Herombopag Added to Cyclosporine in Non Severe Aplastic Anemia

The Efficacy and Safety of Herombopag Combined With Cyclosporine for Patients With Non Severe Aplastic Anemia

This is a prospective, multicenter, single-arm, phase 2 trial. The aim of this study is to evaluate the efficacy and safety of herombopag combined with cyclosporine for patients with non severe aplastic anemia (NSAA).

Study Overview

• Status: Recruiting
• Conditions: Non Severe Aplastic Anemia; Untreated
• Intervention / Treatment: Drug: Herombopag

Detailed Description

This study aims to improve the 24 weeks response rate. The sample size is calculated based on Simon's two-stage design. The first stage of the study enrolled a cohort of 15 patients. If after 24 weeks at least 9 patients achieved a response, then enrollment was expanded to a total of 43 patients. The null hypothesis was unaccepted if more than 26 of 43 patients achieved the response. Accounting for a 20% dropout rate, the estimated final sample size was 54 patients.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lele Zhang, PhD; Phone Number: 15811139278‬; Email: zhanglele@ihcams.ac.cn

Study Locations

• China
  • Hebei
    • Tangshan, Hebei, China
      • Not yet recruiting
      • Tangshan Central Hospital
      • Contact: Jun Li; Phone Number: 15030531816; Email: 769164130@qq.com
  • Henan
    • Zhoukou, Henan, China
      • Not yet recruiting
      • Zhoukou Central Hospital
      • Contact: Qian Liang, PhD; Phone Number: 15703815972; Email: lqw141230@163.com
  • Shandong
    • Tai'an, Shandong, China
      • Not yet recruiting
      • The Second Affilated Hospital of Shandong First Medical University
      • Contact: Hong Zhang; Phone Number: 18505386878; Email: tyfyzhh@163.com
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Regenerative Medicine Center
      • Contact: Lele Zhang, PhD; Phone Number: 15811139278‬; Email: zhanglele@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing and able to comply with the requirements for this study and written informed consent.
• Male or female age ≥ 18 years
• Diagnosis of untreated non severe aplastic anemia.
• Platelet counts < 50 x 10^9/L at least 2 times consecutively (time interval ≥ 1 week)

Exclusion Criteria:

• Receive immunosuppressive therapy more than 4 weeks before enrollment
• Treatment with TPO-RA within 1 week before enrollment
• Inherited bone marrow failure syndromes
• Bone marrow fibrosis grade ≥ 2
• The presence of hemolytic PNH clone
• The presence of clonal karyotypic abnormalities (del(20q), +8 and -Y are not included in this category)
• Previously treated with TPO-RA ≥ 4 weeks
• Previously received immunosuppressive therapy ≥ 12 weeks
• Ferritin > 1000 ng/ml (The increased level of Ferritin led by infection is not included in this category)
• Have an allergy to eltrombopag or any other part of this medicine.
• History of radiotherapy and chemotherapy for malignant solid tumors
• Cytopenia caused by other non-hematologic diseases, including liver cirrhosis, active rheumatic connective tissue disease, and persistence of infectious diseases, etc
• Abnormal liver function: ALT or AST > 3 ULN, or TBil > 1.5 ULN after treatment.
• Abnormal kidney function: Creatinine clearance < 30 ml/min, or serum creatinine (sCr) >1.5 ULN
• Patients with diabetic nephropathy, neuropathy, or eye disease
• Patients with poorly controlled hypertension or cardiac arrhythmia
• Patients with congestive heart failure and the NYHA grade ≥ 3 historically or currently, and LVEF < 45% within 4 weeks before enrollment
• History of arteriovenous thrombosis within 1 year before enrollment
• Participation in another clinical trial within 4 months before the start of this trial
• Pregnant or breast-feeding patients
• Patients considered to be ineligible for the study by the investigator for reasons other than the above

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: CsA + Herombopag; Herombopag combined with cyclosporine

Drug: Herombopag; Hetrombopag is a TPO receptor agonist approved in China in 2021 for idiopathic thrombocytopenic purpura (ITP) and second-line severe aplastic anemia (SAA). Indications of chemotherapy-induced thrombocytopenia (CIT), pediatric/juvenile ITP and naive severe aplastic anemia are under development. Hetrombopag was granted Orphan Drug Designation by FDA for the treatment of CIT. Cyclosporine A is a calcineurin inhibitor, which has an effect on reducing T-cell proliferation and activation, can reverse pancytopenia and alleviate transfusion requirements in NSAA.; Other Names: Cyclosporine A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Percentage of patients with hematological response. Hematological response is evaluated by hemoglobin, platelet and neutrophil count in the routine blood test.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Robust response rate	Percentage of patients with robust response, including complete response, near complete response, very good partial response(VGPR) and Meaningful partial response(mPR). These are evaluated by hemoglobin, platelet and neutrophil count in the routine blood test.	24 weeks
Proportion of patients with abnormal karyotype changes	The abnormal karyotype was examined by karyotype test	Baseline and 24 weeks
Time duration for patients achieving hematological response	Duration time was calculated from response to relapse.	A minimum of 2 years of planned follow-up
Change of the health-related quality of life	Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) is used to assess the health-related quality of life of patients. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100. Lower scores = more disability, higher scores = less disability	Baseline and 24 weeks
Incidence of the adverse event	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event.	24 weeks
Severity of the adverse event	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the severity.	24 weeks

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: Jiangsu Hengrui Pharmaceuticals Co.,Ltd

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 20, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; 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: MA-NSAA-II-001

Drug and device information, study documents

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