Study of Sirolimus in IgG4-related Disease

NCT ID: NCT05746689

Last Updated: 2023-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-01

Study Completion Date

2028-12-31

Brief Summary

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gG4-related disease (IgG4-RD) is a newly recognized systemic autoimmune disease that can involve the pan-creatobiliary tract, retroperitoneum/aorta, head and neck region, and salivary glands, et al. Glucocorticoids are the first-line agents for the treatment of IgG4-RD, however, in order to maintain long-term disease stability and avoid disease relapse, glucocorticoids maintenance therapy should last for a long period, which may induce various glucocorticoid-associated adverse reactions. Sirolimus plays dual roles in inhibiting lymphocyte activation and fibroblast proliferation. It is inferred from its mechanism that sirolimus is a good potential treatment option for IgG4-RD. Therefore, we conducted this single-arm clinical trial on patients with IgG4-RD to determine the efficacy and safety of sirolimus.

Detailed Description

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IgG4-related disease (IgG4-RD) is a newly recognized systemic autoimmune disease that can involve the pan- creatobiliary tract, retroperitoneum/aorta, head and neck region, and salivary glands, et al. IgG4-RD is characterized by elevated serum IgG4 levels, tumefactive lesions with a dense lymphoplasmacytic infiltration rich in IgG4 positive plasma cells and storiform fibrosis of related organs.

Glucocorticoids are the first-line agents for the treatment of IgG4-RD, however, in order to maintain long-term disease stability and avoid disease relapse, glucocorticoids maintenance therapy should last for a long period, which may induce various glucocorticoid-associated adverse reactions. For some mild IgG4-RD patients without internal organ damage, long-term glucocorticoids therapy may have a low benefit/risk ratio. Further, a substantial proportion of patients cannot tolerate glucocorticoids.

Sirolimus, also known as rapamycin, is a macrolide compound that inhibits its mechanistic target (mTOR), which regulates cell growth and metabolism in response to environmental cues. mTOR is also essential in driving abnormal lineage specification within the immune system in various rheumatic diseases. We discovered that mTOR was highly activated in IgG4RD tissues, and its inhibitor sirolimus appeared as a good treatment candidate.

Conditions

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IgG4-related Disease

Keywords

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IgG4-related disease sirolimus mTOR

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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glucocorticoid and sirolimus combination therapy

Prednisone acetate 0.8mg/Kg/d (maximum dose 60mg/d), reduced by 5mg every 14 days, reduced by 2.5mg every 2 weeks after 30mg/d until discontinuation. At the same time, treatment for prevention or control of osteoporosis was given.

Sirolimus: 2mg/day for the first three days and 1mg/day thereafter. The plasma drug concentration was monitored at 14 days, 12 weeks, and 48 weeks of medication to maintain a plasma drug concentration of 4-15 ug/L.

Group Type EXPERIMENTAL

Sirolimus

Intervention Type DRUG

Sirolimus The efficacy is evaluated at 12 weeks, and treatment will be adjusted according to the control of disease and adverse effects.For experimental group, if a patient is assessed as treatment failure (TS), the patient should be withdrawn from the study and receive rescue treatment. Whereas, a patient would be transferred to the control group if he/ she cann't stand the side effects of sirolimus but not serious adverse event (SAE).

Interventions

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Sirolimus

Sirolimus The efficacy is evaluated at 12 weeks, and treatment will be adjusted according to the control of disease and adverse effects.For experimental group, if a patient is assessed as treatment failure (TS), the patient should be withdrawn from the study and receive rescue treatment. Whereas, a patient would be transferred to the control group if he/ she cann't stand the side effects of sirolimus but not serious adverse event (SAE).

Intervention Type DRUG

Other Intervention Names

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Prednisone

Eligibility Criteria

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Inclusion Criteria

1. Patients diagnosed with IgG4-RD according to the 2011 Comprehensive Diagnostic Criteria for IgG4-RD;
2. Status classified as active disease based on an IgG4-RD Responder Index (RI) ≥2 at screening.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University International Hospital

OTHER

Sponsor Role lead

Responsible Party

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Yu Ying Wang

Principal Investigato

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yuying Wang

Role: PRINCIPAL_INVESTIGATOR

Peking University International Hospital

Central Contacts

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Yuying WANG, Master

Role: CONTACT

Phone: 8615210976309

Email: [email protected]

Hui Gao, Doctor

Role: CONTACT

Phone: 8613811833264

Email: [email protected]

Other Identifiers

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Sirolimus for IgG4-RD

Identifier Type: -

Identifier Source: org_study_id