The Combination of Iguratimod and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia

The Combination of Iguratimod and Danazol Versus Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia: A Randomized, Controlled, Multicenter, Open-label Trial

Randomized, open-label, multicenter study to compare the efficacy and safety of combination of iguratimod and danazol versus danazol for the treatment of adults with steroid-resistant/ relapse immune thrombocytopenia (ITP).

Study Overview

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

Detailed Description

The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 100 adults with steroid-resistant/ relapse ITP in China. Patients were randomized to Iguratimod plus danazol and danazol monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Recruiting
    • Zhuo-Yu An
  • Beijing, China
    • Recruiting
    • Peking University Insititute of Hematology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia;
• Platelet count of less than 30×109/L at enrollment;
• 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;
• 18 years older;

Exclusion Criteria:

• Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus)
• Congestive heart failure
• Severe arrhythmia
• Nursing or pregnant women
• Aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the normal threshold criteria
• Creatinine or serum bilirubin levels each 1•5 times or more than the normal range
• Active or previous malignancy
• Unable to do blood routine test for the sake of time, distance, economic issues or other reasons.

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: Iguratimod and Danazol; Iguratimod is given at a dose of 25 mg bid. Danazol is given at 200mg bid for 12 weeks.	Drug: Iguratimod; Oral iguratimod (25 mg twice daily) for 12 weeks. Iguratimod is a new drug for the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), which was filed for marketing in Japan in 2003. It can significantly reduce the inflammatory response, not only selectively inhibit COX-2, but also inhibit the production of inflammatory cytokines, tumor necrosis factor, lymphocytes and immunoglobulins, and has an autoimmunomodulatory effect; it has a rapid onset of action, better efficacy and fewer adverse effects than existing drugs, and is effective in patients for whom other drugs are ineffective. It has been reported in the literature that in vitro iguratimod can inhibit the activity of nuclear factor-κB (NF-κB), which in turn inhibits the production of inflammatory cytokines (interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor alpha). Iguratimod also interacts directly with mouse and human B cells in vitro to inhibit the production of immunoglobulins.; Other Names: Iremod; Drug: Danazol; Oral danazol (200 mg twice daily) for 12 weeks.
Active Comparator: Danazol; Danazol is given at 200mg bid for 12 weeks.	Drug: Danazol; Oral danazol (200 mg twice daily) for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained response	The maintenance of platelet count ≥ 30 x 10^9/L, 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. Interim analysis was scheduled at 50% through recruitment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission	The number of participants (responders) with platelet count>=100x10^9/L (CR) and the absence of bleeding.	6 months
Partial remission	The number of participants (responders) with platelet count >=30x10^9/L and at least a 2-fold increase in the baseline count (PR) without the administration of any other platelet increasing therapy.	6 months
Time to response	Time to response was defined as the time from starting treatment to the time to achieve the response.	6 months
Duration of response	Duration of response was measured from the achievement of response to the loss of response.	6 months
Incidence of treatment-emergent adverse events	Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	6 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Beijing Friendship Hospital; Beijing Hospital; The First Affiliated Hospital of Zhengzhou University; China-Japan Friendship Hospital; First Affiliated Hospital of Chongqing Medical University; Shanxi Bethune Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: March 6, 2022
• First Submitted That Met QC Criteria: March 6, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• 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; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Danazol
• Other Study ID Numbers: PKU-ITP030

Drug and device information, study documents

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