Teriflunomide Plus High-dose Dexamethasone as First-line Treatment in Newly Diagnosed Primary Immune Thrombocytopenia

The Combination of Teriflunomide and High-dose Dexamethasone vs High-dose Dexamethasone Alone as First-line Treatment for Newly Diagnosed Adult Primary Immune Thrombocytopenia (ITP): A Prospective, Multicenter, Randomized Trial

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

Study Overview

• Status: Recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Teriflunomide; Drug: Dexamethasone

Detailed Description

This is a parallel-group, multicenter, randomized controlled trial of 132 adults with ITP in China. Patients were randomized to teriflunomide plus high-dose dexamethasone and high-dose dexamethasone monotherapy group. Patients who do not respond to dexamethasone may receive another cycle of high-dose dexamethasone therapy within 2 weeks. Platelet count, bleeding, and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiao-Hui Zhang, MD; Phone Number: +8613522338836; Email: zhangxh100@sina.com
• Study Contact Backup: Name: Li-Ping Yang, MD; Phone Number: +8618519172033; Email: lpyangvip@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
    • Peking University Insititute of Hematology, Peking University People's Hospital
    • Contact: Xiao-Hui Zhang, MD; Phone Number: +8613522338836; Email: zhangxh100@sina.com
    • Contact: Li-Ping Yang, MD; Phone Number: +8618519172033; Email: lpyangvip@163.com
  • 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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Newly diagnosed, treatment naïve ITP patients
2. Patients with a platelet count <30,000/μL or a platelet count <50,000/μL with bleeding manifestations at the enrollment;
3. Willing and able to sign written informed consent.

Exclusion Criteria:

1. Received first-line and second-line ITP-modifying therapy (any previous dose of corticosteroids or other immune-suppressive agents);
2. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit;
3. Active or a history of malignancy;
4. Positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV);
5. Pregnancy or lactation;
6. Pre-existing acute or chronic liver disease, or serum alanine aminotransferase (ALT) greater than 2 times the upper limit of normal (ULN);
7. Current or recent (<4 weeks before screening) clinically serious viral, bacterial, fungal, or parasitic infection;
8. 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;
9. Patients who are deemed unsuitable for the study by the investigator.

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: Teriflunomide plus Dexamethasone; Oral Teriflunomide was given at a dose of 7 mg once daily for 24 weeks and dexamethasone was given at a dose of 40mg, orally, once per day for 4 consecutive days (Days 1, 2, 3, and 4). Nonresponsive participants with platelets less than 20 x10^9/L or with active bleeding were allowed to repeat the 4-day course of dexamethasone treatment.	Drug: Teriflunomide; Teriflunomide 7 mg orally once daily for 24 weeks. Dose adjustments were made throughout the study based on individual platelet counts.; Other Names: AUBAGIO; Drug: Dexamethasone; Dexamethasone 40 mg orally once daily for four consecutive days (the 4-day course of dexamethasone was repeated in the case of lack of response by day 14).
Active Comparator: Dexamethasone; Dexamethasone was given at a dose of 40mg, orally, once per day for 4 consecutive days (Days 1, 2, 3, and 4). Participants in this treatment arm who failed to achieve a sustained response and had a platelet count of less than 20 x 10^9/L or with active bleeding were also allowed to repeat the 4-day course of dexamethasone treatment.	Drug: Dexamethasone; Dexamethasone 40 mg orally once daily for four consecutive days (the 4-day course of dexamethasone was repeated in the case of lack of response by day 14).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained response	Platelet count over 30,000/μL and at least a 2-fold increase of the baseline count in the absence of bleeding and rescue therapy for at least four of the six visits between weeks 19 and 24.	From the start of study treatment (Day 1) to the end of week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response	Complete response (CR) was defined as platelet count over 100,000/μL and absence of bleeding. Response (R) was defined as platelet count over 30,000/μL and at least a 2-fold increase of the baseline count and absence of bleeding.	From the start of study treatment (Day 1) to the end of week 24
Time to response	The time from treatment initiation to achieve a CR or a R.	From the start of study treatment (Day 1) to the end of week 24
Duration of response	The time from the achievement of a complete response or a partial response to the loss of response.	From the start of study treatment (Day 1) to the end of week 24
Initial response	The number of participants with achievement of CR or R at 4 weeks.	From the start of study treatment (Day 1) up to week 4 of treatment
Bleeding events	Clinically significant bleeding was assessed using the World Health Organization (WHO) bleeding scale.	From the start of study treatment (Day 1) to the end of week 24
Adverse events	Adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.	From the start of study treatment (Day 1) to the end of follow-up
Health-related quality of life (HRQoL)	ITP-patient assessment questionnaire (ITP-PAQ) was used to assess the HRQoL before and after treatment.	From the start of study treatment (Day 1) to the end of week 24

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: Xiao-Hui Zhang, MD, Peking University Institute of Hematology, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2023
• Primary Completion (Estimated): December 12, 2024
• Study Completion (Estimated): May 12, 2025

Study Registration Dates

• First Submitted: December 9, 2023
• First Submitted That Met QC Criteria: December 9, 2023
• First Posted (Actual): December 19, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Dexamethasone; Teriflunomide
• 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; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Teriflunomide
• Other Study ID Numbers: PKU-TFITP-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