Romiplostim in Combination With CsA vs. CsA in the Treatment of Newly Diagnosed NSAA

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06009497

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Non Severe Aplastic Anemia	Drug: Romiplostim Drug: Ciclosporin	Phase 4

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. Treatment options for patients with aplastic anemia are very limited. By binding to the thrombopoietin (TPO) receptor, thrombopoietin receptor agonists (TPO-RAs) can cause conformational changes in the TPO receptor, activate the JAK2/STATS pathway, and increase megakaryocyte progenitor cells proliferation and platelet production. At present, TPO-RAs including eltrombopag, lusutrombopag, romiplostim, and avatrombopag have been approved by FDA. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, 31 patients with refractory AA were enrolled. The primary endpoint for the proportion of patients who achieved any hematological (platelet, neutrophil, and red blood cell) response at week 27 was 84% [95% CI 66-95%]. At week 53, the three-line response rate was 39% (95% CI 22-58%). However, there are no prospective clinical data exploring whether romiplostim combined with ciclosporin (CsA) can further improve efficacy than ciclosporin monotherapy in newly diagnosed NSAA. Since romiplostim and CsA have good safety, if it is proved that the combination of the two drugs is superior to ciclosporin monotherapy, it can quickly improve blood patterns in NSAA, avoid the use of more expensive ATG, and provide some help to reduce the economic burden of AA patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Romiplostim in Combination With Ciclosporin Versus Ciclosporin in the Treatment of Newly Diagnosed Non-severe Aplastic Anemia

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Romiplostim+CsA Romiplostim 10 µg/kg, subcutaneous injection, once a week, for at least 3 months. Patients with platelet count ≥50×109/L can stop using, and continue to use with platelet count < 50×109/L. Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.	Drug: Romiplostim Romiplostim 10 µg/kg, subcutaneous injection, once a week. Drug: Ciclosporin Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.
Experimental: CsA Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.	Drug: Ciclosporin Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.

Arm

Intervention/Treatment

Experimental: Romiplostim+CsA

Romiplostim 10 µg/kg, subcutaneous injection, once a week, for at least 3 months. Patients with platelet count ≥50×109/L can stop using, and continue to use with platelet count < 50×109/L. Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.

Drug: Romiplostim

Romiplostim 10 µg/kg, subcutaneous injection, once a week.

Drug: Ciclosporin

Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.

Experimental: CsA

Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml. Ciclosporin should be used for at least 6 months to evaluate the efficacy. Effective patients will continue to use ciclosporin for at least 1.5 years, followed by a slow reduction.

Drug: Ciclosporin

Ciclosporin 3-5mg/kg/d, adjust the dose to keep trough ciclosporin plasma concentration 100-200ng/ml.

Outcome Measures

Primary Outcome Measures

overall response rate (ORR) [3, 6 months]
Proportion of patients who achieved complete response and partial response.
complete response rate (CRR) [3, 6 months]
Proportion of patients who achieved complete response.

Secondary Outcome Measures

adverse event rate [3, 6 months]
All adverse events that occur or worsen during treatment, as well as those that occur later but are believed by the investigator to be related to the investigational drug, will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years old.
Clearly diagnosed as untreated NSAA.
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.
Baseline liver and kidney function (ALT, AST, Cr) was less than 2 times the normal value.
No active infection; Not pregnant or breastfeeding.
Agree to sign the consent form.
The Eastern Cancer Collaboration Group (ECOG) score was 0-2.

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking union medical college hospital	Beijing		China

Sponsors and Collaborators

Peking Union Medical College Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Bing Han, Professor, Peking Union Medical College Hospital

ClinicalTrials.gov Identifier:

NCT06009497

Other Study ID Numbers:

Romiplostim-1

First Posted:

Aug 24, 2023

Last Update Posted:

Aug 24, 2023

Last Verified:

Aug 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 24, 2023