The Safety and Efficacy Study of Avatrombopag Switch in TPO-RA Refractory AA

Avatrombopag in TPO-RA Refractory Aplastic Anemia Patients Safety and Efficacy Study --Single-arm, Multicenter, Open, Phase Π Clinical Study

This study was a single-arm, multicenter, phase Π clinical study. Patients admitted to the enrollment unit center with a confirmed diagnosis of TDNSAA/VSAA/SAA, treated with IST (p/r-ATG+CSA) in combination with TPO-RA (including eltrombopta or hydtrombopta) for at least 3 months with no hematologic response at 6-month follow-up, and who were not suitable or unwilling to undergo hematopoietic stem cell transplantation (HSCT), were to another novel TPO-RA avatrombopta, 40-60 mg (weight <80 kg), in addition to maintaining the original immunosuppressive therapy ( CSA or equivalent immune potency drugs), switch to another new TPO-RA avatropa 40-60 mg (40 mg daily for weight <80 kg; 60 mg daily for weight >80 kg) orally once daily for at least 3 months and follow up for 3 months to determine the hematologic response and to assess the safety of the drug

Study Overview

• Status: Recruiting
• Conditions: Refractory Aplastic Anemia
• Intervention / Treatment: Drug: avatrombopag

Detailed Description

This study was a single-arm, multicenter, phase Π clinical study. Patients admitted to the enrollment unit center with a confirmed diagnosis of TDNSAA/VSAA/SAA, treated with IST (p/r-ATG+CSA) in combination with TPO-RA (including eltrombopta or hydtrombopta) for at least 3 months with no hematologic response at 6-month follow-up, and who were not suitable or unwilling to undergo hematopoietic stem cell transplantation (HSCT), were to another novel TPO-RA avatrombopta, 40-60 mg (weight <80 kg), in addition to maintaining the original immunosuppressive therapy ( CSA or equivalent immune potency drugs), switch to another new TPO-RA avatropa 40-60 mg (40 mg daily for weight <80 kg; 60 mg daily for weight >80 kg) orally once daily for at least 3 months and follow up for 3 months to determine the hematologic response and to assess the safety of the drug.Selection of study population Severe aplastic anemia patients with poor efficacy of IST combined with TPO-RA Patients should be judged for inclusion and exclusion criteria. Number of subjects: 35 effective cases, 39 patients should be included according to the dropout rate of 10%.

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

Contacts and Locations

• Study Contact: Name: Liping Jing, Doctor; Phone Number: 8602223909223; Email: jingliping@ihcams.ac.an

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: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of the following criteria:

1. Patients with confirmed TDNSAA/SAA/VSAA aplastic anemia who received standard IST therapy for at least 6 months, combined with Haitrombopag (15mg/d) or Eltrombopag (>50mg/d) for at least 3 Patients who have not obtained a hematological response (NR) for months and are not suitable or unwilling to undergo HSCT
2. Age > 14 years old, male or female.
3. Subjects must complete all screening assessments listed in the trial protocol.
4. ECOG score ≤ 2 points.
5. Before the start of the research procedure, the patient or guardian should fully understand the research procedure and purpose and sign the informed consent form. If the patient's signature is not conducive to the treatment of the disease, the patient's immediate family should sign the informed consent form.

Exclusion Criteria: Subjects meeting any of the following criteria were excluded from this study:

