Sirolimus Monotherapy in the Treatment of Antiphospholipid Antibody Related Thrombocytopenia

Official title

Sirolimus Monotherapy in the Treatment of Antiphospholipid Antibody Related Thrombocytopenia: a Multicenter Randomized, Double Blind, Placebo Controlled, Clinical Trial

Overview

The goal of this clinical trial is to evaluate the efficacy and safety of sirolimus in patients with anti-phospholipid antibody-associated thrombocytopenia. In the 6-month randomized, double-blind, placebo-controlled phase, participants will receive either sirolimus 1 mg once daily or matching placebo. Participants will be followed at 2 weeks, 1 month, 3 months, and 6 months after enrollment. Participants who do not achieve the primary endpoint at 6 months may enter a 3-month open-label extension and receive sirolimus 1.5 mg once daily, with follow-up through month 9. The main question is whether sirolimus improves the overall response rate at 6 months compared with placebo. Primary outcome: \- Overall response rate at 6 months Secondary outcomes: * Overall response rate at 1 month and 3 months * Complete response rate at 6 months * Partial response rate at 6 months * Change in anti-phospholipid antibody titers at 6 months * Change in oral glucocorticoid dosage at 6 months Exploratory outcomes: * Proportion and reasons for early discontinuation during the double-blind phase * Among participants who do not achieve the primary endpoint at 6 months and enter the open-label extension, overall response rate, complete response rate, partial response rate, and safety outcomes after 3 months of open-label treatment

Detailed description

Complete response: the platelet count is more than or equal to 100×10\^9/L Partial response: If the platelet count is less than 100×10\^9/L, it should be more than 2 times of the baseline count Overall response: both complete and partial response

Interventions

• Drug Sirolimus
  Sirolimus 1 mg (two pills) once daily during the 6-month double-blind phase; sirolimus 1.5 mg once daily during the optional 3-month open-label extension for eligible participants.
• Drug Placebo
  Matching placebo two pills once daily during the 6-month double-blind phase; sirolimus 1.5 mg once daily during the optional 3-month open-label extension for eligible participants.

Primary outcome measures

• Percentage of participants with overall response at Month 6 [Time frame: Month 6]

Secondary outcome measures (6)

• Percentage of participants with overall response at Month 1 [Time frame: Month 1]
• Percentage of participants with overall response at Month 3 [Time frame: Month 3]
• Percentage of participants with complete response at Month 6 [Time frame: Month 6]
• Percentage of participants with partial response at Month 6 [Time frame: Month 6]
• Change from baseline in Global Antiphospholipid Syndrome Score (GAPSS) at Month 6 [Time frame: Baseline and Month 6]
• Change from baseline in oral glucocorticoid dose at Month 6 [Time frame: Baseline and Month 6]

Eligibility criteria

Inclusion criteria

• persistent positive of antiphospholipid antibody (either lupus anticoagulant, anti-cardiolipin antibody, or anti-b2GP1 antibody, at least two times with 12 weeks apart)
• persistent thrombocytopenia (30-100×10\^9/L, at least for 2 weeks)

Eligible concomitant treatment:

• prednisone or equivalent dose less than 10mg per day is allowed, and dose should be stable for more than 2 weeks
• hydroxychloroquine less than 400mg per day is allowed, and dose should be stable for more than 1 month
• anti-platelet and/or anti-coagulant therapy is allowed, and strength should be the stable for 1 week
• these following therapies should be discontinued for more than 5 half-lives before the enrollment, including thrombopoietin or thrombopoietin receptor antagonist, intravenous immunoglobulin, immunosuppressants, B cell inhibitors (Belimumab or Talitacicept) and B cell depletion therapy (Rituximab or Obinutuzumab).

Exclusion criteria

• fulling the criteria of other connective tissue disease other than antiphospholipid syndrome
• received oral/intravenous antibiotics within 2 weeks before the enrollment.
• new onset of thrombosis within 4 weeks before the enrollment.
• apparent bleeding tendency.
• life or organ threatening manifestations, includes but not limit to catastrophic antiphospholipid syndrome and thrombotic microangiopathy.
• liver and renal dysfunction: ALT or AST more than three times of upper limit of normal range; eGFR<40mL/min/1.73m\^2
• hematocytopenia: WBC<3.0×10\^9/L, Hb<100g/L.
• uncontrollable hyperlipidemia: low density lipoprotein cholesterol>3.1 mmol/L, triglycerides>2.3 mmol/L after lipid lowering therapy.
• current active infection
• women in pregnancy and postpartum period

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 10 centers

• Xiangya Hospital of Central South University — Changsha
• Qilu Hospital of Shandong University — Jinan
• West China Hospital, Sichuan University — Chengdu
• People's Hospital of Xinjiang Uygur Autonomous Region — Ürümqi
• The 1st Affiliated Hospital of Wenzhou Medical University — Wenzhou
• Beijing Chao-Yang Hospital — Beijing
• Peking University First Hospital — Beijing
• Peking University Third Hospital — Beijing
• … and 2 more centers

Identifiers

NCT: NCT06722586 · SMART_V3.0 · 2024HQ06

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