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

Peking University

Status and phase: Enrolling; Phase 2

Conditions: Immune Thrombocytopenia

Treatments: Drug: Baricitinib 2 MG [Olumiant]; Drug: Danazol

Study type: Interventional

Funder types: Other

Identifiers

NCT05852847

PKU-BAITP-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 216 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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216 participants in 2 patient groups

Low-dose baricitinib plus danazol

Experimental group

Description:

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.

Treatment:

Drug: Danazol

Drug: Baricitinib 2 MG [Olumiant]

Danazol

Active Comparator group

Description:

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.

Treatment:

Drug: Danazol