1. Patients with severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis, various bacterial and viral infections) and active bleeding that cannot be controlled after standard treatment.
2. Patients with AIDS, active viral hepatitis B, and hepatitis C RNA nucleic acid test positive.
3. Those who are pregnant or breastfeeding, have fertility but are unwilling to take effective contraceptive measures.
4. Congenital hematopoietic failure diseases (such as Fanconi anemia).
5. Patients with cytogenetic clonal changes (excluding germline mutations and acquired chromosome clones of +8, 20q- and -y).
6. Combined with malignant tumor within 3 years.
7. Combined with other systemic diseases that cannot be controlled.
8. Significant abnormalities in cardiopulmonary function.
9. Abnormal liver and kidney function: creatinine level > 1.5 times the upper limit of normal, transaminase and bilirubin level > 2 times the upper limit of normal, and those who cannot be enrolled in the group as judged by the clinician.
10. 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 in RAA; After the patients met the above-mentioned inclusion conditions and signed informed consent, they began to be included in this program. The main research objectives are to take avatrombopag conversion therapy for at least 3 months, to monitor hematological indicators, biochemical indicators and bone marrow related tests, to determine hematological responses, and to evaluate the safety of the drug. In the 6th and 12th months after treatment, comprehensive review of bone marrow and peripheral blood was performed to evaluate the recovery of hematopoiesis, determine the curative effect, evaluate adverse events, and whether there was clonal transformation. After the patients completed the main study observation, they were followed up for at least 3 months, that is, from the time the patients were enrolled, for a total of at least 6 months of follow-up.

Drug: avatrombopag; Avatrombopag, 40-60 mg (body weight < 80 kg, 40 mg per day; body weight > 80 kg, 60 mg per day) orally once daily for at least 3 months and followed up for 3 months to determine hematological response and evaluate the drug security.; Other Names: CSA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of HR in patients after switching to avatrombopag.	Percentage of the total number of patients receiving treatment who received APAG	3 months
Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading	Incidence of Treatment-Emergent AE by CTCAE	3 months
Percentage of patients with transformation	Rate of patients with transformation to PNH or MDS,AML, or other disease	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of HR in patients after switching to avatrombopag.	Percentage of the total number of patients receiving treatment who received APAG	6months
ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading	Incidence of Treatment-Emergent AE by CTCAE	6months
Percentage of patients with transformation	Rate of patients with transformation to PNH or MDS,AML, or other disease	6months
The rate of HR in patients after switching to avatrombopag.	Percentage of the total number of patients receiving treatment who received APAG	12months
ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading	Incidence of Treatment-Emergent AE by CTCAE	12months
Percentage of patients with transformation	Rate of patients with transformation to PNH or MDS,AML, or other disease	12months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital
• Collaborators: Peking University People's Hospital; Xiyuan Hospital of China Academy of Chinese Medical Sciences; The First Hospital of Hebei Medical University; First Affiliated Hospital of Harbin Medical University; Second Hospital of Shanxi Medical University
• Investigators: Study Director: Liping Jing, Doctor, Anemia Treatment Center

Publications and helpful links

General Publications

• 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.
• Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan;172(2):187-207. doi: 10.1111/bjh.13853. Epub 2015 Nov 16. No abstract available. Erratum In: Br J Haematol. 2016 Nov;175(3):546.
• Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med. 2017 Apr 20;376(16):1540-1550. doi: 10.1056/NEJMoa1613878.
• Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012 Jul 5;367(1):11-9. doi: 10.1056/NEJMoa1200931. Erratum In: N Engl J Med. 2012 Jul 19;367(3):284.
• Peng G, He G, Chang H, Gao S, Liu X, Chen T, Li P, Han B, Miao M, Ge Z, Ge X, Li F, Li Y, Wang S, Wang Y, Shen Y, Zhang T, Zou J, Zhang F. A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy. Ther Adv Hematol. 2022 Mar 30;13:20406207221085197. doi: 10.1177/20406207221085197. eCollection 2022.
• Ise M, Iizuka H, Kamoda Y, Hirao M, Kida M, Usuki K. Romiplostim is effective for eltrombopag-refractory aplastic anemia: results of a retrospective study. Int J Hematol. 2020 Dec;112(6):787-794. doi: 10.1007/s12185-020-02971-1. Epub 2020 Sep 2.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: June 11, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): August 26, 2022
• Last Update Submitted That Met QC Criteria: August 25, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Avatrombopag, TPO-RA, refractory aplastic anemia
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic
• Other Study ID Numbers: IIT2021008-EC-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We can share the plan after completing the experiment
• IPD Sharing Time Frame: Follow-up and publication of the paper are planned for December 2025
• IPD Sharing Access Criteria: After the paper is written and published
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); 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