Low-dose Baricitinib Plus High-dose Dexamethasone for Patients With Newly Diagnosed Immune Thrombocytopenia

Low-dose Baricitinib Plus High-dose Dexamethasone as First-line Treatment for Patients With Newly Diagnosed Immune Thrombocytopenia: a Multicenter, Open-label, Randomized, Controlled, Phase 2 Trial

A randomized, open-label, multicenter, phase 2 trial to compare the efficacy and safety of baricitinib plus high-dose dexamethasone compared to high-dose dexamethasone monotherapy for the first-line treatment of adults with primary immune thrombocytopenia (ITP).

Study Overview

• Status: Recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Baricitinib 2 MG; Drug: Dexamethasone

Detailed Description

This is a parallel group, multicenter, randomized, controlled trial of patients with ITP in China. Patients were randomly assigned to receive baricitinib plus high-dose dexamethasone or high-dose dexamethasone monotherapy. 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 and 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): 132
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaohui Zhang; Phone Number: +8613522338836; Email: zhangxh@bjmu.edu.cn
• Study Contact Backup: Name: Peng Zhao; Phone Number: +8618810323668; Email: zpeng702@163.com

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, China, 100044
    • Recruiting
    • Peking University Insititute of Hematology, Peking University People's Hospital
    • Contact: Peng Zhao, MD; Phone Number: +8618810323668; Email: zpeng702@163.com
    • Principal Investigator: Xiaohui Zhang, MD
    • Contact: Xiaohui Zhang, MD; Phone Number: +8613522338836; Email: zhangxh@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Confirmed newly-diagnosed, treatment-naive ITP;
2. A platelet count <30,000/μL, or a platelet count <50,000/μL with clinically significant bleeding symptoms (WHO bleeding scale 2 or above) at the enrollment;
3. Willing and able to sign written informed consent.

Exclusion Criteria:

1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit;
2. Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test;
3. Active or a history of malignancy;
4. Pregnancy or lactation;
5. Received first-line and second-line ITP-modifying therapy;
6. Previously received corticosteroids or immunosuppressive agents for non-ITP diseases within 6 months before enrollment;
7. A history of clinically significant adverse reactions to previous corticosteroid therapy;
8. Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia);
9. Current or recent (<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection;
10. A history of symptomatic herpes zoster infection within 12 weeks prior to screening;
11. Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV);
12. 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;
13. 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;
14. Myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure;
15. 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;
16. 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 high-dose dexamethasone; Oral baricitinib is given at a dose of 2 mg daily for 6 consecutive months. Dexamethasone is administrated at 40 mg per day for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10). Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request.	Drug: Baricitinib 2 MG; Baricitinib 2 mg q.d., p.o., for 6 consecutive months.; Other Names: Olumiant; Drug: Dexamethasone; Dexamethasone 40 mg q.d. for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10); Other Names: HD-DXM
Active Comparator: High-dose dexamethasone; Dexamethasone is administrated at 40 mg per day for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10). Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request.	Drug: Dexamethasone; Dexamethasone 40 mg q.d. for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10); Other Names: HD-DXM

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
Duration of response	Duration of response at 6-month follow up.	6 months
Early response	Achievement of CR or R at day 7	7 days
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.	From the start of study treatment (Day 1) to the end of week 26
Health-related quality of life (HRQoL)	ITP-PAQ is used to assess the Health Related Quality of Life (HRQoL) before and after treatment.	From the start of study treatment (Day 1) to the end of week 26
Adverse events	Adverse events (AEs) are reported and graded in accordance with the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.	From the start of study treatment (Day 1) to the end of week 26

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

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Baricitinib; High-dose dexamethasone
• 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; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: PKU-BAITP-03

Drug and device information, study documents

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