Study of Sirolimus in CTD-TP in China (SSCI)

Sirolimus in Patients With Connective Tissue Disease Related Thrombocytopenia (CTD-TP): a Single-arm, Open-label Clinical Trial in China

We have designed a single-arm, open-label study of sirolimus in Chinese patients with refractory CTD-TP unresponsive to, or intolerant of, conventional medications at Peking Union Medical College Hospital (PUMCH). Patients received oral sirolimus at a starting dose of 2 mg per day for 3 days and a sequential dose of 1mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Patients were treated with sirolimus for more than 6 months. Safety outcomes and the efficacy endpoints were assessed in all patients who received at least one dose of treatment.

Study Overview

• Status: Unknown
• Conditions: Connective Tissue Diseases; Thrombocytopenia
• Intervention / Treatment: Drug: Sirolimus

Detailed Description

Connective tissue disease related thrombocytopenia (CTD-TP) is one of the common visceral complications of connective tissue diseases (CTD) with a poor response to traditional therapy. To date, some successful cases were reported in sirolimus treating refractory CTD-TP as a newly therapeutic method. However, there is still a lack of prospective clinical trials. This study aims to evaluate the efficacy of sirolimus in the treatment of refractory CTD-TP. To investigate this issue, investigators have designed a single-arm, open-label clinical trial of refractory CTD-TP patients in Peking Union Medical College Hospital (PUMCH). In this study, the researchers will enroll 20 patients who have a poor response to at least 6 months' traditional treatment. The participants will receive oral sirolimus treatment for 12 months. The primary end point is the change of platelet count in CBC. Secondary end points include the change of CTD activity, the time to disease complete remission and all-cause serious adverse events (SAE).

Research Question:

Does sirolimus improve the prognosis in patients with connective tissue disease related thrombocytopenia (CTD-TP) in Chinese patients?

Specific aims:

1. To determine the efficacy of sirolimus for the treatment of CTD-TP in Chinese patients
2. To evaluate the safety of sirolimus for the treatment of CTD-TP in Chinese patients
3. To analyze the clinical characteristics of CTD-TP in the sirolimus effective patients

Methods:

This is a prospective open-label trial in a period of 12 months. Thrombocytopenia is defined that the count of platelet is less than 100×109/L. CTDs include SLE, pSS, RA, scleroderma, RA, dermatomyositis and MCTD. The newly diagnosed CTD-TP patients who have received no steroid or IS treatment will be ruled out the trial. All the participants should fulfill one of the criteria of SLE, pSS, RA, scleroderma, RA, dermatomyositis and MCTD and suffer from refractory TP, or be diagnosed CTD-associated TP by two experimental rheumatologists. The current standard treatment for CTD-TP is glucocorticoid plus one kind of immunosuppressant. The patients who still have TP after more than 3 months' standard treatment will be included into the trial. After signing informed consent forms, participants will receive oral sirolimus at a starting dose of 2 mg per day for 3 days and a sequential dose of 1mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Baseline data will be collected at enrollment. All participants will finish their 5 follow-up assessments (1st mon, 2nd mon, 4th mon, 6th mon and 12th mon) in 12 months.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100005
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with refractory CTD-TP unresponsive to, or intolerant of, conventional medications at Peking Union Medical College Hospital.

Exclusion Criteria:

• new diagnosed CTD-IT patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group; participants who received sirolimus treatment	Drug: Sirolimus; Patients will receive oral sirolimus at a starting dose of 2 mg per day for 3 days and a sequential dose of 1mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with complete remission of platelet count	Complete remission of platelet count means the platelet count over 100X10^9/L. every participants will take CBC as their screening times.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with partial remission of platelet count	Partial remission of ITP means that the platelet count was less than 100X10^9/L, but it was more than two times higher than that before treatment.	6 months

Other Outcome Measures

Outcome Measure	Time Frame
Bleeding Events with treatment-related adverse events	6 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Chair: Xiaofeng Peng, Professor, Peking Union Medical College Hospital; Principal Investigator: Chanyuan WU, MD, Peking Union Medical College Hospital; Study Director: Mengtao LI, Professor, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Wu C, Wang Q, Xu D, Li M, Zeng X. Sirolimus for patients with connective tissue disease-related refractory thrombocytopenia: a single-arm, open-label clinical trial. Rheumatology (Oxford). 2021 Jun 18;60(6):2629-2634. doi: 10.1093/rheumatology/keaa645.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2017
• Primary Completion (Actual): December 31, 2018
• Study Completion (Anticipated): September 30, 2019

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 28, 2018

Study Record Updates

• Last Update Posted (Actual): April 17, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Sirolimus; thrombocytopenia; connective tissue disease
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Connective Tissue Diseases; Thrombocytopenia; 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: SirolimusforCTD-IP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Study of Sirolimus in CTD-IP in China

Drug and device information, study documents

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