IgG4-related DiseaseNCT05746689
Study of Sirolimus in IgG4-related Disease
A study testing Sirolimus in people with IgG4-related Disease, run by Peking University International Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- IgG4-related Disease
- What is being tested?
- Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2023to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- 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.
Who cannot join
None listed.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Combination Therapy of Sirolimus and Glucocorticoids for the Maintenance of Remission in Patients With IgG4-related Disease
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.
Read the 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.
- Conditions
- IgG4-related Disease
- Being tested
- Sirolimus
- Keywords
- IgG4-related disease, sirolimus, mTOR
- Medical subject headings
- Immunoglobulin G4-Related Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Prednisone
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).
| Study group | Role | What they receive |
|---|---|---|
| glucocorticoid and sirolimus combination therapy | Experimental | 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. Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: through study completion, an average of 1 year
Secondary outcomes (3)
Disease response rate at 12 weeks
Disease response is defifined as an improvement of the IgG4-RD RI ≥2 compared with baseline.
Measured: 12 weeks of treatment
Remission rate at 48 weeks
Remission is defined as the achievement of an IgG4-RD RI of 0
Measured: 48 weeks of treatment
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
Measured: 48 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2023
- Study start1 Mar 2023 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for IgG4-related DiseaseStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University International Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yu Ying Wang, Peking University International Hospital
- Investigators
- Yuying Wang, Principal investigator, Peking University International Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05746689
- Sponsor's protocol ID
- Sirolimus for IgG4-RD
- Status last verified
- Feb 2023
- First submitted
- 13 Feb 2023
- Last updated
- 28 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Therapy of Sirolimus and Glucocorticoids for the Maintenance of Remission in Patients With IgG4-related Disease
- ClinicalTrials.gov ID
- NCT05746689
- Acronym / sponsor ID
- Sirolimus for IgG4-RD
- Conditions
- IgG4-related Disease
- Keywords
- IgG4-related disease, sirolimus, mTOR
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peking University International HospitalUniversity, hospital or other
- Study start
- 1 Mar 2023 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 28 Feb 2023 (actual)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| glucocorticoid and sirolimus combination therapy | Experimental | Drug: SirolimusPrednisone 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| SirolimusAlso: PrednisoneSirolimus 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). | Drug | glucocorticoid and sirolimus combination therapy |
Primary outcome
PrRelapse rate
Time frame: through study completion, an average of 1 year
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.
3 secondary outcomes
Disease response rate at 12 weeks
Time frame: 12 weeks of treatment
Remission rate at 48 weeks
Time frame: 48 weeks of treatment
Improvement of patient's global assessment (PGA)
Time frame: 48 weeks of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Individual participant dataSharing planned: No
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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.
Yuying Wang principal investigator
Peking University International Hospital
Questions about this trial
What is this clinical trial studying?
A study testing Sirolimus in people with IgG4-related Disease, run by Peking University International Hospital.
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 3 inclusion and 0 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: opening soon, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yuying WANG, Master (8615210976309, wangyuying028@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PrRelapse rate (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Feb 2023.