low-dose baricitinib plus danazol for steroid-resistant/relapse immune thrombocytopenia

Conditions: Immune Thrombocytopenia

Summary: this is a prospective, multicenter, randomized, controlled phase 2 trial to compare the efficacy and safety profiles in itp patients receiving baricitinib plus danazol to those receiving danazol alone.

this is a prospective, multicenter, randomized, controlled design of 216 adult patients with steroid-resistant/relapse itp in china. patients are randomly assigned at a 1:1 ratio to receive baricitinib plus danazol or danazol alone. patients in the combination therapy group receive oral baricitinib at a dose of 2 mg daily and oral danazol at a dose of 200 mg twice a day. those in the monotherapy group receive oral danazol at 200 mg twice daily. the treatment lasts for 6 months. 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, 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.

Eligibility criteria:
inclusion criteria: 1. primary immune thrombocytopenia (itp) confirmed by excluding other supervened causes of thrombocytopenia; 2. patients with chronic low platelet count (\<30,000/μl) for 6 months who have failed at least one treatment for chronic low platelet count; 3. patients who did not achieve a sustained response to treatment with full-dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation; 4. patients with a platelet count \<30,000/μl or a platelet count \<50,000/μl with clinically significant bleeding symptoms at the enrollment; 5. willing and able to provide written informed consent, and agreeable to the schedule of assessment. exclusion criteria: 1. secondary immune thrombocytopenia (e.g. patients with hiv, hcv, helicobacter pylori infection or patients with confirmed autoimmune disease); 2. active or a history of malignancy; 3. pregnancy or lactation; 4. current or recent (\<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection; 5. a history of symptomatic herpes zoster infection within 12 weeks prior to screening; 6. active or chronic viral infection from hepatitis b virus (hbv), hepatitis c virus (hcv), or human immunodeficiency virus (hiv); 7. 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; 8. 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; 9. myocardial infarction (mi), unstable ischemic heart disease, stroke, or new york heart association stage iv heart failure; 10. 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; 11. 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.

Keywords: immune thrombocytopenia baricitinib