Phase II Study of Orelabrutinib in Combination With Romiplostim N01 in Patients With Primary Immune Thrombocytopenia (ITP) Who Have Received At Least One Prior Line of Therapy

Phase II Study of Orelabrutinib in Combination With Romiplostim in Patients With Primary Immune Thrombocytopenia (ITP) Who Have Received at Least One Prior Line of Therapy

To evaluate whether orelabrutinib combined with romiplostim N01 can improve the quality of remission, increase the probability of successful drug withdrawal, and prolong the time to treatment failure in patients with primary immune thrombocytopenia (ITP) who have received at least one line of prior therapy.

This is a prospective, single-arm, open-label Phase II study, enrolling adult patients with chronic primary immune thrombocytopenia (ITP) who failed first-line therapy. The study evaluates the efficacy and safety of orelabrutinib combined with romiplostim N01, focusing on the treatment regimen as follows:

• Core Treatment Phase (Weeks 1-24) Patients receive orelabrutinib 50mg orally once daily (fixed dose) and romiplostim N01 subcutaneously. Romiplostim N01 starts at 250ug/week (≈3ug/Kg) and is titrated within 1-10ug/Kg/week to maintain platelet count (PLT) at 50-200×10⁹/L. Dose adjustments: increase by 1-3ug/Kg/week if PLT <50×10⁹/L; decrease by 1-3ug/Kg/week if PLT 200-400×10⁹/L; suspend if PLT >400×10⁹/L. Patients with PLT <50×10⁹/L after 28 days of maximum-dose romiplostim N01 withdraw.
• Romiplostim N01 Tapering Phase (Weeks 25-32) Patients with PLT ≥50×10⁹/L in the last two core phase visits discontinue orelabrutinib. Romiplostim N01 is tapered: doses >3ug/Kg/week are reduced to 2-3ug/Kg/week, then dosing intervals extended (weekly→every 10 days→every 2 weeks). Patients with two consecutive PLT <30×10⁹/L withdraw.
• Follow-up Phase (Weeks 33-56) Successfully tapered patients are followed up every 4 weeks to monitor PLT and adverse events (graded per NCI-CTC AE 5.0). Relevant events are reported to the sponsor's Pharmacovigilance Department.

Inclusion Criteria:

1. Subjects voluntarily participate in this study and provide written informed consent；
2. Age 18-80 years, inclusive, regardless of gender；
3. ECOG score 0 to 2；
4. Documented diagnosis of chronic primary Immune Thrombocytopenia (ITP) with a disease duration >12 months；
5. Patients with an inadequate sustained response, relapse, intolerance, or insufficient response to first-line ITP therapy (corticosteroids and/or intravenous immunoglobulin). Prior receipt of other ITP treatments is allowed, with no limit on the number of prior lines；
6. A history of response to prior standard ITP therapy (defined as achieving a platelet count ≥50×10⁹/L)；
7. During or following the most recent ITP treatment, patients must have experienced either: treatment failure (platelet count <30×10⁹/L after treatment, or failure to double the baseline count, or occurrence of bleeding), relapse after initial response (platelet count decreased to <30×10⁹/L, or fell below twice the baseline, or bleeding symptoms recurred), treatment intolerance, or an inability to maintain response after treatment discontinuation；
8. Subjects demonstrate adequate comprehension of and are able to comply with the study protocol requirements, and are willing to complete the study according to the schedule.

Exclusion Criteria:

1. Subjects suffer from severe ITP at screening;
2. Subjects have other diseases which mention in protocol;
3. Subjects develop intracranial hemorrhage within 6 months prior to screening;
4. Active and uncontrollable infection;

6. Subjects have a history of coagulopathy other than ITP; 7. Subjects with a history of malignancies; 8. History of major organ transplantation or hematopoietic stem cell/bone marrow transplantation; 9. Subjects with a known history of hypersensitivity to the investigational drug as described in the Protocol, or any ingredients; 10. Subjects with a Medication history and surgical history which mention in protocol; 11. Subjects do not meet the criterion of the laboratory test in protocol.

Withdrawal Criteria:

1. If, after 4 consecutive weeks of Romiplostim N01 administration at the maximum dose (10 µg/kg once weekly), the platelet count remains <50×10⁹/L and the investigator judges the investigational product to be ineffective for the subject, such that continued use is not in the subject's best interest；
2. Subjects who are unable to successfully undergo treatment tapering or discontinuation；
3. Subjects who, during the treatment period, require rescue therapy based on clinical assessment；
4. Subjects who withdraw their informed consent.
5. Occurrence of pregnancy during the trial period
6. Poor subject compliance or a significant protocol violation；
7. Loss to follow-up；
8. The investigator decides that withdrawal is necessary for the subject's safety；
9. Presence of other conditions, as determined by the investigator, that may affect the study results or lead to premature termination of the study；
10. Study completion or early termination of the entire study.