Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia

Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia: a Prospective Single Arm Study

This is a prospective one arm study to explore the efficacy and safety of Hetrombopag in non-severe aplastic anemia. Patients meeting the inclusion and exclusion criteria would be recruited. Treatment of Hetrombopag would be started with 5mg/day. The dosage would be increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L. The maximum dosage is 15mg/day. All patients would receive treatment for at least 6 months except that the platelet <20×10e9/L at the dosage of 15mg/day for 4 weeks or the platelet ≥200×10e9/L at the dosage of 5mg/week for 2 weeks. The hematological response rate and safety will be recorded and compared at D15, 1month, 1.5month, 2month, 3month, 4month, 5month, 6month, 8month, 10month and 1year.

Study Overview

• Status: Not yet recruiting
• Conditions: Drug Effect; Aplastic Anemia
• Intervention / Treatment: Drug: Hetrombopag

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Bing Han, Docter; Phone Number: +8613601059938; Email: hanbing_li@sina.com

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients diagnosed to be non-severe aplastic anemia
2. Patients with platelet count < 30×109/L and have at least one of the followings: ①absolute neutrophil count < 1.5×109/L, ②platelet count < 50×109/L, ③ hemoglobin level < 100g/L
3. Patients have no response or relapsed following at least one treatment course in a period time of > 6 months of immunosuppression containing CsA or CsA+anti-thymocyte globulin (ATG);
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
5. Patients able to understand and comply with protocol requirements and instructions and have signed and dated informed consent.

Exclusion Criteria:

1. Congenital aplastic anemia;
2. Presence of chromosomal aberration;
3. Evidence of a clonal hematologic bone marrow disorder (MDS, AML) on cytogenetics;
4. Presence with PNH clone ≥50%;
5. Patients received HSCT before;
6. Uncontrolled infection or bleeding with standard treatment;
7. Allergic to Hetrombopag or accessories;
8. HIV, HCV or HBV active infection or liver cirrhosis or portal hypertension;
9. Patient with QTcF (Fridericia's QT correction formula) at screening <450 msec, or<480 msec with bundle branch block, as determined via the mean of a triplicate ECG and assessed at site, unstable angina pectoris, uncontrolled hypertension(>180/100mmHg)，pulmonary artery hypertension;
10. Have any concomitant malignancies within 5 years expect for local basal cell carcinoma of the skin;
11. Past history of thromboembolic event, heart attack or stroke (including anti-phospholipid antibody syndrome) and current use of anticoagulants;
12. Pregnant or nursing (lactating) woman;
13. Have attended other clinical trials within 3 months;

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: treatment group; Hetrombopag would be started with 5mg/day. The dosage would be increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L. The maximum dosage is 15mg/day.	Drug: Hetrombopag; Hetrombopag starting at 5mg/day and increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at 6 Months	Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at 6 months	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of side effects at 12 months	percentage of side effects would be recorded during the study and be calculated according to CTCAE 5.0 at 12 months	12 months
ORR at 3 Months	ORR will be calculated after 3 months of treatment by measuring platelet, reticulocyte, neutrophil and transfusion independence.	3 month
Volume of Platelet Transfusions	Volume of Platelet Transfusions every month	12 months
Percentage of patients with clonal evolution at 12 months	Percentage of patients with clonal evolution would be evaluated by bone marrow biopsy at 12 months follow up.	12 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Director: Bing Han, Master, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, Hou M, Yao Y, Liu L, Wang Y, Wu D, Zhang L, Zheng C, Shen X, Hu Q, Liu J, Jin J, Luo J, Zeng Y, Gao S, Zhang X, Zhou X, Shi Q, Xia R, Xie X, Jiang Z, Gao L, Bai Y, Li Y, Xiong J, Li R, Zou J, Niu T, Yang R, Hu Y. A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia. J Hematol Oncol. 2021 Feb 25;14(1):37. doi: 10.1186/s13045-021-01047-9.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 19, 2021
• First Submitted That Met QC Criteria: August 19, 2021
• First Posted (Actual): August 24, 2021

Study Record Updates

• Last Update Posted (Actual): August 24, 2021
• Last Update Submitted That Met QC Criteria: August 19, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic
• Other Study ID Numbers: HBP-NSAA-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: individual participant data would be accepted upon request
• IPD Sharing Time Frame: 10 years
• IPD Sharing Access Criteria: email request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; 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