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

• ClinicalTrials.gov Identifier: NCT05281068
• Recruitment Status: Recruiting
• First Posted: March 15, 2022
• Last Update Posted: May 2, 2022
• Sponsor: Peking University People's Hospital
• Collaborators: Beijing Hospital; China-Japan Friendship Hospital; Beijing Friendship Hospital; The First Affiliated Hospital of Zhengzhou University; First Affiliated Hospital of Chongqing Medical University; Shanxi Bethune Hospital
• Information provided by (Responsible Party): Xiao Hui Zhang, Peking University People's Hospital

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
ITP; Immune Thrombocytopenia	Drug: Iguratimod; Drug: Danazol	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Combination of Iguratimod and Danazol Versus Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia: A Randomized, Controlled, Multicenter, Open-label Trial
• Actual Study Start Date: September 1, 2021
• Estimated Primary Completion Date: September 1, 2023
• Estimated Study Completion Date: December 30, 2023

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Sustained response [ Time Frame: 6 months ]
   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.

Secondary Outcome Measures :

1. Complete remission [ Time Frame: 6 months ]
   The number of participants (responders) with platelet count>=100x10^9/L (CR) and the absence of bleeding.
2. Partial remission [ Time Frame: 6 months ]
   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.
3. Time to response [ Time Frame: 6 months ]
   Time to response was defined as the time from starting treatment to the time to achieve the response.
4. Duration of response [ Time Frame: 6 months ]
   Duration of response was measured from the achievement of response to the loss of response.
5. Incidence of treatment-emergent adverse events [ Time Frame: 6 months ]
   Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Xiao-Hui Zhang, MD; 15010638916; 1710301242@pku.edu.cn

Contact: Zhuo-Yu An, MD; 15010638916; anzhuoyu@pku.edu.cn

Locations

China

Zhuo-Yu An; Recruiting

Beijing, China, 100044

Contact: Zhuo-Yu An 15010638916 anzhuoyu@pku.edu.cn

Peking University Insititute of Hematology, Peking University People's Hospital; Recruiting

Beijing, China

Contact: Xiao-hui Zhang, Professor zhangxh100@sina.com

Sponsors and Collaborators

Peking University People's Hospital

Beijing Hospital

China-Japan Friendship Hospital

Beijing Friendship Hospital

The First Affiliated Hospital of Zhengzhou University

First Affiliated Hospital of Chongqing Medical University

Shanxi Bethune Hospital

Investigators

• Principal Investigator: Xiao-Hui Zhang, MD; Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology

More Information

• Responsible Party: Xiao Hui Zhang, Vice president of Peking University Institute of Hematology, Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT05281068
• Other Study ID Numbers: PKU-ITP030
• First Posted: March 15, 2022
• Last Update Posted: May 2, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Pathologic Processes; Blood Platelet Disorders; Hematologic Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Danazol; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs