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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

AMG531

About this trial

This is an interventional treatment trial for Aplastic Anemia focused on measuring Anemia, Aplastic, Thrombopoietin, Thrombocytopenia

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Korea, Republic of

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

AMG531 (Dose 1)

AMG531 (Dose 2)

AMG531 (Dose 3)

AMG531 (Dose 4)

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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).

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).

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.

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.

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

Full Information

NCT ID

NCT02094417

First Posted

March 18, 2014

Last Updated

January 26, 2021

Sponsor

Kyowa Kirin Korea Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02094417

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

April 14, 2014 (Actual)

Primary Completion Date

April 24, 2017 (Actual)

Study Completion Date

November 7, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Kyowa Kirin Korea Co., Ltd.

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aplastic Anemia

Keywords

Anemia, Aplastic, Thrombopoietin, Thrombocytopenia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

35 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AMG531 (Dose 1)

Arm Type

Experimental

Arm Title

AMG531 (Dose 2)

Arm Type

Experimental

Arm Title

AMG531 (Dose 3)

Arm Type

Experimental

Arm Title

AMG531 (Dose 4)

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

AMG531

Intervention Description

Subcutaneous, weekly injection

Primary Outcome Measure Information:

Title

Proportion of Subjects Achieving a Platelet Response at Week 9

Description

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.

Time Frame

At week 9

Secondary Outcome Measure Information:

Title

Proportion of Subjects Achieving a Platelet Response

Description

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.

Time Frame

Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Title

Proportion of Subjects Achieving Platelet Transfusion Independency

Description

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).

Time Frame

Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Title

Proportion of Subjects Achieving Erythroid Response and/or Neutrophil Response

Description

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).

Time Frame

Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Title

Duration of Platelet Response and Time to Platelet Response

Description

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.

Time Frame

Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Title

Proportion of Subjects Achieving Tri-lineage Responses

Description

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.

Time Frame

Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 157

Title

Duration of Study Drug Discontinuation While Maintaining Stable Response

Description

The longest duration of study drug discontinuation in subjects while maintaining a stable response is summarized

Time Frame

Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Facility Information:

Facility Name

Korea, Republic of

City

Seoul

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

31474546

Citation

Lee JW, Lee SE, Jung CW, Park S, Keta H, Park SK, Kim JA, Oh IH, Jang JH. Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial. Lancet Haematol. 2019 Nov;6(11):e562-e572. doi: 10.1016/S2352-3026(19)30153-X. Epub 2019 Aug 29.

Results Reference

derived

Aplastic Anemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial