Low-dose Baricitinib Plus High-dose Dexamethasone for Patients With Newly Diagnosed Immune Thrombocytopenia

Low-dose Baricitinib Plus High-dose Dexamethasone as First-line Treatment for Patients With Newly Diagnosed Immune Thrombocytopenia: a Multicenter, Open-label, Randomized, Controlled, Phase 2 Trial

A randomized, open-label, multicenter, phase 2 trial to compare the efficacy and safety of baricitinib plus high-dose dexamethasone compared to high-dose dexamethasone monotherapy for the first-line treatment of adults with primary immune thrombocytopenia (ITP).

This is a parallel group, multicenter, randomized, controlled trial of patients with ITP in China. Patients were randomly assigned to receive baricitinib plus high-dose dexamethasone or high-dose dexamethasone monotherapy. Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request. The primary endpoint is durable response, defined as the maintenance of platelet count ≥30,000/μL and at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up.

Inclusion Criteria:

1. Confirmed newly-diagnosed, treatment-naive ITP;
2. A platelet count <30,000/μL, or a platelet count <50,000/μL with clinically significant bleeding symptoms (WHO bleeding scale 2 or above) at the enrollment;
3. Willing and able to sign written informed consent.

Exclusion Criteria:

1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit;
2. Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test;
3. Active or a history of malignancy;
4. Pregnancy or lactation;
5. Received first-line and second-line ITP-modifying therapy;
6. Previously received corticosteroids or immunosuppressive agents for non-ITP diseases within 6 months before enrollment;
7. A history of clinically significant adverse reactions to previous corticosteroid therapy;
8. Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia);
9. Current or recent (<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection;
10. A history of symptomatic herpes zoster infection within 12 weeks prior to screening;
11. Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV);
12. Have evidence of active tuberculosis (TB), or have previously had evidence of active TB and did not receive appropriate and documented treatment, or have had household contact with a person with active TB and did not receive appropriate and documented prophylaxis for TB;
13. Have experienced a clinically significant thrombotic event within 24 weeks of screening or are on anticoagulants and in the opinion of the investigator are not well controlled;
14. Myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure;
15. A history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data;
16. Any of the following specific abnormalities on screening laboratory tests:

1) ALT or AST >2 x ULN, or total bilirubin ≥1.5 x ULN 2) hemoglobin <9 g/dL, or total white blood cell (WBC) count <2,500/µL, or neutropenia (absolute neutrophil count <1,200/µL), or lymphopenia (lymphocyte count <750/µL) 3) eGFR <50 mL/min/1.73 m^2.