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

Sponsor

Amgen (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05323617

Collaborator

(none)

Enrollment

Arms

17.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Romiplostim has been used in clinical trials for the treatment of severe aplastic anemia (SAA) 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 non-Asian participants with SAA.

The primary objectives of this study are to:

Arm 1: evaluate the efficacy of romiplostim and immunosuppressive therapy (IST) in adult non-Asian severe aplastic anemia (SAA) participants who are previously untreated with IST (1L)

Arm 2: evaluate the efficacy of romiplostim treatment in adult non-Asian SAA participants who are refractory to IST (2L+)

Condition or Disease	Intervention/Treatment	Phase
Severe Aplastic Anemia (SAA)	Drug: Romiplostim Drug: Antithymocyte Globulin Drug: Cyclosporine A	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Two Arm Bridging Study to Evaluate the Efficacy of Romiplostim in the Treatment of Non-Asian Adult Severe Aplastic Anemia (SAA) Subjects Who Are Either Previously Untreated With Immunosuppressive Therapy (IST) or Refractory to IST

Anticipated Study Start Date :

Jul 31, 2022

Anticipated Primary Completion Date :

Jan 26, 2024

Anticipated Study Completion Date :

Jan 26, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Previously Untreated IST Participants with SAA 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 that are refractory to IST.	Drug: Romiplostim Administered as a subcutaneous injection. Other Names: Nplate®

Arm

Intervention/Treatment

Experimental: Arm 1: Previously Untreated IST

Participants with SAA 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 that are refractory to IST.

Drug: Romiplostim

Administered as a subcutaneous injection.

Other Names:

Nplate®

Outcome Measures

Primary Outcome Measures

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

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 [Baseline and 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
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years at time of enrollment
Diagnosis of severe aplastic anemia (AA) or very severe AA 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: considered to require new treatment with anti-thymocyte globulin (ATG) and cyclosporine A (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
Arm 2 only: thrombocytopenia defined as a platelet count of ≤ 30 x 10⁹/L

Exclusion Criteria:

Participants with Asian ethnicity
Diagnosed as having congenital 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)