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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
68

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chinese PLA General Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 27, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 9, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 6, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 4, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ChinaPLAGH-IgG4

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