NCT02703194

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
68

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Mar 2016

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 27, 2016

Completed
3 days until next milestone

Study Start

First participant enrolled

March 1, 2016

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 9, 2016

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2019

Completed
Last Updated

March 6, 2019

Status Verified

March 1, 2019

Enrollment Period

2.8 years

First QC Date

February 27, 2016

Last Update Submit

March 4, 2019

Conditions

Immunoglobulin G4 Related Sclerosing Disease

Keywords

IgG4-related diseaseIgG4-related sclerosing cholangitisMikulicz diseasePancreatitisRetroperitoneal fibrosisLymphadenopathy

Outcome Measures

Primary Outcomes (1)

  • Relapse rate at 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 Outcomes (6)

  • Relapse rate at 6 months.

    6 months

  • Complete response assessed by IgG4-RD Responder Index (IgG4-RD RI) 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.

    Up to 12 months

  • 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

  • +1 more secondary outcomes

Study Arms (2)

Prednisone

EXPERIMENTAL

Prednisone mono-therapy

Drug: Prednisone

Prednisone and Leflunomide

EXPERIMENTAL

Prednisone and Leflunomide combination therapy

Drug: PrednisoneDrug: Leflunomide

Interventions

PrednisoneDRUG

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.

Also known as: Prednisolone
PrednisonePrednisone and Leflunomide
LeflunomideDRUG

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).

Also known as: ARAVA®
Prednisone and Leflunomide

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age between 18 and 80 years.
  • 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
  • Histopathologic features consisting of dense lymphoplasmacytic infiltrate, fibrosis(usually storiform in character)and/or obliterative phlebitis within involved organs.
  • 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
  • Clinical examination showing characteristic diffuse/localized swelling or masses in single or multiple organs.
  • Hematological examination shows elevated serum IgG4 concentrations(135 mg/dl).
  • 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
  • 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.
  • 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.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Chinese PLA General Hospital

Beijing, 100000, China

Location

Related Publications (1)

  • 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.

    PMID: 32113839DERIVED

MeSH Terms

Conditions

Immunoglobulin G4-Related DiseaseMikulicz' DiseasePancreatitisRetroperitoneal FibrosisLymphadenopathy

Interventions

PrednisonePrednisoloneLeflunomide

Condition Hierarchy (Ancestors)

Autoimmune DiseasesImmune System DiseasesSalivary Gland DiseasesMouth DiseasesStomatognathic DiseasesPancreatic DiseasesDigestive System DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and SymptomsLymphatic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

PregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsPregnadienetriolsIsoxazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Jian Zhu

    Chinese PLA General Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Deputy Director of Rheumatology

Study Record Dates

First Submitted

February 27, 2016

First Posted

March 9, 2016

Study Start

March 1, 2016

Primary Completion

January 1, 2019

Study Completion

January 1, 2019

Last Updated

March 6, 2019

Record last verified: 2019-03

Locations

CN(1)