Study of Sirolimus in IgG4-related Disease

Официальное название

Combination Therapy of Sirolimus and Glucocorticoids for the Maintenance of Remission in Patients With IgG4-related Disease

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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).

Первичные конечные точки

• PrRelapse rate [Срок оценки: through study completion, an average of 1 year]

Вторичные конечные точки (3)

• Disease response rate at 12 weeks [Срок оценки: 12 weeks of treatment]
• Remission rate at 48 weeks [Срок оценки: 48 weeks of treatment]
• Improvement of patient's global assessment (PGA) [Срок оценки: 48 weeks of treatment]

Критерии участия

Критерии включения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT05746689 · Sirolimus for IgG4-RD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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