Clinical trial NCT00619905: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Rheumatoid Arthritis With Ongoing Treatment With Methotrexate
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Anti-interleukin-1 beta
ACZ885
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-02-21
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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-α 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.

Primary outcomes:
measure: Adverse events and infections occurrence throughout the study.
timeFrame: throughout the study
measure: Presence of anti-ACZ885 antibodies in serum at baseline, Days 43, 71 and end of study (Day 113).
timeFrame: throughout the study
Secondary outcomes:
measure: 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)] .
timeFrame: throughout the study
measure: Disease Activity Score (DAS) at baseline and Days 43 and 113.
timeFrame: throughout the study
measure: 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.
timeFrame: throughout the study
measure: Serum concentrations of ACZ885 at each visit.
timeFrame: throughout the study
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novartis Investigator Site
city: Hamburg
country: Germany
facility: Novartis Investigator Site
city: Koeln
country: Germany
facility: Novartis Investigator Site
city: Leipzig
country: Germany
facility: Novartis Investigator Site
city: Munich
country: Germany
facility: Novartis Investigator Site
city: Ratingen
country: Germany
facility: Novartis Investigator Site
city: Leiden
country: Netherlands
facility: Novartis Investigator Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigator Site
city: Bern
country: Switzerland
facility: Novartis Investigator Site
city: Geneva
country: Switzerland
facility: Novartis Investigator Site
Study officials:
affiliation: Novartis investigator site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alten R, Gram H, Joosten LA, van den Berg WB, Sieper J, Wassenberg S, Burmester G, van Riel P, Diaz-Lorente M, Bruin GJ, Woodworth TG, Rordorf C, Batard Y, Wright AM, Jung T. The human anti-IL-1 beta monoclonal antibody ACZ885 is effective in joint inflammation models in mice and in a proof-of-concept study in patients with rheumatoid arthritis. Arthritis Res Ther. 2008;10(3):R67. doi: 10.1186/ar2438. Epub 2008 Jun 5.