughout the study
Primary	Presence of anti-ACZ885 antibodies in serum at baseline, Days 43, 71 and end of study (Day 113).		throughout the study
Secondary	ACR response criteria [including joint counts, patient/investigator disease activity and pain assessment, acute phase reactants (ESR and CRP) and a Health Assessment Questionnaire (HAQ)] .		throughout the study
Secondary	Disease Activity Score (DAS) at baseline and Days 43 and 113.		throughout the study
Secondary	Quantification of IL-1B, IL-6, and C-reactive protein (CRP), matrix metalloproteinases (MMPs) 1 and 3, and c-telopeptide of Type I collagen (Crosslaps), at Week 7 versus baseline.		throughout the study
Secondary	Serum concentrations of ACZ885 at each visit.		throughout the study