Leflunomide for Maintenance of Remission in IgG4 Related Disease

March 4, 2019 updated by: Jian Zhu, Chinese PLA General Hospital

A Study of Safety and Efficacy of Leflunomide for Maintenance of Remission in IgG4 Related Disease

The study has been designed as a 12-month, open-label, randomized, controlled study comparing the use of prednisone mono-therapy and prednisone and leflunomide combination therapy in treating patients with IgG4-related disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The aim of this clinical trial is to determine the safety and efficacy of Leflunomide in treating patients with IgG4-related disease by comparing the outcomes of prednisone and leflunomide combination therapy with prednisone mono-therapy. The follow-up period will be 12 months. During the follow-up period, results of laboratory tests and image examinations, IgG4-RD RI and other parameters which can reflect treatment response as well as adverse effect events will be recorded.

Study Type

Interventional

Enrollment (Actual)

68

Phase

  • Phase 4

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

  • China
      • Beijing, China, 100000
        • Chinese PLA General Hospital

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

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age between 18 and 80 years.
  2. Diagnosis of IgG4-RD according to either Consensus statement on the pathology of IgG4-related disease (for those who have undergone biopsies) or 2011 Comprehensive diagnostic criteria for IgG4-related disease. Both of the two criteria for diagnosis are specified below.

(1)Consensus statement on the pathology of IgG4-related disease

  1. Histopathologic features consisting of dense lymphoplasmacytic infiltrate, fibrosis(usually storiform in character)and/or obliterative phlebitis within involved organs.
  2. Either an elevated IgG4+/IgG+cell ratio of >40% within the affected organs or elevated IgG4-bearing plasma cells per high-power field is necessary. The cut-off number of IgG4-bearing plasma cells per high-power field is different depending upon the types of affected organs and specimens(through surgery or needle puncture biopsy).

(2)2011 Comprehensive diagnostic criteria for IgG4-related disease

  1. Clinical examination showing characteristic diffuse/localized swelling or masses in single or multiple organs.
  2. Hematological examination shows elevated serum IgG4 concentrations(135 mg/dl).

  3. Histopathologic examination shows marked lymphocyte and plasmacyte infiltration and fibrosis or Infiltration of IgG4+ plasma cells(ratio of IgG4+/IgG+ cells > 40% and >10 IgG4+ plasma cells/HPF).

    Definite: a + b + c,Probable: a + c,Possible: a + b

  4. Excluded from malignant tumors of each organ (e.g. cancer, lymphoma) and similar diseases (e.g. Sjögren's syndrome, primary sclerosing cholangitis, Castleman's disease, secondary retroperitoneal fibrosis, Wegener's granulomatosis, sarcoidosis, Churg-Strauss syndrome) by additional histopathological examination.
  5. Even when patients cannot be diagnosed using the Comprehensive diagnostic criteria, they may be diagnosed using organ-specific diagnostic criteria for IgG4-RD, such as Diagnostic criteria for IgG4-Mikulicz's disease.

Exclusion Criteria:

  1. Subjects having received steroids or immunosuppressants in recent 3 months will be excluded.
  2. Subjects who were hypersensitive to leflunomide will be excluded.
  3. ALT and/or AST is more than two folds of the upper limit of relevant reference value at baseline.
  4. WBC is less than 3×10*9/L at baseline.
  5. Female patients who are pregnant or breastfeeding.
  6. Known significant concurrent medical disease.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prednisone
Prednisone mono-therapy
Drug: Prednisone
Prednisone:A starting dose of 0. 5-0. 8mg/(kg*d) will be given. Following four-week period, the dose will be tapered gradually to 5mg/d until the end of 12 months of follow-up period.
Other Names:
  • Prednisolone
Experimental: Prednisone and Leflunomide
Prednisone and Leflunomide combination therapy
Drug: Prednisone
Prednisone:A starting dose of 0. 5-0. 8mg/(kg*d) will be given. Following four-week period, the dose will be tapered gradually to 5mg/d until the end of 12 months of follow-up period.
Other Names:
  • Prednisolone
Drug: Leflunomide
Leflunomide:A starting dose of 20 mg/day will be given. This dose may be decreased to 10 mg/day at the discretion of the treating physician if minor adverse effects occur(e.g., liver enzyme elevations).
Other Names:
  • ARAVA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse rate at 12 months.
Time Frame: 12 months
Relapse referred to the recurrence of previous clinical manifestations or abnormality of organ-specific imaging findings or serology tests after remission.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse rate at 6 months.
Time Frame: 6 months
Relapse referred to the recurrence of previous clinical manifestations or abnormality of organ-specific imaging findings or serology tests after remission.
6 months
Complete response assessed by IgG4-RD Responder Index (IgG4-RD RI) at 1, 3, 6 and 12 months.
Time Frame: Up to 12 months
Complete response (CR) is defined as IgG4-RD RI <3 at 1, 3, 6 and 12 months.
Up to 12 months
Partial response assessed by IgG4-RD RI at 1, 3, 6 and 12 months.
Time Frame: Up to 12 months
Partial response (PR) is defined as IgG4-RD RI remaining ≥3 at 1, 3, 6 and 12 months.
Up to 12 months
Serum IgG4 concentrations (mg/dL) measured by immunonephelometry at 1, 3, 6 and 12 months.
Time Frame: Up to 12 months
Up to 12 months
Number of circulating plasmablasts (cell number/mL) assessed by flow cytometry by gating peripheral blood at 1, 3, 6 and 12 months.
Time Frame: Up to 12 months
Up to 12 months
Adverse effect events
Time Frame: Up to 12 months
Treatment-related adverse effect, including abnormal liver function and leukopenia.
Up to 12 months

Collaborators and Investigators

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

Sponsor

Chinese PLA General Hospital

Investigators

  • Principal Investigator: Jian Zhu, Chinese PLA General Hospital

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

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 (Actual)

March 1, 2016

Primary Completion (Actual)

January 1, 2019

Study Completion (Actual)

January 1, 2019

Study Registration Dates

First Submitted

February 27, 2016

First Submitted That Met QC Criteria

March 3, 2016

First Posted (Estimate)

March 9, 2016

Study Record Updates

Last Update Posted (Actual)

March 6, 2019

Last Update Submitted That Met QC Criteria

March 4, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ChinaPLAGH-IgG4

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.

Clinical Trials on Immunoglobulin G4 Related Sclerosing Disease

Clinical Trials on Prednisone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Serbia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe