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An Open-label Safety Study of Lusutrombopag (S-888711) in Adults With Chronic Immune Thrombocytopenia (ITP)

Primary Purpose

Immune Thrombocytopenia

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lusutrombopag
Sponsored by
Shionogi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Immune Thrombocytopenia focused on measuring Splenectomy, Low Platelet Count, Thrombopoiesis, Thrombocytopaenia, Idiopathic Thrombocytopenic Purpura, Immune Thrombocytopenia (ITP), Thrombotic Thrombocytopenic Purpura (ITP), Hematologic Disease, Auto-immune Thrombocytopenic Purpura, S-888711, Blood Platelet Disorders, Relapsed Persistent or Chronic ITP, ITP

Eligibility Criteria

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

Inclusion Criteria:

  • Subjects who previously participated in Study 0913M0621 (NCT01054443) and who completed treatment or discontinued treatment due to a platelet count > 400,000/μL and continued to meet all inclusion criteria of the previous study, listed below, including platelet counts < 50,000/μL were eligible for study participation. For the purpose of this study, initial screening visit and all prestudy time period refer to Study 0913M0621.
  • A signed and dated written informed consent
  • Males and females ≥ 18 years of age
  • All subjects must agree to use barrier contraception
  • Diagnosis of ITP
  • Subjects > 60 years must have had a diagnostic bone marrow aspiration
  • Relapsed persistent or chronic ITP status, with or without prior splenectomy
  • Subjects receiving steroid therapy must be on a stable dose for at least 2 weeks prior to Screening
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) within 20% of the upper limit of normal (ULN) at Screening
  • Subjects receiving stable dosages of cyclosporine A, mycophenolate mofetil, azathioprine, or danazol are allowed

Exclusion Criteria:

  • History of clinically important hemorrhagic clotting disorder
  • Females who are pregnant, lactating, or taking oral contraceptives
  • History of alcohol/drug abuse or dependence within 1 year

  • Use of the following drugs or treatment prior to Visit 1 (Day 1):

    • Within 1 week - Rho(D) immune globulin or intravenous immunoglobulin;
    • Within 2 weeks - plasmaphoresis treatment;
    • Within 4 weeks - use of anti-platelet or anti-coagulant drugs;
    • Within 8 weeks - rituximab;
    • Within 12 weeks - alemtuzumab, multi-drug systemic chemotherapy, stem cell therapy;
  • History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Initial Screening
  • Splenectomy within 4 weeks prior to Initial Screening

  • Clinically significant laboratory abnormalities

    • Hemoglobin < 10.0 g/dL for men or women, not clearly related to ITP
    • Absolute neutrophil count < 1000/mm3
    • Abnormal peripheral blood smear with evidence of fibrosis confirmed by bonemarrow biopsy
    • Total bilirubin > 1.5 x upper limit of normal
    • Alanine aminotransferase (ALT) > 1.5 x upper limit of normal
    • Aspartate aminotransferase (AST) > 1.5 x upper limit of normal
    • Creatinine > 1.5 x upper limit of normal
    • Human immunodeficiency virus positive
    • Hepatitis A IgM antibody positive, hepatitis B surface antigen or hepatitis C antibody positive
  • Exposure to previous thrombopoietin (TPO) mimetics/agonists (e.g., eltrombopag,romiplostim, E5501 [AKR-501] or LGD-4665) within 4 weeks prior to Initial Screening
  • Subjects unresponsive to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665)
  • Exposure to an investigative medication within 4 weeks prior to the initial Screening Visit

Sites / Locations

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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lusutrombopag

Arm Description

Participants received lusutrombopag 0.5 mg administered orally once a day for up to 3 years or until study termination. The dose was adjusted based on platelet counts. If a subject's platelet count remained < 50,000/μL, the dose could have been increased by 0.25 mg up to a maximum dose of 2.0 mg.

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events
An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product during the course of a clinical investigation, including any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product (IP), whether or not thought to be related to the IP. AEs reported after initial study drug administration were considered treatment-emergent. A serious adverse event is defined as any AE that resulted in death, was life-threatening, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect or an important medical event that, based upon medical judgment, may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. A treatment-related AE is any AE determined by the investigator to be possibly related, probably related, or definitely related to study drug.

Secondary Outcome Measures

Duration of Response
Duration of response was defined as the percentage of the cumulative time a platelet count was ≥ 50,000 cells/µL during the extension study.
Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period
Bleeding assessments were performed by the Investigator according to the World Health Organization (WHO) criteria bleeding scale: Grade 0: no bleeding; Grade 1: petechial bleeding; Grade 2: mild blood loss (clinically significant); Grade 3: gross blood loss, requires transfusion (severe); Grade 4: debilitating blood loss, retinal or cerebral associated with fatality. For each participant, the most severe WHO bleeding grade observed during the treatment period is reported.
Percentage of Participants Who Achieved a Platelet Count of < 50,000 Cells/μL, Between 50,000 to 400,000 Cells/μL, and ≥ 400,000 Cells/μL
This analysis includes platelet counts measured during the treatment period, including while participants were taking rescue medications.
Percentage of Participants Who Achieved a Platelet Count of < 50,000 Cells/μL, Between 50,000 to 400,000 Cells/μL, and ≥ 400,000 Cells/μL Without Rescue Medication
This analysis excludes platelet counts measured while the participant was taking rescue medications and during the 4 weeks after rescue medication.
Change From Baseline in Platelet Counts at the Final Visit

