TPO-RA Treatment on Immune Tolerance Induction of ITP Patients With Sustained Platelet Recovery After Treatment Termination

NCT ID: NCT06478537

Last Updated: 2024-06-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-20
• Study Completion Date: 2027-06-20

Brief Summary

The aim of this study was to observe whether maintaining a high level of platelet count after TPO-RA in patients with primary immune thrombocytopenia (ITP) can induce immune tolerance, develop immune balance in ITP patients, and enable patients to achieve a sustained response (SRoT) after TPO-RA discontinuation.

Detailed Description

In this study, ITP patients who has reached complete response (PLT ≥100 x 10^9/L）after thrombopoietin receptor agonist (TPO-RA) therapy do not rush to reduce the drug dose, so that a higher level of platelet count can be maintained for a period of time.

The treatment goal is to maintain the patient's platelet count at 300-600 × 10^9/L, and adjust the dosage of hetrombopag (2.5mg/d~7.5mg/d) based on the patient's platelet count. After 24-week TPO-RA treatment, all patients with a platelet count of ≥ 50 × 10^9/L after two consecutive visits will enter an 8-week reduction period. All patients who successfully discontinued the drug and maintained their platelet count at ≥30×109/L entered the efficacy and safety follow-up period.

The aim is to investigate whether this strategy could lead to the development or achievement of immune tolerance, achieving sustained response off treatment (SROT) (PLT≥50×109/L, no other ITP-specific medications, no bleeding) after TPO-RA discontinuation.

Conditions

Immune Thrombocytopenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

hetrombopag treatment

Group Type: EXPERIMENTAL

Hetrombopag Olamine

Intervention Type: DRUG

Treatment period: 24-week Hetrombopag (2.5mg/d~7.5mg/d) treatment.

• Two consecutive visits with PLT>600 × 10^9/L: daily dose reduction of 2.5mg; If the lowest dose has been used, extend the dosing interval.
• Two consecutive visits with PLT<300 × 10^9/L: increase the daily dose by 2.5mg until the maximum dose is reached.
• Two consecutive visits with PLT<50 × 10^9/L: increase the daily dose by 2.5mg until the maximum dose is reached; If PLT is still<50 × 10^9/L with7.5mg/d × 28d, the patient will be withdrawn.

Drug discontinuation period：8-week Hetrombopag (2.5mg/d~7.5mg/d) reduction. Hetrombopag reduces by 2.5mg every 2 weeks, and after reducing to the minimum dose of 2.5mg/d x 2 weeks, it is changed to 2.5mg once every other day (Qod) treatment, with a maximum reduction time of 8 weeks. If the PLT during two consecutive visits is less than 30 × 10^9/L, the patient will be withdrawn.

Aspirin

Intervention Type: DRUG

Aspirin 100mg, qd

Interventions

Hetrombopag Olamine

Treatment period: 24-week Hetrombopag (2.5mg/d~7.5mg/d) treatment.

• Two consecutive visits with PLT>600 × 10^9/L: daily dose reduction of 2.5mg; If the lowest dose has been used, extend the dosing interval.
• Two consecutive visits with PLT<300 × 10^9/L: increase the daily dose by 2.5mg until the maximum dose is reached.
• Two consecutive visits with PLT<50 × 10^9/L: increase the daily dose by 2.5mg until the maximum dose is reached; If PLT is still<50 × 10^9/L with7.5mg/d × 28d, the patient will be withdrawn.

Drug discontinuation period：8-week Hetrombopag (2.5mg/d~7.5mg/d) reduction. Hetrombopag reduces by 2.5mg every 2 weeks, and after reducing to the minimum dose of 2.5mg/d x 2 weeks, it is changed to 2.5mg once every other day (Qod) treatment, with a maximum reduction time of 8 weeks. If the PLT during two consecutive visits is less than 30 × 10^9/L, the patient will be withdrawn.

Intervention Type: DRUG

Aspirin

Aspirin 100mg, qd

Intervention Type: DRUG

Other Intervention Names

Hetrombopag

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years old, regardless of gender;

2. Patients with newly diagnosed or persistent primary ITP who have shown inadequate response or relapse following first-line corticosteroid treatment with or without IVIg;

3. Complete response (PLT > 100 × 10^9/L) achieved after hetrombopag treatment at doses of 2.5mg-7.5mg per day;

4. Volunteer to participate in clinical research and sign an informed consent form, willing to follow and capable of completing all trial procedures.

Exclusion Criteria

1. Age>50 years old;

2. Those who are contraindicated to taking aspirin;

3. Previous arterial or venous thrombosis history (including coronary atherosclerotic heart disease, ischemic stroke, deep vein thrombosis or pulmonary embolism, etc.) or clinical symptoms and medical history indicate thrombophilia;

4. Risk factors of cardiovascular diseases such as hypertension, diabetes and hyperlipidemia;

5. Heart disease occurring within the first 3 months of screening, including congestive heart failure classified as III/IV by the New York Heart Association (NHYA), arrhythmias or myocardial infarction requiring medication, or arrhythmias known to increase the risk of thrombotic events (such as atrial fibrillation), or prolonged QT interval (QTc) after subject correction (QTc>450 milliseconds, or QTc>480 milliseconds in subjects with bundle branch block)

6. Patients currently undergoing anticoagulant therapy or antiplatelet therapy;

7. Female patients receiving estrogen replacement therapy or oral contraceptives;

8. Patients with past or current malignant tumors;

9. Secondary thrombocytopenia, such as myelodysplastic syndrome, immune disorders such as systemic lupus erythematosus, early aplastic anemia, atypical aplastic anemia, antiphospholipid syndrome, thrombotic thrombocytopenic purpura, and other causes of thrombocytopenia;

10. The results of bone marrow biopsy during the screening period indicate that the bone marrow fibrosis MF is ≥ 2 (Thieleja 2005, the European expert consensus bone marrow fibrosis scoring standard), or that bone marrow biopsy suggests the presence of other primary diseases that can cause thrombocytopenia besides ITP;

11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are three times higher than the upper limit of normal values, total bilirubin is three times higher than the upper limit of normal values, and blood creatinine is 1.5 times higher than the upper limit of normal values;

12. Have a history of liver cirrhosis or portal hypertension;

13. Uncontrollable infections;

14. Hepatitis B surface antigen positive or previous history of hepatitis B, and in the past 3 months, accompanied by HBV-DNA ≥ 2000IU/ML; those with positive hepatitis C antibody, HCV-RNA positive in the past 3 months;

15. Individuals who test positive for antibodies against human immunodeficiency virus or specific antibodies against Treponema pallidum;

16. Individuals who are known to be allergic to the drug itself or its excipients;

17. Breastfeeding or pregnant women or female patients planning to conceive during the study period; 18）Other situations determined by the researcher as unsuitable for participation in this study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tienan Zhu

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tienan Zhu, M.D.

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tienan Zhu, M.D.

Role: CONTACT

zhutn@pumch.cn

01069155027

Facility Contacts

Tienan Zhu, M.D.

Role: primary

zhutn@pumch.cn

01069155027

Other Identifiers

I-24PJ1123

Identifier Type: -

Identifier Source: org_study_id