Track topics on Twitter Track topics that are important to you
Tumor necrosis factor (TNF) alpha is a pro-inflammatory cytokine playing a significant role in the pathogenesis of the spondyloarthropathies (SpA). Infliximab is a TNF alpha blocking monoclonal antibody efficacious and safe as treatment of adult-onset SpA.
In this study we will try to demonstrate that infliximab administered at 5mg/kg to patients with juvenile onset SpA over a period of 12 weeks will have more efficacy than placebo and that it will be well tolerated. At the end of this phase, patients will go into a 52-week open extension to demonstrate sustained efficacy, safety, and tolerability of infliximab We will include 34 patients with juvenile onset SpA unresponsive to standard treatment. Efficacy will be assessed by counting the number of actively inflamed joints and a number of other parameters.
Background Tumor necrosis factor (TNF) alpha is a pro-inflammatory cytokine playing a significant role in the pathogenesis of the spondyloarthropathies (SpA). Infliximab is a TNF alpha blocking monoclonal antibody efficacious and safe as treatment of adult-onset SpA.
Hypothesis Infliximab will reduce the number of joints with active arthritis and improve additional parameters of disease activity and functioning more significantly than placebo over 12 weeks. Infliximab will demonstrate sustained efficacy and its administration will be safe and well tolerated over 52 weeks.
Objectives To demonstrate superior clinical efficacy with infliximab administered at 5mg/kg compared with placebo, in juvenile onset SpA over a period of 12 weeks. To demonstrate sustained efficacy, safety, and tolerability of infliximab at 5 mg/kg over 52 weeks.
Study Design This is a two-phase study. First phase: 12-week, randomized, double-blind, placebo-controlled period to evaluate efficacy, safety, and tolerability of infliximab 5 mg/kg.
Thirty-four patients allocated and randomized to infliximab 5 mg/kg or placebo. Randomization: restricted by blocks of four and by stratification in two diagnostic categories (undifferentiated SpA and ankylosing spondylitis). Efficacy analysis: change of the primary efficacy measure and secondary measures on weeks 2, 6, and 12, and any visit of discontinuation compared to week 0 and compared to changes in the placebo group.
Patients completing the 1st phase and those discontinued due to lack of efficacy after week 6 will continue into the 2nd phase to complete a total of 52 weeks. The 2nd open-phase will demonstrate the sustained efficacy, safety, and tolerability of infliximab along 52 weeks (weeks 12, 18, 24, 30, 36, 42 and 48). Efficacy analysis will focus on the change of the primary efficacy measurement and secondary measures on each scheduled visits- and any discontinuation visit compared to week 0.
Safety Evaluation Safety evaluations will included a search for clinical serious and non-serious adverse events; blood cytology, hepatic function tests, blood chemistry, urinanalysis, antinuclear antibodies by immunofluorescence, anti-DNA antibodies, rheumatoid factor, and chest X-rays.
Statistical Analysis The primary analysis will follow the "intention to treat" model. The data of patients who have been prematurely discontinued from the study- since V2.0- will be included in the primary analysis. The comparison between infliximab and placebo will be sequential.
Double-blind phase: step-down analysis; changes from baseline will be computed from a time-weighted average of the responses across weeks 2, 4, and 6 -and any discontinuation visit. 95% confidence intervals to evaluate the magnitude of the difference between infliximab and placebo will be used.
Open phase: mean changes from baseline on the time weighted average of responses over the whole length of the study.
Statistical tests: parametric and non parametric to evaluate the inter and intragroupal differences; ANCOVA, Mann Whitney, Wilcoxon, t of student and x2.
Sample size: 17 patients per group, plus 2 patients per group because of loss, supposes an improvement in the study group of 60% to 90%, with a confidence level of 95% to 99% (two tails test) and a power of 80% to 90%, with improvement in the control group of only 10%. The basis of such calculations is indirect because there are no data about juvenile SpA; yet, data on adults treated with infliximab and children and teenagers treated with sulfasalazine compared to placebo exist.
Budget The project and protocol are the result of the initiative of the investigators who are the intellectual proprietaries of it. Schering Plough, owner of the patent of Infliximab (Remicade; Schering Plough), has accepted to finance the project.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Servicio de Reumatología, Hospital General de México
Hospital General de Mexico
Published on BioPortfolio: 2014-08-27T03:33:53-0400
The purpose of the study is to establish a Danish cohort of spondylarthropathy (SpA) patients who are being treated with TNFalfa blockers. By following the TNFalfa blocking treated patient...
The present study was designed to assess the efficacy of infliximab in a 2-period study : - An initial period with comparison of infliximab versus placebo and allowing the determi...
This is a randomized, double-blind, multi-center, placebo-controlled study with two parallel treatment groups (placebo and infliximab) in subjects with ankylosing spondylitis (AS) to evalu...
This study evaluates the effectiveness and safety of infliximab in the treatment of acute pancreatitis in adults. A third of participants will receive one single dose of infliximab via inf...
Patients from an ongoing observational study (P05319) who have a limited (adequate but less than optimal) response to infliximab will be randomized to either increase the frequency of infl...
To assess whether obesity may affect natural history of inflammatory bowel diseases (IBD), we conducted an individual participant data (IPD) pooled analysis of placebo arms, using data from clinical t...
Among immunosuppressive- and biologic-naïve patients with moderate to severely active Crohn's disease (CD), a higher proportion of those treated with the combination of infliximab and azathioprine ac...
The association between infliximab (IFX) and fecal calprotectin (FC) levels on one hand, and the clinical and endoscopic response of patients with inflammatory bowel disease on the other, is well esta...
Reactive testing has emerged as the new standard of care for managing loss of response to infliximab in inflammatory bowel disease (IBD). Recent data suggest that proactive infliximab monitoring is as...
Antidrug antibodies (ADAs) dramatically increase infliximab clearance and are responsible for underexposure to the drug, leading to treatment failure. This pilot study aimed at developing a population...
A chimeric monoclonal antibody to TNF ALPHA that is used in the treatment of RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; PSORIATIC ARTHRITIS and CROHN'S DISEASE.
Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
Heterogeneous group of arthritic diseases sharing clinical and radiologic features. They are associated with the HLA-B27 ANTIGEN and some with a triggering infection. Most involve the axial joints in the SPINE, particularly the SACROILIAC JOINT, but can also involve asymmetric peripheral joints. Subsets include ANKYLOSING SPONDYLITIS; REACTIVE ARTHRITIS; PSORIATIC ARTHRITIS; and others.
Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...
Cytokines include chemokines, lymphokines, and monokines. Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to...