Clinical trial NCT05571332: Efficacy and Safety of Avatrombopag Combined With IST for the Treatment of HAAA and SAA With Abnormal Liver Function
Official title: Efficacy and Safety of Avatrombopag Combined With IST for the Treatment of HAAA and SAA With Abnormal Liver Function
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Aplastic Anemia
Keywords: Avatrombopag
aplastic anemia
abnormal liver function
hepatitis
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2022-10-07
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: CR rate at 12 weeks of treatment
timeFrame: 12 weeks of treatment
measure: ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 12 weeks of treatment
timeFrame: 12 weeks of treatment
Secondary outcomes:
measure: OR rate at 12 weeks of treatment
timeFrame: 12 weeks of treatment
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Anemia Therapeutic center
name: Wenrui Yang
role: STUDY_DIRECTOR
References:
citation: Young NS, Kaufman DW. The epidemiology of acquired aplastic anemia. Haematologica. 2008 Apr;93(4):489-92. doi: 10.3324/haematol.12855. No abstract available.
citation: 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.