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

Sponsor

Institute of Hematology & Blood Diseases Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05571332

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Aplastic Anemia	Drug: Avatrombopag 20 MG Oral Tablet	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

39 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 28, 2022

Anticipated Primary Completion Date :

Dec 28, 2023

Anticipated Study Completion Date :

Jun 28, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Avatrombopag+CsA+ p-ATG 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.	Drug: Avatrombopag 20 MG Oral Tablet p-ATG and CsA in combination with Avatrombopag to treat Other Names: porcine ATG Cyclosporine(CsA)

Arm

Intervention/Treatment

Experimental: Avatrombopag+CsA+ p-ATG

Drug: Avatrombopag 20 MG Oral Tablet

p-ATG and CsA in combination with Avatrombopag to treat

Other Names:

porcine ATG

Cyclosporine(CsA)

Outcome Measures

Primary Outcome Measures

CR rate at 12 weeks of treatment [12 weeks of treatment]
Percentage of the total number of patients receiving treatment who received a complete response at 12 weeks of treatment
ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 12 weeks of treatment [12 weeks of treatment]
Incidence of Treatment-Emergent AE by CTCAE

Secondary Outcome Measures

OR rate at 12 weeks of treatment [12 weeks of treatment]
Percentage of the total number of patients receiving treatment who received a response at 12 weeks of treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients with V/SAA with a definite diagnosis.
age between 18-70 years, male or female.
Subjects must complete all screening assessments as outlined in the trial protocol.
Able to swallow or administer the drug orally.
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.
Diagnosis as HAAA or abnormal liver function. ALT and AST more than 1.5 times of upper limit.
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:

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.);
Patients with uncontrolled bleeding and/or infection despite standard treatment.
Patients with previous history of hematopoietic stem cell transplantation; previous history of thrombosis.
Patients with concurrent malignancy or potential cancer on immunosuppressive therapy.
Those who are considered unsuitable for enrollment by the investigator.