Efficacy of Romiplostim in Treatment of SAA in Adults Previously Untreated With or Refractory to Immunosuppressive Therapy

Phase 2

Withdrawn

• Conditions: Severe Aplastic Anemia (SAA)
• Interventions: Drug: Romiplostim; Drug: Antithymocyte Globulin; Drug: Cyclosporine A

• Registration Number: NCT05323617
• Lead Sponsor: Amgen

Brief Summary

Romiplostim has been used in clinical trials for the treatment of severe and very severe aplastic anemia (SAA/vSAA) in Asian participants who are either previously untreated with immunosuppressive therapy (IST) or refractory to IST. This study will evaluate the efficacy of romiplostim in the treatment of participants with SAA/vSAA.

The primary objectives of this study are to:

Arm 1: Evaluate the efficacy of romiplostim and IST in adult SAA/vSAA participants who are previously untreated with IST (1L)

Arm 2: Evaluate the efficacy of romiplostim treatment in adult SAA/vSAA participants who are refractory to IST (2L+)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-05
• Study First Submitted QC: 2022-04-05
• Study First Posted: 2022-04-12
• Study Start: 2023-08-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-28
• Last Update Posted: 2023-09-29
• Primary Completion: 2025-02-25
• Study Completion: 2025-02-25

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Age ≥ 18 years at time of enrollment
• Diagnosis of SAA/vSAA confirmed by blood, bone marrow, and cytogenetic studies
• An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 at screening
• 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
• 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

Exclusion Criteria

• Diagnosed as having congenital aplastic anemia (AA) (Fanconi anemia, congenital dyskeratosis, etc)
• History of other malignancy within the past 5 years, with exceptions.
• 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
• Arm 1 only: Previously treated with ATG, CsA, or Alemtuzumab
• 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)
• Patients who are eligible for allogenic HCT and have an available matched related donor

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Previously Untreated IST	Antithymocyte Globulin	Participants with SAA/vSAA that are previously untreated with IST.
Arm 1: Previously Untreated IST	Cyclosporine A	Participants with SAA/vSAA that are previously untreated with IST.
Arm 1: Previously Untreated IST	Romiplostim	Participants with SAA/vSAA that are previously untreated with IST.
Arm 2: Refractory IST	Romiplostim	Participants with SAA/vSAA that are refractory to IST.

Primary Outcome Measures

Name	Time	Method
Arms 1 and 2: proportion of participants achieving any hematologic response at week 14	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 Measures

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