Avatrombopag Usage in NSAA

Efficacy and Safety of Avatrombopag in Non-severe Aplastic Anemia - a Multicenter Prospective Single Arm Study

This is a multicenter, open-label, prospective one arm study to explore the efficacy and safety of Avatrombopag in non-severe aplastic anemia. Patients meeting the inclusion and exclusion criteria would be recruited. Treatment of Avatrombopag would be started with 20mg/day. The dosage would be increased by 20 mg/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 dosage could range from 20mg/week to 60mg/day. All patients would receive treatment for at least 6 months except that the platelet <20×10e9/L at the dosage of 60mg/day for 4 weeks or the platelet ≥200×10e9/L at the dosage of 20mg/week for 2 weeks. The hematological response rate and safety will be recorded and compared at every month after starting the study treatment. The patients would be followed up for at least 6 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Drug Effect; Aplastic Anemia
• Intervention / Treatment: Drug: Avatrombopag 20 MG

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

Contacts and Locations

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 have at least one of the followings: ①absolute neutrophil count < 1.5×109/L, ②platelet count < 30×109/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 Avatrombopag 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: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Avatrombopag treatment group; Avatrombopag would be started with 20mg/day. The dosage would be increased by 20 mg/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 dosage could range from 20mg/week to 60mg/day.	Drug: Avatrombopag 20 MG; Avatrombopag 20mg/week to 60mg/day, starting at 20mg/day and increased by 20 mg/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 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at 3 Months	ORR will be calculated after 3 months of treatment by measuring platelet, reticulocyte, neutrophil and transfusion independence.	3 months
Percentage of patients with clonal evolution at 6 months	Percentage of patients with clonal evolution would be evaluated by bone marrow biopsy at 6 months follow up.	6 months
percentage of side effects at 6 months	percentage of side effects would be recorded during the study and be calculated according to CTCAE 5.0 at 6 months	6 months
Total volume of Platelet Transfusions	Total volume of Platelet Transfusions	1 month
Total volume of Red Blood Cells Transfusions	Total volume of Red Blood Cells Transfusions	1 month

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2021
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): June 30, 2023

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (ACTUAL): January 28, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 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: Avatrombopag-1

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