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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Teriflunomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed, treatment naïve ITP patients 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: Received first-line and second-line ITP-modifying therapy (any previous dose of corticosteroids or other immune-suppressive agents); Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit; Active or a history of malignancy; Positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV); Pregnancy or lactation; Pre-existing acute or chronic liver disease, or serum alanine aminotransferase (ALT) greater than 2 times the upper limit of normal (ULN); Current or recent (<4 weeks before screening) clinically serious viral, bacterial, fungal, or parasitic infection; 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; 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriflunomide plus Dexamethasone<br>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<br>* Teriflunomide 7 mg orally once daily for 24 weeks. Dose adjustments were made throughout the study based on individual platelet counts.<br>* Other names: AUBAGIO;Drug: Dexamethasone<br>* 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).<br>|
| Active Comparator: Dexamethasone<br>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<br>* 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).<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 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 | 

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