Combination of Danazole With Berberine in the Treatment of ITP

Phase 2

• Conditions: Corticosteroid-resistant or Relapsed ITP
• Interventions: Drug: Berberine plus danazol

• Registration Number: NCT03909763
• Lead Sponsor: Peking University People's Hospital

Brief Summary

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

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 Timeline

• Study Start: 2016-01-20
• Study First Submitted: 2019-04-08
• Study First Submitted QC: 2019-04-08
• Study First Posted: 2019-04-10
• Results First Submitted: 2020-08-03
• Status Verified: 2020-09
• Results First Submitted QC: 2020-09-04
• Last Update Submitted: 2020-09-04
• Results First Posted: 2020-09-25
• Last Update Posted: 2020-09-25
• Primary Completion: 2020-12-30
• Study Completion: 2021-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 55

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Berberine plus danazol	Berberine plus danazol	Berberine plus danazol group

Primary Outcome Measures

Name	Time	Method
The Count of Participants That Achieved 6-month Sustained Response	6 month	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))

Secondary Outcome Measures

Name	Time	Method
the Count of Participants That Had Adverse Events	2 years	any adverse events/serious adverse events associated with study drugs and bleeding events
the Count of Participants That Achieved Initial Response	4 weeks	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).
DOR	2 years	duration of response (DOR)

Trial Locations

Locations (1)

Peking University Institute of Hematology; 🇨🇳 Beijing, Beijing, China