Efficacy and Safety of Avatrombopag Combined With IST for the Treatment of HAAA and SAA With Abnormal Liver Function

Aplastic Anemia Clinical Trial

Official title:

Efficacy and Safety of Avatrombopag Combined With IST for the Treatment of HAAA and SAA With Abnormal Liver Function

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05571332
• Other study ID #: IIT2021008-EC-1(2)
• Status: Recruiting
• Phase: N/A
• Start date: June 28, 2022
• Est. completion date: June 28, 2024

Study information

• Verified date: August 2022
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Fengkui Zhang, Dr.
• Phone: +8602223909229
• Email: zhangfenkui[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, single-arm clinical study. The objective was to evaluate the efficacy and safety of Avatrombopag combined with IST in very/sever aplastic anemia patients with abnormal liver function or HAAA patients treated for the first time. The design was: Patients received p-ATG for 5 consecutive days (day 1-5), at a dose of 20 mg/kg/day. Cyclosporine 3 mg/kg orally in two divided doses, with cyclosporine trough concentrations maintained at 200-250 ng/ml for 3 months to achieve maximum efficacy, and Avatrombopag, which was administered in the dose of 40 mg orally once daily for a total of 12 weeks. Thirty-nine patients are expected to be enrolled in this study. Evaluation endpoint: complete response rate at 12 weeks of treatment.

Description:

This is a multicenter, single-arm clinical study to evaluate the efficacy and safety of Avatrombopag combined with IST as the first-line regimen for aplastic anemia. The patients are diagnosed as hepatitis associated with very sever/sever aplastic anemia(V/SAA) or V/SAA with abnormal liver function before treatment. Patients received p-ATG for 5 consecutive days (day 1-5), at a dose of 20 mg/kg/day. CSA is started at 3 mg/kg orally in two doses. Concentrations maintained at 200-250 ng/ml to achieve maximum efficacy and then tapered by 25 mg every 3 months; Avatrombopag: 40 mg orally once daily for a total of 12 weeks. A total of 39 patients were expected to be included.Complete response rate at 12 weeks of treatment and adverse events are the evaluation endpoint.Secondary study endpoints were: ORR at 12 , CRR and ORR at 24 weeks, survival, and clonal evolution in follow-up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 39
• Est. completion date: June 28, 2024
• Est. primary completion date: December 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. patients with V/SAA with a definite diagnosis.

2. age between 18-70 years, male or female.

3. Subjects must complete all screening assessments as outlined in the trial protocol.

4. Able to swallow or administer the drug orally.

5. No prior application of TPO receptor agonists (including Thrombopoietin, Eltrombopag, Hetrombopag, etc.) or application of TPO receptor agonists for treatment with = 5 total doses and = 7 days of TPO receptor agonist drugs such as Eltrombopag, Hetrombopag, etc.

6. Diagnosis as HAAA or abnormal liver function. ALT and AST more than 1.5 times of upper limit.

7. Informed consent must be signed prior to the start of all specific study procedures, in consideration of the patient's condition, or by a member of the patient's immediate family if the patient's signature is not conducive to the treatment of the condition.

Exclusion Criteria:

1. Known diagnosis of congenital hematopoietic failure disorders (e.g. Fanconi anemia) and other causes of allogeneic cytopenias and bone marrow hypoproliferative disorders (e.g. hemolytic PNH, hypoproliferative MDS/AML, autoantibody-mediated allogeneic cytopenias, etc.);

2. Patients with uncontrolled bleeding and/or infection despite standard treatment.

3. Patients with previous history of hematopoietic stem cell transplantation; previous history of thrombosis.

4. Patients with concurrent malignancy or potential cancer on immunosuppressive therapy.

5. Those who are considered unsuitable for enrollment by the investigator.

Related Conditions & MeSH terms

• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• Avatrombopag 20 MG Oral Tablet
p-ATG and CsA in combination with Avatrombopag to treat

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

Scheinberg P. Activity of eltrombopag in severe aplastic anemia. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):450-456. doi: 10.1182/asheducation-2018.1.450. Review. — View Citation

Young NS, Kaufman DW. The epidemiology of acquired aplastic anemia. Haematologica. 2008 Apr;93(4):489-92. doi: 10.3324/haematol.12855. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CR rate at 12 weeks of treatment	Percentage of the total number of patients receiving treatment who received a complete response at 12 weeks of treatment	12 weeks of treatment
Primary	ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 12 weeks of treatment	Incidence of Treatment-Emergent AE by CTCAE	12 weeks of treatment
Secondary	OR rate at 12 weeks of treatment	Percentage of the total number of patients receiving treatment who received a response at 12 weeks of treatment	12 weeks of treatment