Five-Year Actively Controlled Clinical Trial in New Onset Juvenile Systemic Lupus Erythematosus Nephritis

March 19, 2018 updated by: Istituto Giannina Gaslini

Five-Year Single-Blind, Phase III Effectiveness Randomised Actively Controlled Clinical Trial in New Onset Juvenile Systemic Lupus Erythematosus Nephritis: Oral Cyclophosphamide Versus High Dose Intravenous Cyclophosphamide Versus Intermediate Dose Intravenous Cyclophosphamide

This is a 5-year project, involving 185 partners from 46 countries (110 in 21 EU States and 75 in 25 extra-EU States), with a randomised clinical trials (RCT) in juvenile systemic lupus erythematosus (JSLE): 5-year phase III single-blind, RCT in children with newly diagnosed, WHO class III, IV JSLE proliferative nephritis: PDN and oral cyclophosphamide (CYC) versus high dose intravenous (iv) CYC versus intermediate dose iv CYC, followed by maintenance with azathioprine.The trial is aimed to find out the treatment regimen associated with the lowest occurrence of flare and the lowest drug related toxicity.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Scientific objectives: The proposed project is aimed to improve treatment approaches for rare, severe and disabling paediatric rheumatic diseases (PRD). This goal will be achieved by the Paediatric Rheumatology International Trials Organisation (PRINTO) an international network whose main function is to provide a scientific base for current PRD treatments for which no evidence based data exist in the literature, and for drugs for which there is no support from industries.

This is a 5-year project, involving 185 partners from 46 countries (110 in 21 EU States and 75 in 25 extra-EU States), with a randomised clinical trials (RCT) in juvenile systemic lupus erythematosus (JSLE): 5-year phase III single-blind, RCT in children with newly diagnosed, WHO class III, IV JSLE proliferative nephritis: PDN and oral cyclophosphamide (CYC) versus high dose intravenous (iv) CYC versus intermediate dose iv CYC, followed by maintenance with azathioprine. The JSLE RCT is aimed to find out the treatment regimen associated with the lowest occurrence of flare and the lowest drug related toxicity. The retention on treatment will be used as main measure of effectiveness.

Methodology: The present protocol is the natural follow up of previous work conducted by PRINTO. In particular the RCT foreseen in this protocol is modelled after the successful completion of an early phase trial with MTX in juvenile idiopathic arthritis, and will use validated JSLE outcome measures for the evaluation of response to therapy.

It is the basic premise of this protocol that, without i) the involvement of the international paediatric rheumatology community, ii) the innovative type of mechanism described herein, these studies would never be conducted.

Objectives. The goals of the current protocol is therefore the natural follow-up of the objectives achieved with the previous grants and, in particular, of projects designed to discern new models for the successful conduct of clinical trials in children with rare diseases, and to develop standardized and validated measures for the evaluation of response to therapy in JSLE.

The proposed trials in in JSLE (oral cyclophosphamide [CYC] versus intermediate dose intravenous [iv] CYC versus high dose iv CYC) followed by maintenance therapy with azathioprine [AZA]), should serve as a model for the successful running of early phase clinical trials for severe and disabling rare diseases of childhood. The ultimate aim of these trials is to provide evidence-based information about the clinical utility of drugs in the management of rare paediatric conditions.

Study Type

Interventional

Phase

  • 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

  • Italy
      • Genoa, Italy, 16148
        • Istituto Giannina Gaslini

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

1 year to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Newly diagnosed children with untreated and biopsy proven revised WHO Class III, IV proliferative lupus nephritis and 24 hour proteinuria ≥ 500 mg/day. The kidney biopsy specimen will be read by the renal pathologists of the participating centres (light and immunofluorescence) (54). Slides of paraffin-embedded sections from all patients will be re-viewed by a blinded a renal pathologist at the PRINTO coordinating centre.

Diagnosis of JSLE according to the ACR revised classification criteria (57); Age at enrolment ≤ 18 years. Female of child-bearing potential must have a negative pregnancy test at the beginning of the trial, and then every 3 months. If sexually active, they must agree to use adequate contraception, throughout study participation, and must have no intention of conceiving during the course of the study. Post-pubertal males must have no plans to father a child during the study and agree to use adequate birth control methods if sexually active.

Ability to comply with the entire study procedures, ability to communicate meaningfully with the investigational staff, competence to give written informed consent; to be applied to the parents and/or patients, as appropriate Duly executed, written, informed consent obtained from the parents or other legal representative and/or the patient according to requirement of the local ethics committee.

Exclusion Criteria:

Treatment with the CYC, AZA or mycophenolate mofetil anytime before randomisation.

Neutrophil count <1,500 cell/mm3 and/or platelet count <50,000/mm3. History of poor compliance with previous treatment. Evidence of current use of alcohol or illicit drugs abuse. Live vaccines not allowed during the entire duration of the trial.

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: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Primary: 50% improvement in at least 2 core set variables with no more tha 1 of the remaining variables worsened by> 30%
core set variables:
physician's global assessment of disease activity on a 10 cm visual analogue scale; global disease activity measure by the mean of the European Consensus Lupus Activity parent's/patient's global assessment of overall well-being on a 10 cm VAS;
health-related quality of life assessment.

Secondary Outcome Measures

Outcome Measure
Change over time in the individual components of the JSLE
core set of variables; time to proteinuria disappearance; frequency of drop-out from
suggested steroids use; frequency of drop-out for inefficacy of treatment.

Collaborators and Investigators

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

Sponsor

Istituto Giannina Gaslini

Investigators

  • Principal Investigator: Nicolino Ruperto, MD, MPH, Istituto Giannina Gaslini-PRINTO

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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, 2006

Study Completion (Anticipated)

June 1, 2007

Study Registration Dates

First Submitted

June 12, 2006

First Submitted That Met QC Criteria

June 12, 2006

First Posted (Estimate)

June 13, 2006

Study Record Updates

Last Update Posted (Actual)

March 20, 2018

Last Update Submitted That Met QC Criteria

March 19, 2018

Last Verified

June 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IGG-PRINTO-003

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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