MedPath

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

Phase 2
Recruiting
Conditions
Immune Thrombocytopenia
Interventions
Registration Number
NCT05852847
Lead Sponsor
Peking University People's Hospital
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
216
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low-dose baricitinib plus danazolBaricitinib 2 MG [Olumiant]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.
Low-dose baricitinib plus danazolDanazolOral 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.
DanazolDanazolDanazol 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.
Primary Outcome Measures
NameTimeMethod
Durable response6 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
NameTimeMethod
Adverse events6 months

Adverse events (AEs) are reported and graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Time to response6 months

The time from starting treatment to time of achievement of CR or R.

Initial response28 days

Achievement of CR or R at day 28

Bleeding events6 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.

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.

Trial Locations

Locations (10)

The Sixth Medical Center of PLA General Hospital

🇨🇳

Beijing, China

Peking University Insititute of Hematology, Peking University People's Hospital

🇨🇳

Beijing, Beijing, China

Beijing Friendship Hospital

🇨🇳

Beijing, China

Beijing Hospital

🇨🇳

Beijing, China

China-Japan Friendship Hospital

🇨🇳

Beijing, China

Chinese PLA General Hospital

🇨🇳

Beijing, China

Beijing Luhe Hospital

🇨🇳

Beijing, China

Beijing Tsinghua Changgeng Hospital

🇨🇳

Beijing, China

Peking University Third Hospital

🇨🇳

Beijing, China

Peking University First Hospital

🇨🇳

Beijing, China

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