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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Teriflunomide
* Drug: Danazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia; 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; Patients with a platelet count <30,000/μL or a platelet count <50,000/μL with bleeding manifestations at the enrollment; Willing and able to sign written informed consent. Exclusion Criteria: Secondary immune thrombocytopenia (e.g. patients with HIV, HCV, Helicobacter pylori infection, or patients with confirmed autoimmune disease); Active or a history of malignancy; Pre-existing acute or chronic liver disease, or serum alanine aminotransferase (ALT) greater than two times the upper limit of normal (ULN); Pregnancy or lactation; Current or recent (< 4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection; Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV); 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; 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; Patients who are deemed unsuitable for the study by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients were randomly assigned at a 1:1 ratio to receive teriflunomide plus danazol or danazol. Each group requires 62 patients (considering a 10% drop-off).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriflunomide plus danazol<br>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<br>* Starting dose of 7 mg once daily. Dose adjustments are made throughout the study based on individual platelet counts.<br>* Other names: AUBAGIO;Drug: Danazol<br>* 200 mg twice daily.<br>|
| Active Comparator: Danazol<br>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<br>* 200 mg twice daily.<br>|

What is the study measuring?
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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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Teriflunomide, Danazol