Efficacy of Romiplostim in Treatment of Severe Aplastic Anemia in Non-Asian Adults Previously Untreated With or Refractory to Immunosuppressive Therapy

JRCT ID: jRCT2031230178

Registered date:25/06/2023

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Severe Aplastic Anemia (SAA)
• Date of first enrollment: 31/08/2023
• Target sample size: 0
• Study type: Interventional

Intervention(s)

- Experimental: Arm 1: Previously Untreated IST
Participants with SAA/vSAA that are previously untreated with IST.
Interventions:
- Drug: Romiplostim
- Drug: Antithymocyte Globulin
- Drug: Cyclosporine A

- Experimental: Arm 2: Refractory IST
Participants with SAA/vSAA that are refractory to IST.
Intervention: Drug: Romiplostim

Outcome(s)

Primary Outcome

1. Arms 1 and 2: proportion of participants achieving any hematologic response at week 14[ Time Frame: Week 14 ]
Proportion of participants achieving any hematologic response at week 14 based on response criteria:
- Platelet response
- Erythroid response
- Red blood cell count
- Hemoglobin concentration
- Neutrophil response

Secondary Outcome

1. Arm 1: number of participants who achieve a complete response (CR) or partial response (PR) at week 14 [ Time Frame: Week 14 ]
2. Arms 1 and 2: number of participants who have a decrease in frequency of platelet and/or red blood cell (RBC) transfusions, or become platelet and/or RBC transfusion independent at week14 [ Time Frame: Week 14 ]
3. Arms 1 and 2: number of participants with serious adverse events [ Time Frame: 24 Weeks ]
4. Arms 1 and 2: number of participants with clinically significant changes in laboratory values[ Time Frame: 24 Weeks ]
5. Arms 1 and 2: change from baseline in Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) bleeding scale at week 14 [ Time Frame: Baseline and Week 14 ]
The Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto is as follows:
0: No bleeding
a. Petecjoae or mucosal or retinal bleeding that did not require red-cell transfusion
b. Melena, hematemesis, hematuria, or hemoptysis
c. Any bleeding that required red-cell transfusion
d. Retinal bleeding accompanied by visual impairment
e. Nonfatal cerebral bleeding
f. Fatal cerebral bleeding
g. Fatal noncerebral bleeding
6. Arms 1 and 2: serum romiplostim trough concentrations [ Time Frame: Prior to romiplostim administration on Weeks 1, 2, 4, 5, 9, 13, and 24 ]
7. Arms 1 and 2: maximum serum concentration (Cmax) of romiplostim [ Time Frame: Weeks 1, 2,4, 5, 9, 13, and 24 ]
8. Arms 1 and 2: area under the curve (AUC) of romiplostim [ Time Frame: Weeks 1, 2, 4, 5, 9, 13,and 24 ]
9. Arms 1 and 2: time to reach maximum concentration (tmax) of romiplostim [ Time Frame: Weeks1, 2, 4, 5, 9, 13, and 24 ]
10. Arms 1 and 2: half-life (t1/2) of romiplostim [ Time Frame: Weeks 1, 2, 4, 5, 9, 13, and 24 ]
11. Arms 1 and 2: number of participant with anti-romiplostim antibodies [ Time Frame: Prior to romiplostim administration on Weeks 1 and 13 ]
12. Arms 1 and 2: number of participants with antibodies to thrombopoietin [ Time Frame: Prior to romiplostim administration on Weeks 1 and 13 ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Age >= 18 years at time of enrollment
2. Diagnosis of SAA/vSAA confirmed by blood, bone marrow, and cytogenetic studies
3. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 at screening
4. Arm 1 only: participant requires initial treatment for SAA/vSAA, no matched related donor is available for allogenic hematopoietic cell transplantation (HCT) and will begin IST with antithymocyte globulin and CsA
5. Arm 2 only: refractory to at least one course of immunosuppressive therapy including horse or rabbit ATG; or ineligible for ATG treatment and refractory to CsA

Exclude criteria

1. Diagnosed as having congenital aplastic anemia (AA) (Fanconi anemia, congenital dyskeratosis, etc)
2. History of other malignancy within the past 5 years, with exceptions.
3. Aplastic anemia with hemolytic paroxysmal nocturnal hemoglobinuria (PNH) (hemolytic predominant is defined as lactate dehydrogenase (LDH) > 1.5 x the upper limit of site normal
4. Arm 1 only: Previously treated with ATG, CsA, or Alemtuzumab
5. Previously treated with PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin protein (TPO), romiplostim and other TPO-receptor
agonist (eltrombopag, etc)
6. Patients who are eligible for allogenic HCT and have an available matched related donor

Related Information

• Primary Sponsor: Murakami Contact Naoko
• Secondary ID(s): NCT05323617