Low-dose Baricitinib Plus Danazol for Steroid-resistant/Relapse Immune Thrombocytopenia
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Low-dose baricitinib plus danazol 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]
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.
Other Names:
Drug: Danazol
Danazol was given at a dose of 200 mg bid for 6 months
|
| Active Comparator: Danazol 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
Danazol was given at a dose of 200 mg bid for 6 months
|
Outcome Measures
Primary Outcome Measures
- Durable response [6 months]
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.
Secondary Outcome Measures
- Complete response (CR) [1 month]
A platelet count over 100,000/μL and absence of bleeding.
- Response (R) [1 month]
A platelet count over 30,000/μL and at least 2-fold increase of the baseline count and absence of bleeding.
- Time to response [6 months]
The time from starting treatment to time of achievement of CR or R.
- Initial response [28 days]
Achievement of CR or R at day 28
- Bleeding events [6 months]
Clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.
- Health-related quality of life (HRQoL) [6 months]
ITP-PAQ is used to assess the Health Related Quality of Life (HRQoL) before and after treatment.
- Adverse events [6 months]
Adverse events (AEs) are reported and graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia;
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Patients with chronic low platelet count (<30,000/μL) for 6 months who have failed at least one treatment for chronic low platelet count;
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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;
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Patients with a platelet count <30,000/μL or a platelet count <50,000/μL with clinically significant bleeding symptoms at the enrollment;
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Willing and able to provide written informed consent, and agreeable to the schedule of assessment.
Exclusion Criteria:
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Secondary immune thrombocytopenia (e.g. patients with HIV, HCV, Helicobacter pylori infection or patients with confirmed autoimmune disease);
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Active or a history of malignancy;
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Pregnancy or lactation;
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Current or recent (<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection;
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A history of symptomatic herpes zoster infection within 12 weeks prior to screening;
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Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV);
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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;
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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;
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Myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure;
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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;
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Any of the following specific abnormalities on screening laboratory tests:
- 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University Insititute of Hematology, Peking University People's Hospital | Beijing | Beijing | China | 100010 |
| 2 | Beijing Friendship Hospital | Beijing | China | ||
| 3 | Beijing Hospital | Beijing | China | ||
| 4 | Beijing Luhe Hospital | Beijing | China | ||
| 5 | Beijing Tsinghua Changgeng Hospital | Beijing | China | ||
| 6 | China-Japan Friendship Hospital | Beijing | China | ||
| 7 | Chinese PLA General Hospital | Beijing | China | ||
| 8 | Peking University First Hospital | Beijing | China | ||
| 9 | Peking University Third Hospital | Beijing | China | ||
| 10 | The Sixth Medical Center of PLA General Hospital | Beijing | China |
Sponsors and Collaborators
- Peking University People's Hospital
- Beijing Luhe Hospital
- Chinese PLA General Hospital
- Navy General Hospital, Beijing
- Beijing Hospital
- Beijing Friendship Hospital
- Peking University First Hospital
- Peking University Third Hospital
- China-Japan Friendship Hospital
- Beijing Tsinghua Changgeng Hospital
Investigators
- Principal Investigator: Xiaohui Zhang, MD, Peking University Institute of Hematology, Peking University People's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PKU-BAITP-01