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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Baricitinib 2 MG
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed newly-diagnosed, treatment-naive ITP; 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; Willing and able to sign written informed consent. Exclusion Criteria: Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit; 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; Active or a history of malignancy; Pregnancy or lactation; Received first-line and second-line ITP-modifying therapy; Previously received corticosteroids or immunosuppressive agents for non-ITP diseases within 6 months before enrollment; A history of clinically significant adverse reactions to previous corticosteroid therapy; Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia); 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 high-dose dexamethasone or high-dose dexamethasone alone. Each group requires 66 patients (considering 10% drop-off).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose baricitinib plus high-dose dexamethasone<br>Oral baricitinib is given at a dose of 2 mg daily for 6 consecutive months. Dexamethasone is administrated at 40 mg per day for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10). Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request. | Drug: Baricitinib 2 MG<br>* Baricitinib 2 mg q.d., p.o., for 6 consecutive months.<br>* Other names: Olumiant;Drug: Dexamethasone<br>* Dexamethasone 40 mg q.d. for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10)<br>* Other names: HD-DXM;|
| Active Comparator: High-dose dexamethasone<br>Dexamethasone is administrated at 40 mg per day for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10). Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request. | Drug: Dexamethasone<br>* Dexamethasone 40 mg q.d. for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10)<br>* Other names: HD-DXM;|

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 | 
| Duration of response | Duration of response at 6-month follow up. | 6 months | 
| Early response | Achievement of CR or R at day 7 | 7 days | 
| 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. | From the start of study treatment (Day 1) to the end of week 26 | 
| Health-related quality of life (HRQoL) | ITP-PAQ is used to assess the Health Related Quality of Life (HRQoL) before and after treatment. | From the start of study treatment (Day 1) to the end of week 26 | 
| Adverse events | Adverse events (AEs) are reported and graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. | From the start of study treatment (Day 1) to the end of week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Baricitinib, High-dose dexamethasone