High-dose dexamethasone plus orelabrutinib versus placebo for newly diagnosed adult ITP

A Randomized Controlled Study of High-Dose Dexamethasone Combined With Orelabrutinib Versus High-Dose Dexamethasone Combined With Placebo in Adult Patients With Newly Diagnosed Primary Immune Thrombocytopenia

This trial tests whether adding orelabrutinib to high-dose dexamethasone helps adults newly diagnosed with primary ITP raise and maintain their platelet counts compared with placebo.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 86 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Shandong University (Academic / other)
• Drugs / interventions: Orelabrutinib
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT07559331 on ClinicalTrials.gov

What this trial studies

This is a phase 3 randomized, placebo-controlled study enrolling adults with newly diagnosed primary immune thrombocytopenia (ITP) and platelet counts below 30×10^9/L. Participants receive high-dose dexamethasone plus either orelabrutinib or matching placebo and are followed for platelet response and safety outcomes. Eligible patients must be 18–80 years old, weigh at least 35 kg, have no active vital-organ bleeding, and must have shown a response to a prior 4-day course of oral dexamethasone as defined by protocol. The trial is being conducted at Qilu Hospital of Shandong University and uses randomized allocation to compare efficacy and tolerability between the two treatment arms.

Who should consider this trial

Good fit: Adults aged 18–80 with newly diagnosed, untreated primary ITP, platelet count <30×10^9/L, body weight ≥35 kg, no active vital-organ bleeding, and who responded to a 4-day course of oral dexamethasone are the ideal candidates.

Not a fit: Patients with chronic or previously treated ITP, those who did not respond to initial dexamethasone, children, patients under 35 kg, or those with active major-organ bleeding are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, adding orelabrutinib could increase the chance of achieving and sustaining higher platelet counts and reduce the need for additional therapies or bleeding complications.

How similar studies have performed: Other Bruton tyrosine kinase (BTK) inhibitors have shown promise in early-phase ITP studies, but confirmatory phase 3 evidence for orelabrutinib in newly diagnosed patients is limited.

Eligibility criteria

Inclusion Criteria:

1. Subjects must thoroughly understand the nature, significance, potential benefits, possible inconveniences, and potential risks of the trial prior to enrollment. They must understand the study procedures and voluntarily sign the informed consent form.
2. Male or female subjects aged 18-80 years (inclusive).
3. Body weight ≥35 kg at screening.
4. Adult patients with newly diagnosed, untreated primary ITP, with platelet count (PLT) \<30×10⁹/L and no active bleeding in vital organs.
5. Subjects who responded to prior treatment with oral dexamethasone 40 mg/day for 4 days, defined as meeting all three of the following criteria on any day between Day 5 and Day 7 post-treatment: ① PLT ≥30×10⁹/L; ② ≥2-fold increase from baseline; and ③ no active bleeding. Between Week 2 and Week 12, any abnormal PLT result meeting any of the following criteria must be confirmed by repeat testing at Qilu Hospital within 24-48 hours: ① PLT \<30×10⁹/L; ② \<2-fold increase from baseline; or ③ active bleeding.
6. Women of childbearing potential must use an effective method of contraception during the screening period, throughout the entire trial, and for 90 days following the last dose of study medication.

Exclusion Criteria:

1. Subjects with severe ITP at screening (e.g., life-threatening thrombocytopenia, major bleeding events, or requiring urgent treatment including intravenous immunoglobulin, high-dose glucocorticoids, or plasma exchange), whom the investigator anticipates will require rescue treatment within 2 weeks after enrollment.
2. Subjects with autoimmune systemic diseases other than ITP, unless the investigator determines that such conditions will not affect the evaluation of study outcomes.
3. Subjects who failed to respond to prior treatment with oral dexamethasone 40 mg/day for 4 days, defined as meeting any of the following criteria on any day between Day 5 and Day 7 post-treatment: ① PLT \<30×10⁹/L; ② \<2-fold increase from baseline; or ③ active bleeding.
4. History of intracranial hemorrhage within 6 months prior to screening.
5. Subjects with a history of coagulation disorders other than ITP, such as disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura.
6. Subjects with a known hypersensitivity to any component of the study drugs described in this protocol.
7. Known human immunodeficiency virus (HIV) infection, or positive serologic test results.
8. Subjects with positive tuberculosis screening test (based on interferon-gamma release assay, including T-SPOT®, etc.), or active, latent, or incompletely appropriately treated tuberculosis at screening.
9. Activated partial thromboplastin time (aPTT) ≥1.5× upper limit of normal (ULN) or international normalized ratio (INR) ≥1.5 at screening.
10. Organ dysfunction, with the following laboratory findings at screening: Absolute neutrophil count (ANC) \<1.5×10⁹/L; hemoglobin \<90 g/L; lymphocyte count \<0.8×10⁹/L. Total bilirubin \>1.2×ULN; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>ULN. Amylase or lipase \>2×ULN. Estimated glomerular filtration rate (eGFR) \<40 mL/min/1.73 m² calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Immunoglobulin IgG \<6 g/L.
11. Pregnant or lactating women.
12. Subjects unable to undergo blood collection, or with contraindications to phlebotomy.
13. Any other condition that the investigator considers unsuitable for participation in this trial.

Where this trial is running

Jinan, Shandong

• Qilu Hospital of Shandong University — Jinan, Shandong, China (Recruiting)

Study contacts

• Study coordinator: Min Hou, Professor

Conditions Primary Immune Thrombocytopenia