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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Baricitinib 2 MG [Olumiant]; Drug: Danazol

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 Type: Interventional
• Enrollment (Estimated): 216
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Zhao, MD; Phone Number: +8618810323668; Email: zpeng702@163.com
• Study Contact Backup: Name: Xiaohui Zhang, MD; Phone Number: +8610-8832-4672; Email: Zhangxh@bjmu.edu.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Hospital
    • Contact: Hui Liu, MD; Phone Number: +861088324672; Email: fengru2019@126.com
  • Beijing, China
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Dai Hong Liu, MD; Phone Number: +861088326666; Email: 1510301227@bjmu.edu.cn
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital
    • Contact: Hong Mei Jing, MD; Phone Number: +861088324672; Email: 1510301227@bjmu.edu.cn
  • Beijing, China
    • Recruiting
    • Beijing Friendship Hospital
    • Contact: Zhao Wang, MD; Phone Number: +861088324672; Email: wangliru2019@126.com
  • Beijing, China
    • Recruiting
    • China-Japan Friendship Hospital
    • Contact: Zhen Ling Li, MD; Phone Number: +861088324672; Email: Lizhenling1994@163.com
  • Beijing, China
    • Recruiting
    • Peking University first hospital
    • Contact: Yu Jun Dong, MD; Phone Number: +861088324577; Email: 1510301227@bjmu.edu.cn
  • Beijing, China
    • Recruiting
    • Beijing luhe hospital
    • Contact: He Bing Zhou, MD; Phone Number: +861088324672; Email: zhouhebing2019@126.com
  • Beijing, China
    • Recruiting
    • Beijing Tsinghua Changgeng Hospital
    • Contact: Li Hong Li, MD; Phone Number: +861088324672; Email: 1510301227@bjmu.edu.cn
  • Beijing, China
    • Recruiting
    • The Sixth Medical Center of PLA General Hospital
    • Contact: Yi Liu, MD; Phone Number: +861088324577; Email: drliuyi@126.com
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking University Insititute of Hematology, Peking University People's Hospital
      • Contact: Xiao Hui Zhang, MD; Phone Number: +8610-8832-4672; Email: zhangxh100@sina.com
      • Contact: Peng Zhao, doctor; Phone Number: +8618810323668; Email: zpeng702@163.com
      • Principal Investigator: Xiao Hui Zhang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Olumiant; 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

What is the study measuring?

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
Time to response	The time from starting treatment to time of achievement of CR or R.	6 months
Initial response	Achievement of CR or R at day 28	28 days
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
Bleeding events	Clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.	6 months
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
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

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Peking University First Hospital; Beijing Friendship Hospital; Chinese PLA General Hospital; Peking University Third Hospital; Beijing Hospital; China-Japan Friendship Hospital; Navy General Hospital, Beijing; Beijing Luhe Hospital; Beijing Tsinghua Changgeng Hospital
• Investigators: Principal Investigator: Xiaohui Zhang, MD, Peking University Institute of Hematology, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 11, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Immune Thrombocytopenia; baricitinib
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Danazol
• Other Study ID Numbers: PKU-BAITP-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No