Sirolimus Monotherapy in the Treatment of Antiphospholipid Antibody Related Thrombocytopenia

NCT06722586 | Recruiting Phase 4

• 2 other identifiers: SMART_V3.02024HQ06
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

Antiphospholipid (aPL)-Positive; Thrombocytopaenia

Keywords

antiphospholipid; thrombocytopaenia; sirolimus; rapamycin; mTOR inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Percentage of participants with overall response at Month 1

  Month 1

• Percentage of participants with overall response at Month 3

  Month 3

• Percentage of participants with complete response at Month 6

  Month 6

• Percentage of participants with partial response at Month 6

  Month 6

• Change from baseline in Global Antiphospholipid Syndrome Score (GAPSS) at Month 6

  Baseline and Month 6

Other Outcomes (2)

• Percentage of open-label extension participants with overall response at Month 9

  Month 9

• Number of participants with serious adverse events during the double-blind treatment phase

  From first dose through Month 6

Study Arms (2)

Treatment

EXPERIMENTAL

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

Control

PLACEBO COMPARATOR

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

Interventions

Sirolimus DRUG

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.

Also known as: Rapamycin, mTOR inhibitor

Treatment

Placebo DRUG

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.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University First Hospital: lead
• North China Pharmaceutical Co.,Ltd: collaborator

Study Sites (10)

Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, Shangdong, 250012, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

People's Hospital of Xinjiang Uygur Autonomous Region

Ürümqi, Xinjiang, 830001, China

RECRUITING

The 1st Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325015, China

RECRUITING

Beijing Chao-Yang Hospital

Beijing, 100020, China

RECRUITING

Peking University First Hospital

Beijing, 100034, China

RECRUITING

Peking University Third Hospital

Beijing, 100083, China

RECRUITING

Beijing Shijitan Hospital

Beijing, China

RECRUITING

Shanghai Renji Hospital

Shanghai, 200001, China

RECRUITING

MeSH Terms

Conditions

Thrombocytopenia

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Lanlan Ji

CONTACT

+86-010-83575130; thigh0829@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Director of Rheumatology and Immunology Department

Model Details: Participants are randomized 1:1 to receive sirolimus 1.0 mg or matching placebo during a 6-month double-blind, parallel-group 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.

Study Record Dates

• First Submitted: December 4, 2024
• First Posted: December 9, 2024
• Study Start: January 7, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 30, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)