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

NCT ID: NCT05571332

Last Updated: 2022-10-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-28
• Study Completion Date: 2024-06-28

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.

Conditions

Aplastic Anemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Avatrombopag 20 MG Oral Tablet

Intervention Type: DRUG

p-ATG and CsA in combination with Avatrombopag to treat

Interventions

Avatrombopag 20 MG Oral Tablet

p-ATG and CsA in combination with Avatrombopag to treat

Intervention Type: DRUG

Other Intervention Names

porcine ATG; Cyclosporine(CsA)

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wenrui Yang

Role: STUDY_DIRECTOR

Anemia Therapeutic center

Locations

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Fengkui Zhang, Dr.

Role: CONTACT

zhangfenkui@ihcams.ac.cn

+8602223909229

Wenrui Yang, Dr.

Role: CONTACT

yangwenrui@ihcams.ac.cn

+8602223909223

Facility Contacts

Fengkui Zhang, Doctor

Role: primary

fkzhang@ihcams.ac.cn

8602223909229

Liping Jing, Doctor

Role: backup

jingliping@ihcams.ac.cn

8602223909223

References

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.

Reference Type: RESULT

PMID: 18379007 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30504345 (View on PubMed)

Other Identifiers

IIT2021008-EC-1(2)

Identifier Type: -

Identifier Source: org_study_id