Efficacy, Safety, and Tolerability Study of Infliximab in Juvenile Spondyloarthropathies

January 16, 2008 updated by: Hospital General de Mexico

Efficacy, Safety, and Tolerability of Infliximab (Remicade; Schering-Plough) in Juvenile Spondyloarthropathies: a Three-Month, Randomized, Double-Blind, Placebo-Controlled Trial and 52-Week Open Extension.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • DF
      • México City, DF, Mexico, 06720
        • Servicio de Reumatología, Hospital General de México

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ages less tha 16 years at symptoms onset and less than 18 years at entry
  • SpA diagnoses (ESSG criteria)
  • Active arthritis at least 2 peripheral joints
  • Pressure tenderness at least 3 peripheral entheses
  • Pain intensity of 40 mm in an analogue visual scale (VAS)
  • Lack of response to NSAID, sulfasalazine or methotrexate
  • Serum HCG-beta levels congruent with no pregnancy
  • Use of double-barrier contraceptive methods
  • History of BCG vaccination
  • Capacity to understand the study and follow protocol instructions
  • Written and signed consent letter.

Exclusion criteria:

  • Pregnancy and lactation
  • Mental disability
  • Functional class IV
  • Psoriasis, reactive arthritis or inflammatory bowel disease
  • Infectious, neoplastic, metabolic, hepatic, hematological, vascular, cardiopulmonary or renal active diseases
  • Opportunistic infectious
  • Active tuberculosis
  • Significant laboratory tests abnormalities
  • Current prednisone dose of more than 10 mg/day;
  • Intraarticular/muscular/venous glucocorticoids
  • Previous use of Infliximab or etanercept, pentoxyphylline, thalidomide, or anti-CD4 antibodies
  • Allergy or hypersensitivity to infliximab
  • Significant drug changes within one month before screening
  • Use of recreational drugs/illicit substances.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: B
Placebo
Drug: Placebo
Placebo -powder diluted in 250 ml of isotonic solution of sodium chloride- will be administered on weeks 0, 2 and 6.
Experimental: A
Infliximab
Drug: infliximab
Infliximab 5mg/kg diluted in 250 ml of isotonic solution of sodium chloride will be administered by the intravenous route on weeks 0, 2, 6, 12, 18, 24, 30, 36, 42, and 48.
Other Names:
  • remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of joints with active arthritis.
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of tender entheses; patient assessment of pain; patient/parent assessment of well being; investigator assessments of disease activity and health status; childhood health assessment questionnaire; and C reactive protein. Safety issues
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital General de Mexico

Collaborators

Schering-Plough

Investigators

  • Principal Investigator: Rubén Burgos-Vargas, MD, Rheumatologist, Hospital General de México/Professor of Medicine, Universidad Nacional Autónoma de México

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2002

Primary Completion (Actual)

June 1, 2007

Study Completion (Actual)

September 1, 2007

Study Registration Dates

First Submitted

December 31, 2007

First Submitted That Met QC Criteria

January 10, 2008

First Posted (Estimate)

January 11, 2008

Study Record Updates

Last Update Posted (Estimate)

January 17, 2008

Last Update Submitted That Met QC Criteria

January 16, 2008

Last Verified

December 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HGMREUMA.001.2007
  • DIC/02/404-B/02/036

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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