The Combination of Teriflunomide and Danazol for Steroid-resistant/Relapse Immune Thrombocytopenia

A Multicenter, Open-label, Randomized, Controlled, Phase 2 Trial Comparing the Efficacy and Safety of Teriflunomide Plus Danazol in Patients With Steroid-resistant/Relapse ITP

To compare the efficacy and safety of teriflunomide plus danazol versus danazol in patients with steroid-resistant/relapse ITP

Study Overview

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

Detailed Description

This is a prospective, multicenter, randomized, controlled trial of 124 adult patients with steroid-resistant/relapse ITP in China. Patients were randomized to receive either experimental teriflunomide plus danazol or active comparator danazol monotherapy. Treatment was discontinued if very severe or life-threatening adverse events developed or at the patient's request.

• Study Type: Interventional
• Enrollment (Estimated): 124
• 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
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking University Insititute of Hematology, Peking University People's Hospital
      • Contact: Xiao-hui Zhang, MD; Phone Number: +8613522338836; Email: zhangxh@bjmu.edu.cn
      • Contact: Li-Ping Yang, MD; Phone Number: +8618519172033; Email: lpyangvip@163.com

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 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;
3. Patients with a platelet count <30,000/μL or a platelet count <50,000/μL with bleeding manifestations at the enrollment;
4. Willing and able to sign written informed consent.

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. Pre-existing acute or chronic liver disease, or serum alanine aminotransferase (ALT) greater than two times the upper limit of normal (ULN);
4. Pregnancy or lactation;
5. Current or recent (< 4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection;
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. 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 danazol; Oral teriflunomide was given at a starting dose of 7 mg once daily and danazol was given at a dose of 200mg twice daily for 24 weeks. Treatment was discontinued if very severe or life-threatening adverse events developed or at the patient's request.	Drug: Teriflunomide; Starting dose of 7 mg once daily. Dose adjustments are made throughout the study based on individual platelet counts.; Other Names: AUBAGIO; Drug: Danazol; 200 mg twice daily.
Active Comparator: Danazol; Danazol was given at a dose of 200 mg twice a day for 24 weeks. Treatment was discontinued if very severe or life-threatening adverse events developed or at the patient's request.	Drug: Danazol; 200 mg twice daily.

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
Health-related quality of life (HRQoL)	ITP-PAQ was 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 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 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 5, 2023
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): July 15, 2025

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): December 20, 2023

Study Record Updates

• Last Update Posted (Actual): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Danazol; 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; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Danazol; Teriflunomide
• Other Study ID Numbers: PKU-TFITP-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