Combination of Danazole With Berberine in the Treatment of ITP

A prospective, multicenter, open-label, Phase II, single arm, trial performed in 6 departments of hematology in China

Study Overview

• Status: Unknown
• Conditions: Corticosteroid-resistant or Relapsed ITP
• Intervention / Treatment: Drug: Berberine plus danazol

Detailed Description

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count and mucocutaneous bleeding. Approximately one-third of ITP patients fail to respond to first-line therapies. In addition, a certain amount of the patients relapse and require further therapy after one or more treatment strategies (e.g., thrombopoietin receptor agonists or rituximab). The optimal second-line treatment remains a challenge.Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as a nonprescription drug to treat diarrhea. Our previous data demonstrated that gut microbiota dysbiosis may contribute to the development of corticosteroid-resistant ITP. BBR may correct corticosteroid-resistance by modulating the gut microbiota structure, thus being a novel potential second-line candidate to treat ITP. Importantly, the potential clinical benefits of BBR have already been evaluated in various studies using human subjects, and it has been shown to be safe. Danazol is an attenuated androgen that has successfully been used in the treatment of ITP. Considering the side-effects of a regular dose of danazol and that BBR and danazol share disparate mechanisms in the treatment of ITP, we hypothesized that the combination of these two agents might be a promising option to maximize efficacy while minimizing adverse effects. Therefore, we aimed to evaluate the long-term efficacy and safety of berberine plus danazol in patients with corticosteroid-resistant or relapsed ITP.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University Institute of Hematology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinically confirmed immune thrombocytopenic purpura (ITP) newly diagnosed
2. Platelet count less than 30×109/L on two occasions or Platelets above 30×109/L combined with bleeding manifestation
3. Subject is ≥ 18 years and ≤80years
4. Subject has signed and dated written informed consent.
5. Fertile patients must use effective contraception during treatment and observational period
6. Negative pregnancy test

Exclusion Criteria:

1. Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL
2. Have an inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/or an aspartate aminotransaminase or alanine aminotransferase level > 3×upper limit of normal
3. Have a New York Heart Classification III or IV heart disease
4. Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures
5. Have active hepatitis B or hepatitis C infection
6. Have a HIV infection
7. Have active infection requiring antibiotic therapy within 7 days prior to study entry
8. Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug
9. Previous treatment with rituximab
10. Previous splenectomy
11. Had previous or concomitant malignant disease
12. Not willing to participate in the study.
13. Expected survival of < 2 years
14. Intolerant to murine antibodies
15. Immunosuppressive treatment within the last month
16. Connective tissue disease
17. Autoimmune hemolytic anemia
18. Patients currently involved in another clinical trial with evaluation of drug treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Berberine plus danazol; Berberine plus danazol group	Drug: Berberine plus danazol; Oral BBR (0.3g thrice daily) plus oral danazol (200 mg twice daily) for 16 weeks; Other Names: HangZhou Mingsheng of China

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Count of Participants That Achieved 6-month Sustained Response	6-month sustained response defined as platelet count of 30×10⁹/L or more and at least a doubling of baseline platelet count (partial response (PR)), or a platelet count of 100×10⁹/L or more and the absence of bleeding without rescue medication(complete response (CR))	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Count of Participants That Had Adverse Events	any adverse events/serious adverse events associated with study drugs and bleeding events	2 years
the Count of Participants That Achieved Initial Response	Initial response by day 28. Initial response includes partial response (PLT of 30×10⁹/L or more and at least a doubling of baseline platelet count) and complete response (PLT of 100×10⁹/L or more and the absence of bleeding without rescue medication).	4 weeks
DOR	duration of response (DOR)	2 years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Xiaohui Zhang, MD, Peking University of people's hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2016
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: April 8, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (Actual): April 10, 2019

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: corticosteroid-resistant or relapsed ITP; Danazole; berberine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Danazol
• Other Study ID Numbers: ZXH81470343

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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