Clinical trial NCT02703194: Leflunomide for Maintenance of Remission in IgG4 Related Disease
Official title: A Study of Safety and Efficacy of Leflunomide for Maintenance of Remission in IgG4 Related Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Immunoglobulin G4 Related Sclerosing Disease
Keywords: IgG4-related disease
IgG4-related sclerosing cholangitis
Mikulicz disease
Pancreatitis
Retroperitoneal fibrosis
Lymphadenopathy
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2016-03-09
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Relapse rate at 12 months.
timeFrame: 12 months
Secondary outcomes:
measure: Relapse rate at 6 months.
timeFrame: 6 months
measure: Complete response assessed by IgG4-RD Responder Index (IgG4-RD RI) at 1, 3, 6 and 12 months.
timeFrame: Up to 12 months
measure: Partial response assessed by IgG4-RD RI at 1, 3, 6 and 12 months.
timeFrame: Up to 12 months
measure: Serum IgG4 concentrations (mg/dL) measured by immunonephelometry at 1, 3, 6 and 12 months.
timeFrame: Up to 12 months
measure: Number of circulating plasmablasts (cell number/mL) assessed by flow cytometry by gating peripheral blood at 1, 3, 6 and 12 months.
timeFrame: Up to 12 months
measure: Adverse effect events
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
Study officials:
affiliation: Chinese PLA General Hospital
name: Jian Zhu
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.