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

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.

Study Overview

• Status: Recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: Avatrombopag 20 MG Oral Tablet

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 Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fengkui Zhang, Dr.; Phone Number: +8602223909229; Email: zhangfenkui@ihcams.ac.cn
• Study Contact Backup: Name: Wenrui Yang, Dr.; Phone Number: +8602223909223; Email: yangwenrui@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
      • Contact: Liping Jing, Doctor; Phone Number: 8602223909223; Email: jingliping@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital
• Investigators: Study Director: Wenrui Yang, Anemia Therapeutic center

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Anticipated): December 28, 2023
• Study Completion (Anticipated): June 28, 2024

Study Registration Dates

• First Submitted: August 28, 2022
• First Submitted That Met QC Criteria: October 4, 2022
• First Posted (Actual): October 7, 2022

Study Record Updates

• Last Update Posted (Actual): October 7, 2022
• Last Update Submitted That Met QC Criteria: October 4, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: aplastic anemia; hepatitis; Avatrombopag; abnormal liver function
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Anemia; Bone Marrow Failure Disorders; Anemia, Aplastic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: IIT2021008-EC-1(2)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: You can ask for the researcher after completing the experiment
• IPD Sharing Time Frame: Follow-up and publication of the paper are planned for December 2024
• IPD Sharing Access Criteria: After the paper is written and published
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No