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

Two Arm Bridging Study to Evaluate the Efficacy of Romiplostim in the Treatment of Adult Severe Aplastic Anemia Participants Who Are Either Previously Untreated With IST or Refractory to IST

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+)

Study Overview

• Status: Withdrawn
• Conditions: Severe Aplastic Anemia (SAA)
• Intervention / Treatment: Drug: Romiplostim; Drug: Antithymocyte Globulin; Drug: Cyclosporine A

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Previously Untreated IST; Participants with SAA/vSAA that are previously untreated with IST.	Drug: Romiplostim; Administered as a subcutaneous injection.; Other Names: Nplate®; Drug: Antithymocyte Globulin; Horse or rabbit antithymocyte globulin administered as an intravenous infusion.; Drug: Cyclosporine A; Administered orally.
Experimental: Arm 2: Refractory IST; Participants with SAA/vSAA that are refractory to IST.	Drug: Romiplostim; Administered as a subcutaneous injection.; Other Names: Nplate®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arms 1 and 2: proportion of participants achieving any hematologic response at 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	Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm 1: number of participants who achieve a complete response (CR) or partial response (PR) at week 14		Week 14
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: number of participants with clinically significant changes in laboratory values		24 Weeks
Arms 1 and 2: change from baseline in Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) bleeding scale at week 14	The Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto is as follows: 0: No bleeding; Petecjoae or mucosal or retinal bleeding that did not require red-cell transfusion; Melena, hematemesis, hematuria, or hemoptysis; Any bleeding that required red-cell transfusion; Retinal bleeding accompanied by visual impairment; Nonfatal cerebral bleeding; Fatal cerebral bleeding; Fatal noncerebral bleeding	Baseline and Week 14
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: 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 participant with anti-romiplostim antibodies		Prior to romiplostim administration on Weeks 1 and 13
Arms 1 and 2: number of participants with antibodies to thrombopoietin		Prior to romiplostim administration on Weeks 1 and 13

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2023
• Primary Completion (Estimated): February 25, 2025
• Study Completion (Estimated): February 25, 2025

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Severe Aplastic Anemia; SAA; Romiplostim; Very Severe Aplastic Anemia; vSAA
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Antilymphocyte Serum; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 20210112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No