The Safety and Efficiency of Sirolimus in Primary Antiphospholipid Syndrome: A Randomized Control Study

A Randomized, Multicenter, Double-blind, Placeobo-control Study of Sirolimus for Primary Antiphospholipid Syndrome Patients

This study is an Investigator initiated, randomized, multicenter, double-blind, placebo-control study. The aim of this study is to evaluate the safety and efficiency of Sirolimus for primaty antiphospholipid syndrome patients at week 24 and week 48.

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Antiphospholipid Syndrome
• Intervention / Treatment: Drug: Sirolimus; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liling Xu, Ph.D; Phone Number: +86 010 88324173; Email: xuliling1079@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Understand and sign the informed consent form
2. Male or Female
3. aged 18-70 at the time of screening visit
4. Met 2006 Sapporo classification criteria of APS or 2023 ACR/EULAR classification criteria of APS
5. With the stable combination therapy

Exclusion Criteria:

1. history of serious adverse events or contraindication to Sirolimus
2. Catastrophic APS within 90 days
3. Acute thrombosis within 30 days
4. ≥4/11 American College of Rheumatology Classification Criteria for SLE or other systemic autoimmune diseases
5. Historically positive HIV test or test positive at screening for HIV
6. currently on any suppressive therapy for a chronic infection (such as tuberculosis, hepatitis B infection, hepatitis C infection, CMV, EBV, Syphilis, etc)
7. Surgery treatment within one month
8. History of malignant neoplasm within the last 5 years
9. White blood cell counts<3×10*9/L
10. Abnormal Liver function tests: ALT or AST ≥ 1.5 times the upper limit of the normal value, and total bilirubin and blood lipids ≥ 2 times the upper limit of the normal value
11. Pregnant or pregnancy preparation or breastfeed
12. Any circumstances that may cause the subjects to be unable to complete the study or pose significant risks to the subjects

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sirolimus; Sirolimus 1.5mg po. QD	Drug: Sirolimus; Subjects will receive Sirolimus 1.5mg/d for 48 weeks in addition to their ongoing APS treatment regimen
Placebo Comparator: placeobo; Sirolimus placebo 1.5mg po. QD	Drug: Placebo; Subjects will receive Placebo 1.5mg/d for first 24 weeks and Sirolimus 1.5mg/d for next 24 weeks in addition to their ongoing APS treatment regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response(CR) rate at week 24	CR will be defined as follows: 1.No thrombosis events; 2.PLT ≥100 and with nobleeding; 3. No persistent autoimmnune haemolytic anaemia; 4. No skin ulcer; 5.No renal thrombotic microangiopathy; 5.Normal cognitive function (MoCA score ≥26）.	week 24
Partial response (PR) rate at week 24	PR will be defined as one of follows: 1.superficial thrombotic events;2. PLT ≥30 or increased at least 2 times of baseline and with no bleeding;3.haemoglobulin concentration normal or increased 20g/L compared to baseline; 4.50% improvement; 5. a serum creatinine level 15% abov baseline, RBCs per high-power field 50% above baseline with no casts, 50% improvement in the urinary prt:cr; 6. milde cognitive diysfunction (MoCA 9~25).	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response(CR) rate at week 48	CR will be defined as follows: 1.No thrombosis events; 2.PLT ≥100 and with nobleeding; 3. No persistent autoimmnune haemolytic anaemia; 4. No skin ulcer; 5.No renal thrombotic microangiopathy; 5.Normal cognitive function (MoCA score ≥26）.	week 48
Partial response (PR) rate at week 48	PR will be defined as one of follows: 1.superficial thrombotic events;2. PLT ≥30 or increased at least 2 times of baseline and with no bleeding;3.haemoglobulin concentration normal or increased 20g/L compared to baseline; 4.50% improvement; 5. a serum creatinine level 15% abov baseline, RBCs per high-power field 50% above baseline with no casts, 50% improvement in the urinary prt:cr; 6. milde cognitive diysfunction (MoCA 9~25).	week 48
Rate of Participants with adverse effects and serious adverse effects during treatment	Adverse effects include fever, rash, abnormal liver function, rate of new-onset infections and any abnormal measures after recivede study drug.	baseline to week 48

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Study Director: Zhanguo Li, Peking University Peoples Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 15, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: APS
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Disease; Syndrome; Antiphospholipid Syndrome; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 20240125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No