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Study of Sirolimus in IgG4-related Disease

Primary Purpose

IgG4-related Disease

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Sirolimus
Sponsored by
Peking University International Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for IgG4-related Disease focused on measuring IgG4-related disease, sirolimus, mTOR

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria: Patients diagnosed with IgG4-RD according to the 2011 Comprehensive Diagnostic Criteria for IgG4-RD; Status classified as active disease based on an IgG4-RD Responder Index (RI) ≥2 at screening. 1.Exclusion criteria: 2.Having used glucocorticoids (equivalent to more than 10mg per day of prednisone), immunosuppressant or biologic within 3 months prior to enrollment; 3.Having any contraindication of glucocorticoids or sirolimus, or allergy to sirolimus, or having experienced serious adverse reactions from previous use of any of the above drugs; 4.Combined with other connective disease; 5.History or evidence of a clinically unstable/uncontrolled disorder, condition or disease (including but not limited to cardiopulmonary, oncologic, renal, hepatic, metabolic, hematologic or psychiatric) other than IgG4-RD that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures or completion; 6.Active infection, including hepatitis B virus, hepatitis C virus, and tuberculosis; 7.Malignancy within 5 years; 8.Other serious complications or general conditions do not permit; 9.Pregnancy or to be pregnant, or breast feeding; 10.Unable to adhere to follow-up or the patient refuses to provide consent.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    glucocorticoid and sirolimus combination therapy

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    PrRelapse rate
    For patients who achieve disease response at 12 weeks, recurrence is defined as increases in the IgG4-RD RI ≥2 and/or the need for the reinstitution of treatment.

    Secondary Outcome Measures

    Disease response rate at 12 weeks
    Disease response is defifined as an improvement of the IgG4-RD RI ≥2 compared with baseline.
    Remission rate at 48 weeks
    Remission is defined as the achievement of an IgG4-RD RI of 0
    Improvement of patient's global assessment (PGA)
    PGA is a validated visual analogue scale that is scored by placing a vertical mark along a 100 mm horizontal line. Zero millimetre indicates no disease activity. A mark of 100 mm indicates the most active disease possible

    Full Information

    First Posted
    February 13, 2023
    Last Updated
    February 25, 2023
    Sponsor
    Peking University International Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05746689
    Brief Title
    Study of Sirolimus in IgG4-related Disease
    Official Title
    Combination Therapy of Sirolimus and Glucocorticoids for the Maintenance of Remission in Patients With IgG4-related Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 1, 2023 (Anticipated)
    Primary Completion Date
    December 31, 2026 (Anticipated)
    Study Completion Date
    December 31, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Peking University International Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    IgG4-related Disease
    Keywords
    IgG4-related disease, sirolimus, mTOR

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    glucocorticoid and sirolimus combination therapy
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Sirolimus
    Other Intervention Name(s)
    Prednisone
    Intervention Description
    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).
    Primary Outcome Measure Information:
    Title
    PrRelapse rate
    Description
    For patients who achieve disease response at 12 weeks, recurrence is defined as increases in the IgG4-RD RI ≥2 and/or the need for the reinstitution of treatment.
    Time Frame
    through study completion, an average of 1 year
    Secondary Outcome Measure Information:
    Title
    Disease response rate at 12 weeks
    Description
    Disease response is defifined as an improvement of the IgG4-RD RI ≥2 compared with baseline.
    Time Frame
    12 weeks of treatment
    Title
    Remission rate at 48 weeks
    Description
    Remission is defined as the achievement of an IgG4-RD RI of 0
    Time Frame
    48 weeks of treatment
    Title
    Improvement of patient's global assessment (PGA)
    Description
    PGA is a validated visual analogue scale that is scored by placing a vertical mark along a 100 mm horizontal line. Zero millimetre indicates no disease activity. A mark of 100 mm indicates the most active disease possible
    Time Frame
    48 weeks of treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion criteria: Patients diagnosed with IgG4-RD according to the 2011 Comprehensive Diagnostic Criteria for IgG4-RD; Status classified as active disease based on an IgG4-RD Responder Index (RI) ≥2 at screening. 1.Exclusion criteria: 2.Having used glucocorticoids (equivalent to more than 10mg per day of prednisone), immunosuppressant or biologic within 3 months prior to enrollment; 3.Having any contraindication of glucocorticoids or sirolimus, or allergy to sirolimus, or having experienced serious adverse reactions from previous use of any of the above drugs; 4.Combined with other connective disease; 5.History or evidence of a clinically unstable/uncontrolled disorder, condition or disease (including but not limited to cardiopulmonary, oncologic, renal, hepatic, metabolic, hematologic or psychiatric) other than IgG4-RD that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures or completion; 6.Active infection, including hepatitis B virus, hepatitis C virus, and tuberculosis; 7.Malignancy within 5 years; 8.Other serious complications or general conditions do not permit; 9.Pregnancy or to be pregnant, or breast feeding; 10.Unable to adhere to follow-up or the patient refuses to provide consent.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yuying WANG, Master
    Phone
    8615210976309
    Email
    wangyuying028@126.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hui Gao, Doctor
    Phone
    8613811833264
    Email
    gh841017@126.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Yuying Wang
    Organizational Affiliation
    Peking University International Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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