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

August 18, 2023 updated by: Bing Han, Peking Union Medical College Hospital

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

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. In a phase II/III, multicenter, open-label study exploring the efficacy and safety of romiplostim, the primary endpoint showed an overall response rate of 84% [95% CI 66-95%] at week 27. 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. Therefore, we aimed to compare the efficacy and safety of romiplostim in combination with CsA versus CsA monotherapy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

44

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18 years old.
  2. Clearly diagnosed as 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, 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall response rate (ORR)
Time Frame: 3, 6 months
Proportion of patients who achieved complete response and partial response.
3, 6 months
complete response rate (CRR)
Time Frame: 3, 6 months
Proportion of patients who achieved complete response.
3, 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
adverse event rate
Time Frame: 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.
3, 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2023

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

August 18, 2023

First Submitted That Met QC Criteria

August 18, 2023

First Posted (Actual)

August 24, 2023

Study Record Updates

Last Update Posted (Actual)

August 24, 2023

Last Update Submitted That Met QC Criteria

August 18, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Romiplostim-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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