A Phase 2 Study to Evaluate the Efficacy and Safety of AMG531 in Aplastic Anemia

Aplastic Anemia Clinical Trial

Official title:

A Phase 2, Randomized, Open-Label, Parallel, Comparative, Dose-Finding Study to Evaluate the Efficacy and Safety of AMG531 in Aplastic Anemia Subjects With Thrombocytopenia Refractory to Immunosuppressive Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02094417
• Other study ID #: 531-KR001
• Status: Completed
• Phase: Phase 2
• Start date: April 14, 2014
• Est. completion date: November 7, 2017

Study information

• Verified date: April 2024
• Source: Kyowa Kirin Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The present study will be conducted to evaluate the efficacy and safety of AMG531 and to determine the recommended initial dose of AMG531 on the basis of its efficacy and safety when it is administered subcutaneously (SC) to the Aplastic Anemia (AA) patients with immunosuppressive-therapy refractory thrombocytopenia and also to assess the pharmacokinetics of this product. Its efficacy and safety during the extension period beyond one year will also be evaluated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: November 7, 2017
• Est. primary completion date: April 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Patient who is diagnosed as AA and refractory to immunosuppressive therapy

• Platelet = 30,000/µL

Exclusion Criteria:

• Concurrent active infection not adequately responding to appropriate therapy

• HIV positivity

• Bone marrow reticulin grade of > 1

• Clinically significant cardiac disease

• Arterial or venous thrombosis within the last 1 year before enrollment

• Other cause of thrombocytopenia

• AA with hemolytic predominant paroxysmal nocturnal hemoglobinuria (PNH)

• Uncontrolled diabetes

• Receiving any agent used to treat AA, including antithymocyte globulin (ATG) or ATG + cyclosporine within 6 months before starting study treatment and/or cyclosporine or anabolic hormone within 6 weeks before starting the study treatment

• History of PEG-rHuMGDF, recombinant human thrombopoietin, AMG531, and other thrombopoietin (TPO)-receptor agonist

• Who plans to conduct hematopoietic stem cell transplantation within 1 year

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• AMG531
Subcutaneous, weekly injection

Locations

Country	Name	City	State
Korea, Republic of	Korea, Republic of	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Kyowa Kirin Korea Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Subjects Achieving a Platelet Response at Week 9	The proportion of subjects achieving a platelet response at Week 9, and two-sided 95% confidence interval will be calculated. Platelet response is defined as 1) achieving absolute platelet increase of = 20x10^9/L above baseline or 2) increase to = 10x10^9/L and by at least 100% from baseline.	At week 9
Secondary	Proportion of Subjects Achieving a Platelet Response	The proportion of subjects with a platelet response in any time during the initial dose evaluation period, Week 1 through Week 12, Week 1 through Week 16, Week 1 through Week 24, Week 1 through Week 52, Week 1 through Week 104 and Week 1 through Week 156.	Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156
Secondary	Proportion of Subjects Achieving Platelet Transfusion Independency	The proportion of subjects achieving platelet transfusion independency in any time during the initial dose evaluation period , Week 1 through Week 12, Week 1 through Week 16, Week 1 through Week 24, Week 1 through Week 52, Week 1 through Week 104, and Week1 through Week 156 will be calculated in the same manner as the primary variables (The number of subjects discontinued or subjects who have missing data will not be calculated). Platelet transfusion independence is defined as achieving transfusion free period of at least 8 consecutive weeks (56 days).	Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156
Secondary	Proportion of Subjects Achieving Erythroid Response and/or Neutrophil Response	The proportion of subjects with erythroid response, neutrophil response and erythroid and/or neutrophil response in any time during the initial dose evaluation period, Week 1 through Week 12, Week 1 through Week 16, Week 1 through Week 24, Week 1 through Week 52, Week 1 through Week 104, and Week1 through Week 156 will be calculated in the same manner as the primary variables (The number of subjects discontinued or subjects who have missing data will not be calculated).	Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156
Secondary	Duration of Platelet Response and Time to Platelet Response	For subjects with a platelet response in any time, time to the initial platelet response and duration of platelet response will be summarized Time to the initial platelet response will be calculated as sampling date (response achieved) minus first dose date of study drug plus 1.; Duration of platelet response will be calculated as the maximum of the duration of platelet response for each subject, each duration of response calculated as the date when response is disappeared minus the date when response is achieved. The censoring date is defined as the date of the last Platelet examination or EOS whichever archives first.	Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156
Secondary	Proportion of Subjects Achieving Tri-lineage Responses	Tri-lineage response is defined in those achieving platelet response, erythroid response, and neutrophil response all together. The proportion of subjects with tri-lineage response will be calculated in the same manner as the primary variables. Time to tri-lineage response will be summarized in the same manner as time to platelet response. Time to tri-lineage response is defined as duration of the time from Day 1 to the date of platelet response, erythroid response or neutrophil response whichever achieves last in Visit.	Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 157
Secondary	Duration of Study Drug Discontinuation While Maintaining Stable Response	The longest duration of study drug discontinuation in subjects while maintaining a stable response is summarized	Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156