Immunoglobulin G4 Related Sclerosing DiseasePhase 4NCT02703194
Leflunomide for Maintenance of Remission in IgG4 Related Disease
A Phase 4 study testing Prednisone and Leflunomide in people with Immunoglobulin G4 Related Sclerosing Disease, run by Chinese PLA General Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Immunoglobulin G4 Related Sclerosing Disease
- What is being tested?
- Prednisone and Leflunomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteChina
- Study dates
- Mar 2016to Jan 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- Prednisone, Leflunomide
- Keywords
- IgG4-related disease, IgG4-related sclerosing cholangitis, Mikulicz disease, Pancreatitis, Retroperitoneal fibrosis, Lymphadenopathy
- Medical subject headings
- Immunoglobulin G4-Related Disease, Mikulicz' Disease, Pancreatitis, Retroperitoneal Fibrosis, Lymphadenopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoneDrug
Also called Prednisolone
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.
LeflunomideDrug
Also called ARAVA®
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).
| Study group | Role | What they receive |
|---|---|---|
| Prednisone | Experimental | Prednisone mono-therapy Receives: Drug: Prednisone |
| Prednisone and Leflunomide | Experimental | Prednisone and Leflunomide combination therapy Receives: Drug: Prednisone; Drug: Leflunomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (6)
Relapse rate at 6 months.
Relapse referred to the recurrence of previous clinical manifestations or abnormality of organ-specific imaging findings or serology tests after remission.
Measured: 6 months
Complete response assessed by IgG4-RD Responder Index (IgG4-RD RI) at 1, 3, 6 and 12 months.
Complete response (CR) is defined as IgG4-RD RI <3 at 1, 3, 6 and 12 months.
Measured: Up to 12 months
Partial response assessed by IgG4-RD RI at 1, 3, 6 and 12 months.
Partial response (PR) is defined as IgG4-RD RI remaining ≥3 at 1, 3, 6 and 12 months.
Measured: Up to 12 months
Serum IgG4 concentrations (mg/dL) measured by immunonephelometry at 1, 3, 6 and 12 months.
Measured: 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.
Measured: Up to 12 months
Adverse effect events
Treatment-related adverse effect, including abnormal liver function and leukopenia.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionJan 2019
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Immunoglobulin G4 Related Sclerosing DiseaseStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian Zhu, Chinese PLA General Hospital
- Investigators
- Jian Zhu, Principal investigator, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02703194
- Sponsor's protocol ID
- ChinaPLAGH-IgG4
- Status last verified
- Mar 2019
- First submitted
- 27 Feb 2016
- Last updated
- 6 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32113839
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Safety and Efficacy of Leflunomide for Maintenance of Remission in IgG4 Related Disease
- ClinicalTrials.gov ID
- NCT02703194
- Acronym / sponsor ID
- ChinaPLAGH-IgG4
- Keywords
- IgG4-related disease, IgG4-related sclerosing cholangitis, Mikulicz disease, Pancreatitis, Retroperitoneal fibrosis, Lymphadenopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 9 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prednisone | Experimental | Drug: PrednisonePrednisone mono-therapy |
| Prednisone and Leflunomide | Experimental | Drug: Prednisone, Drug: LeflunomidePrednisone and Leflunomide combination therapy |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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).
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrednisoneAlso: PrednisolonePrednisone: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. | Drug | Prednisone, Prednisone and Leflunomide |
| LeflunomideAlso: ARAVA®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). | Drug | Prednisone and Leflunomide |
Primary outcome
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.
6 secondary outcomes
Relapse rate at 6 months.
Time frame: 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
Partial response assessed by IgG4-RD RI at 1, 3, 6 and 12 months.
Time frame: 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
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
Adverse effect events
Time frame: Up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2019.
- Derived from this study: PubMed 32113839Wang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jian Zhu principal investigator
Chinese PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prednisone and Leflunomide in people with Immunoglobulin G4 Related Sclerosing Disease, run by Chinese PLA General Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relapse rate at 12 months. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02703194, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019.