Leflunomide for Maintenance of Remission in IgG4 Related Disease

Phase 4

Completed

• Conditions: Immunoglobulin G4 Related Sclerosing Disease
• Interventions: Drug: Prednisone; Drug: Leflunomide

• Registration Number: NCT02703194
• Lead Sponsor: Chinese PLA General Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2016-02-27
• Study Start: 2016-03
• Study First Submitted QC: 2016-03-03
• Study First Posted: 2016-03-09
• Primary Completion: 2019-01
• Study Completion: 2019-01
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-04
• Last Update Posted: 2019-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prednisone	Prednisone	Prednisone mono-therapy
Prednisone and Leflunomide	Prednisone	Prednisone and Leflunomide combination therapy
Prednisone and Leflunomide	Leflunomide	Prednisone and Leflunomide combination therapy

Primary Outcome Measures

Name	Time	Method
Relapse rate at 12 months.	12 months	Relapse referred to the recurrence of previous clinical manifestations or abnormality of organ-specific imaging findings or serology tests after remission.

Secondary Outcome Measures

Name	Time	Method
Relapse rate at 6 months.	6 months	Relapse referred to the recurrence of previous clinical manifestations or abnormality of organ-specific imaging findings or serology tests after remission.
Serum IgG4 concentrations (mg/dL) measured by immunonephelometry at 1, 3, 6 and 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.	Up to 12 months
Complete response assessed by IgG4-RD Responder Index (IgG4-RD RI) at 1, 3, 6 and 12 months.	Up to 12 months	Complete response (CR) is defined as IgG4-RD RI \<3 at 1, 3, 6 and 12 months.
Partial response assessed by IgG4-RD RI at 1, 3, 6 and 12 months.	Up to 12 months	Partial response (PR) is defined as IgG4-RD RI remaining ≥3 at 1, 3, 6 and 12 months.
Adverse effect events	Up to 12 months	Treatment-related adverse effect, including abnormal liver function and leukopenia.

Trial Locations

Locations (1)

Chinese PLA General Hospital; 🇨🇳 Beijing, China