Leflunomide for Maintenance of Remission in IgG4 Related Disease

NCT ID: NCT02703194

Last Updated: 2019-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2019-01-31

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.

Conditions

Immunoglobulin G4 Related Sclerosing Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prednisone

Prednisone mono-therapy

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: DRUG

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.

Prednisone and Leflunomide

Prednisone and Leflunomide combination therapy

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: DRUG

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.

Leflunomide

Intervention Type: DRUG

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).

Interventions

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.

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Prednisolone; ARAVA®

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jian Zhu

Deputy Director of Rheumatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jian Zhu

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital

Locations

Chinese PLA General Hospital

Beijing, , China

Countries

China

References

Wang Y, Zhao Z, Gao D, Wang H, Liao S, Dong C, Luo G, Ji X, Li Y, Wang X, Zhao Y, Li K, Zhang J, Jin J, Zhang Y, Zhu J, Zhang J, Huang F. Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: A randomized clinical trial. Semin Arthritis Rheum. 2020 Dec;50(6):1513-1520. doi: 10.1016/j.semarthrit.2020.01.010. Epub 2020 Feb 3.

Reference Type: DERIVED

PMID: 32113839 (View on PubMed)

Other Identifiers

ChinaPLAGH-IgG4

Identifier Type: -

Identifier Source: org_study_id