Sirolimus Monotherapy in the Treatment of Antiphospholipid Antibody Related Thrombocytopenia (SMART)

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

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

Study Overview

• Status: Recruiting
• Conditions: Thrombocytopaenia; Antiphospholipid (aPL)-Positive
• Intervention / Treatment: Drug: Sirolimus; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lanlan Ji; Phone Number: +86-010-83575130; Email: thigh0829@163.com

Study Locations

• China
  • Beijing, China, 100034
    • Recruiting
    • Peking University First Hospital
    • Contact: Zhuoli Zhang; Phone Number: +86-010-83575130; Email: zhuoli.zhang@126.com
  • Beijing, China
    • Recruiting
    • Beijing Shijitan Hospital
    • Contact: Yuhua Wang; Phone Number: +86-010-63925588; Email: wangyh@bjsjth.cn
  • Beijing, China, 100020
    • Recruiting
    • Beijing Chao-Yang Hospital
    • Contact: Juan Meng; Phone Number: +86-010-85231777; Email: mserena@163.com
  • Beijing, China, 100083
    • Recruiting
    • Peking University Third Hospital
    • Contact: Rong Mu; Phone Number: +86-010-82264567; Email: murongster@163.com
  • Shanghai, China, 200001
    • Recruiting
    • Shanghai Renji Hospital
    • Contact: Ting Li; Phone Number: +86-021-5388 2125; Email: leeting007@163.com
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Xiangya Hospital of Central South University
      • Contact: Hui Luo; Phone Number: +86-0731-89753999; Email: luohui@csu.edu.cn
  • Shangdong
    • Jinan, Shangdong, China, 250012
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Qiang Shu; Phone Number: +86-531-8216-9114; Email: shuqiang@sdu.edu.cn
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Qibing Xie; Phone Number: +86-028-85422114; Email: xieqibing1971@163.com
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830001
      • Recruiting
      • People's Hospital of Xinjiang Uygur Autonomous Region
      • Contact: Lijun Wu; Phone Number: +86-991-856-5302; Email: wwlj330@126.com
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325015
      • Recruiting
      • The 1st Affiliated Hospital of Wenzhou Medical University
      • Contact: Li Sun; Phone Number: +86-0577-55578037; Email: grassandsun@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Participants receive sirolimus 1 mg (two pills) once daily for 6 months during the randomized, double-blind phase. Participants who do not achieve the primary endpoint at Month 6 may enter a 3-month open-label extension and receive sirolimus 1.5 mg once daily.	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.; Other Names: Rapamycin; mTOR inhibitor
Placebo Comparator: Control; Participants receive matching placebo (two pills) once daily for 6 months during the randomized, double-blind phase. Participants who do not achieve the primary endpoint at Month 6 may enter a 3-month open-label extension and receive sirolimus 1.5 mg once daily.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with overall response at Month 6	Overall response is defined as achieving either complete response or partial response. Complete response is defined as platelet count >=100 x 10^9/L. Partial response is defined as platelet count <100 x 10^9/L with at least a 2-fold increase from baseline. Participants with missing Month 6 assessment or meeting prespecified treatment failure criteria will be counted as non-responders.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with overall response at Month 1	Overall response is defined as achieving either complete response or partial response. Complete response is defined as platelet count >=100 x 10^9/L. Partial response is defined as platelet count <100 x 10^9/L with at least a 2-fold increase from baseline. Participants with missing Month 1 assessment or meeting prespecified treatment failure criteria will be counted as non-responders.	Month 1
Percentage of participants with overall response at Month 3	Overall response is defined as achieving either complete response or partial response. Complete response is defined as platelet count >=100 x 10^9/L. Partial response is defined as platelet count <100 x 10^9/L with at least a 2-fold increase from baseline. Participants with missing Month 3 assessment or meeting prespecified treatment failure criteria will be counted as non-responders.	Month 3
Percentage of participants with complete response at Month 6	Complete response is defined as platelet count >=100 x 10^9/L.	Month 6
Percentage of participants with partial response at Month 6	Partial response is defined as platelet count <100 x 10^9/L with at least a 2-fold increase from baseline.	Month 6
Change from baseline in Global Antiphospholipid Syndrome Score (GAPSS) at Month 6	GAPSS will be calculated at baseline and Month 6 according to the prespecified scoring algorithm based on antiphospholipid antibody profile and cardiovascular risk factors. The outcome will be reported as the change in GAPSS from baseline to Month 6, calculated as Month 6 GAPSS minus baseline GAPSS. A negative value indicates a decrease in GAPSS.	Baseline and Month 6
Change from baseline in oral glucocorticoid dose at Month 6	Oral glucocorticoid dose will be converted to prednisone-equivalent dose and summarized as the change from baseline to Month 6.	Baseline and Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of open-label extension participants with overall response at Month 9	Overall response is defined as achieving either complete response or partial response. Complete response is defined as platelet count >=100 x 10^9/L. Partial response is defined as platelet count <100 x 10^9/L with at least a 2-fold increase from baseline.	Month 9
Number of participants with serious adverse events during the double-blind treatment phase	Serious adverse events occurring after initiation of study treatment through the end of the 6-month double-blind treatment phase.	From first dose through Month 6

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Collaborators: North China Pharmaceutical Co.,Ltd

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: December 4, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: sirolimus; mTOR inhibitor; rapamycin; antiphospholipid; thrombocytopaenia
• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Blood Platelet Disorders; Hemic and Lymphatic Diseases; Thrombocytopenia; Organic Chemicals; Macrolides; Lactones; Sirolimus
• Other Study ID Numbers: SMART_V3.0; 2024HQ06 (Other Grant/Funding Number: Peking University First Hospital High Quality Clinical Research Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The de-identified participant-level STAR data underlying this study are not publicly available because they contain sensitive clinical information and public release is not covered by the applicable participant consent and ethics approval. Access may be requested from Zhuoli Zhang (zhuoli.zhang@126.com). Requests will be evaluated on the basis of scientific merit, participant privacy, ethical and institutional requirements, and the availability of a suitable data-use agreement.

Drug and device information, study documents

• 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