Low-dose Baricitinib Plus Danazol for Steroid-resistant/Relapse Immune Thrombocytopenia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Low-dose Baricitinib Plus Danazol Versus Danazol for Patients With Steroid-resistant/Relapse Immune Thrombocytopenia: A Multicenter, Randomized, Open-label Phase 2 Trial

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Baricitinib 2 MG [Olumiant]
* Drug: Danazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia; Patients with chronic low platelet count (<30,000/μL) for 6 months who have failed at least one treatment for chronic low platelet count; 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; Patients with a platelet count <30,000/μL or a platelet count <50,000/μL with clinically significant bleeding symptoms at the enrollment; Willing and able to provide written informed consent, and agreeable to the schedule of assessment. Exclusion Criteria: Secondary immune thrombocytopenia (e.g. patients with HIV, HCV, Helicobacter pylori infection or patients with confirmed autoimmune disease); Active or a history of malignancy; Pregnancy or lactation; Current or recent (<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection; A history of symptomatic herpes zoster infection within 12 weeks prior to screening; Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV); 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; 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; Myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure; 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; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients are randomly assigned at a 1:1 ratio to receive baricitinib plus danazol or danazol alone. Each group requires 108 patients (considering 20% drop-off) to achieve the superiority comparison.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose baricitinib plus danazol<br>Oral baricitinib is given at a dose of 2 mg daily for 6 months. Danazol is given at a dose of 200 mg twice a day for 6 months. Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request. | Drug: Baricitinib 2 MG [Olumiant]<br>* Oral baricitinib was given at a dose of 2 mg daily for 6 months. Treatment was discontinued if very severe or life-threatening adverse events developed or at the patients' request.<br>* Other names: Olumiant;Drug: Danazol<br>* Danazol was given at a dose of 200 mg bid for 6 months<br>|
| Active Comparator: Danazol<br>Danazol is given at a dose of 200 mg twice a day for 6 months. Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request. | Drug: Danazol<br>* Danazol was given at a dose of 200 mg bid for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durable response | The maintenance of a 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) | A platelet count over 100,000/μL and absence of bleeding. | 1 month | 
| Response (R) | A platelet count over 30,000/μL and at least 2-fold increase of the baseline count and absence of bleeding. | 1 month | 
| Time to response | The time from starting treatment to time of achievement of CR or R. | 6 months | 
| Initial response | Achievement of CR or R at day 28 | 28 days | 
| Bleeding events | Clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale. | 6 months | 
| Health-related quality of life (HRQoL) | ITP-PAQ is used to assess the Health Related Quality of Life (HRQoL) before and after treatment. | 6 months | 
| Adverse events | Adverse events (AEs) are reported and graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune Thrombocytopenia, baricitinib