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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00619905
• Date of registration: 08/02/2008
• Prospective Registration: No
• Primary sponsor: Novartis
• Public title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 in Patients With Rheumatoid Arthritis With Ongoing Treatment With Methotrexate
• Scientific 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.
• Date of first enrolment: December 2003
• Target sample size: 53
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00619905
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 1/Phase 2

Countries of recruitment

Germany, Netherlands, Switzerland

Contacts

• Name: Novartis
• Affiliation: Novartis investigator site

Key inclusion & exclusion 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-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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: ACZ885

Primary Outcome(s)

Adverse events and infections occurrence throughout the study. [Time Frame: throughout the study]

Presence of anti-ACZ885 antibodies in serum at baseline, Days 43, 71 and end of study (Day 113). [Time Frame: throughout the study]

Secondary Outcome(s)

Disease Activity Score (DAS) at baseline and Days 43 and 113. [Time Frame: throughout the study]

Serum concentrations of ACZ885 at each visit. [Time Frame: throughout the study]

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)] . [Time Frame: throughout the study]

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. [Time Frame: throughout the study]

Secondary ID(s)

CACZ885A2101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors