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

Immune Thrombocytopenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05852847
• Other study ID #: PKU-BAITP-01
• Status: Recruiting
• Phase: Phase 2
• Start date: May 16, 2023
• Est. completion date: May 2025

Study information

• Verified date: June 2023
• Source: Peking University People's Hospital
• Contact: Xiaohui Zhang, MD
• Phone: +8610-8832-4672
• Email: Zhangxh[@]bjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 216
• Est. completion date: May 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

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.
• Danazol
Danazol was given at a dose of 200 mg bid for 6 months

Locations

Country	Name	City	State
China	Beijing Friendship Hospital	Beijing
China	Beijing Hospital	Beijing
China	Beijing Luhe Hospital	Beijing
China	Beijing Tsinghua Changgeng Hospital	Beijing
China	China-Japan Friendship Hospital	Beijing
China	Chinese PLA General Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Peking University Insititute of Hematology, Peking University People's Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing
China	The Sixth Medical Center of PLA General Hospital	Beijing

Sponsors (10)

Lead Sponsor	Collaborator
Peking University People's Hospital	Beijing Friendship Hospital, Beijing Hospital, Beijing Luhe Hospital, Beijing Tsinghua Changgeng Hospital, China-Japan Friendship Hospital, Chinese PLA General Hospital, Navy General Hospital, Beijing, Peking University First Hospital, Peking University Third Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Complete response (CR)	A platelet count over 100,000/µL and absence of bleeding.	1 month
Secondary	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
Secondary	Time to response	The time from starting treatment to time of achievement of CR or R.	6 months
Secondary	Initial response	Achievement of CR or R at day 28	28 days
Secondary	Bleeding events	Clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.	6 months
Secondary	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
Secondary	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