A Prospective, Randomized, Controlled Study of rhTPO in Combination With Herombopag + CsA vs Herombopag + CsA for the Treatment of Primary TD-NSAA

A Prospective, Randomized, Controlled Study of rhTPO in Combination With Herombopag + CsA vs Herombopag + CsA for the Treatment of Primary Transfusion-dependent NSAA

Aplastic anemia (AA) is a group of clinical syndromes. Treatment options are very limited. The results of a previous clinical study showed good efficacy and a high safety profile of herombopag in improving thrombocytopenia, but this result needs to be supported by more data.

In our study, patients who were willing to participate in this study and were diagnosed with transfusion-dependent non-heavy aplastic anemia were randomized to the rhTPO combined with herombopag + cyclosporine group and given rhTPO (at a dose of 1500 U by subcutaneous injection once daily for 7 d, 28 d for 3 courses) +Herombopag(10 mg/day for 3 months) + cyclosporine (3-5 mg/kg/d for 3 months). -5 mg/kg/d for at least 6 months) and herombopag + cyclosporine (10 mg/day for 3 months) + cyclosporine (3-5 mg/kg/d for at least 6 months) in the herombopag+ cyclosporine group to observe the efficacy and safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Drug Effect; Aplastic Anemia
• Intervention / Treatment: Drug: Herombopag + CsA; Drug: rhTPO combined with Herombopag + CsA

Detailed Description

Aplastic anemia (AA) is a group of clinical syndromes caused by a significant decrease in bone marrow hematopoietic tissue from different etiologies, resulting in hematopoietic failure. The prevalence of AA in China is 7.4 per 1 million. It peaks in the 15-25 and 60+ age groups and is more common in men than women. Treatment options are very limited. The results of a previous clinical study showed good efficacy and a high safety profile of herombopag in improving thrombocytopenia, but this result needs to be supported by more data.

In our study, patients who were willing to participate in this study and were diagnosed with transfusion-dependent non-heavy aplastic anemia were randomized to the rhTPO combined with herombopag + cyclosporine group and given rhTPO (at a dose of 1500 U by subcutaneous injection once daily for 7 d, 28 d for 3 courses) +Herombopag(10 mg/day for 3 months) + cyclosporine (3-5 mg/kg/d for 3 months). -5 mg/kg/d for at least 6 months) and Herombopag + cyclosporine (10 mg/day for 3 months) + cyclosporine (3-5 mg/kg/d for at least 6 months) in the herombopag+ cyclosporine group to observe the efficacy and safety.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bing Han, Doctor; Phone Number: +8601069151235; Email: hanbing_li@sina.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age ≥18 years old.
2. Clearly diagnosed untreated NSAA.
3. At least one of the following conditions was met at the time of enrollment: hemoglobin <90 g/L. Platelet <30×109/L, neutrophils <1.0×109/L.
4. Baseline liver and kidney function (ALT, AST, Cr) was less than 2 times the normal value.
5. No active infection; Not pregnant or breastfeeding.
6. Agree to sign the consent form.
7. The Eastern Cancer Collaboration Group (ECOG) score was 0-2.

Exclusion Criteria:

1. pancytopenia caused by other causes, such as myelodysplastic syndrome (MDS).
2. There is cytogenetic evidence of clonal hematologic bone marrow diseases (MDS, AML).
3. PNH clone ≥50%.
4. Had received hematopoietic stem cell transplantation (HSCT) before enrollment.
5. Immunosuppressive therapy such as ATG or cyclosporine use for more than 2 weeks.
6. Infection or bleeding that is not controlled by standard treatment.
7. Allergic to recombinant TPO or Hitrepopar.
8. Active HIV, HCV or HBV infection or cirrhosis or portal hypertension.
9. Any concomitant malignancy or local basal cell carcinoma of the skin within 5 years.
10. Previous history of thromboembolic events, heart attack or stroke (including antiphospholipid antibody syndrome) and current use of anticoagulants.
11. Women who are pregnant or nursing (lactation).
12. Have participated in other clinical trials within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Herombopag + CsA; Herombopag 10mg/ day, adjust the dose according to the blood image, the course of treatment is at least 3 months, CsA: 3-5 mg/kg/d, adjust the valley concentration 100-200ng/ml, at least 6 months, effective patients continue to use for 1 year, and then gradually reduce the dose.	Drug: Herombopag + CsA; Herombopag（10mg/d）+CsA(3-5 mg/kg/d, adjust the grain concentration 100-200ng/ml); Other Names: control
Experimental: rhTPO combined with Herombopag + CsA; Administer rhTPO (15000U, subcutaneously once daily for 7 days, once a month for 3 months),Herombopag 10mg/day, adjust dose according to blood picture for at least 3 months, CsA: 3-5 mg/kg/d, adjust trough concentration 100-200ng/ml for at least 6 months, continue for 1 year if effective, then gradually reduce dose	Drug: rhTPO combined with Herombopag + CsA; rhTPO (15000U, subcutaneous injection, once a day for 7 days, once a month for 3 months)，Herombopag（10mg/d）+CsA(3-5 mg/kg/d, adjust the grain concentration 100-200ng/ml); Other Names: experimental

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at 3 Months	After 3 months of treatment, ORR was calculated by measuring platelets, hemoglobin, neutrophils, and transfusion independence	Week 14
ORR at 6 Months	After 6 months of treatment, ORR was calculated by measuring platelets, hemoglobin, neutrophils, and transfusion independence	Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 months of drug safety	Assessing the incidence and severity of adverse events; All adverse events that occur or worsen within 3 months of treatment will be reported	Week 14
6 months of drug safety	Assessing the incidence and severity of adverse events; All adverse events that occur or worsen within 6 months of treatment will be reported	Week 26

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: August 16, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

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

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: always
• 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