Full Information

First Posted
May 7, 2010
Last Updated
February 24, 2021
Sponsor
Shionogi
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1. Study Identification

Unique Protocol Identification Number
NCT01129024
Brief Title
An Open-label Safety Study of Lusutrombopag (S-888711) in Adults With Chronic Immune Thrombocytopenia (ITP)
Official Title
An Open-label Safety Study of S-888711 in Adult Subjects With Relapsed Persistent or Chronic Immune Thrombocytopenia With or Without Prior Splenectomy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated due to cessation of clinical development of S-888711 for chronic ITP based on a business decision by the Sponsor.
Study Start Date
April 29, 2010 (Actual)
Primary Completion Date
June 30, 2011 (Actual)
Study Completion Date
June 30, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shionogi

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of this study was to assess the long-term safety of lusutrombopag in the treatment of adults with relapsed persistent or chronic ITP with or without prior splenectomy.
Detailed Description
This was an open-label, long-term safety study of lusutrombopag in the treatment of adults with relapsed persistent or chronic ITP with or without prior splenectomy. Patients who participate in this study must have completed the Phase 2 study 0913M0621 (NCT01054443), a double-blind, placebo controlled, parallel group study that evaluated the efficacy and safety lusutrombopag during which they either completed treatment or discontinued treatment due to a platelet count > 400,000/μL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune Thrombocytopenia
Keywords
Splenectomy, Low Platelet Count, Thrombopoiesis, Thrombocytopaenia, Idiopathic Thrombocytopenic Purpura, Immune Thrombocytopenia (ITP), Thrombotic Thrombocytopenic Purpura (ITP), Hematologic Disease, Auto-immune Thrombocytopenic Purpura, S-888711, Blood Platelet Disorders, Relapsed Persistent or Chronic ITP, ITP

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lusutrombopag
Arm Type
Experimental
Arm Description
Participants received lusutrombopag 0.5 mg administered orally once a day for up to 3 years or until study termination. The dose was adjusted based on platelet counts. If a subject's platelet count remained < 50,000/μL, the dose could have been increased by 0.25 mg up to a maximum dose of 2.0 mg.
Intervention Type
Drug
Intervention Name(s)
Lusutrombopag
Other Intervention Name(s)
MULPLETA®, S-888711
Intervention Description
tablet
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product during the course of a clinical investigation, including any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product (IP), whether or not thought to be related to the IP. AEs reported after initial study drug administration were considered treatment-emergent. A serious adverse event is defined as any AE that resulted in death, was life-threatening, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect or an important medical event that, based upon medical judgment, may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. A treatment-related AE is any AE determined by the investigator to be possibly related, probably related, or definitely related to study drug.
Time Frame
From first dose of study drug in the extension study up to 6 weeks after last dose; median (range) time on study treatment was 148 (10-387) days.
Secondary Outcome Measure Information:
Title
Duration of Response
Description
Duration of response was defined as the percentage of the cumulative time a platelet count was ≥ 50,000 cells/µL during the extension study.
Time Frame
From first dose of study drug in the extension study up to 6 weeks after last dose; median (range) time on treatment was 148 (10 - 387) days.
Title
Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period
Description
Bleeding assessments were performed by the Investigator according to the World Health Organization (WHO) criteria bleeding scale: Grade 0: no bleeding; Grade 1: petechial bleeding; Grade 2: mild blood loss (clinically significant); Grade 3: gross blood loss, requires transfusion (severe); Grade 4: debilitating blood loss, retinal or cerebral associated with fatality. For each participant, the most severe WHO bleeding grade observed during the treatment period is reported.
Time Frame
Bleeding assessments were performed at Weeks 1, 2, 3, 4, 5, and 6, Months 1, 2, 3, 6, 9, and 12, and every 3 months thereafter until end of treatment; median (range) time on treatment was 148 (10-387) days.
Title
Percentage of Participants Who Achieved a Platelet Count of < 50,000 Cells/μL, Between 50,000 to 400,000 Cells/μL, and ≥ 400,000 Cells/μL
Description
This analysis includes platelet counts measured during the treatment period, including while participants were taking rescue medications.
Time Frame
Platelets were assessed at Weeks 1, 2, 3, 4, 5, and 6, Months 1, 2, 3, 6, 9, and 12, and every 3 months thereafter, until end of treatment; median (range) time on treatment was 148 (10-387) days.
Title
Percentage of Participants Who Achieved a Platelet Count of < 50,000 Cells/μL, Between 50,000 to 400,000 Cells/μL, and ≥ 400,000 Cells/μL Without Rescue Medication
Description
This analysis excludes platelet counts measured while the participant was taking rescue medications and during the 4 weeks after rescue medication.
Time Frame
Platelets were assessed at Weeks 1, 2, 3, 4, 5, and 6, Months 1, 2, 3, 6, 9, and 12, and every 3 months thereafter, until end of treatment; median (range) time on treatment was 148 (10-387) days.
Title
Change From Baseline in Platelet Counts at the Final Visit
Time Frame
Baseline and the final visit (If a subject had multiple platelet count measurements for the specific dose level due to dose adjustments, the final platelet count was used)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects who previously participated in Study 0913M0621 (NCT01054443) and who completed treatment or discontinued treatment due to a platelet count > 400,000/μL and continued to meet all inclusion criteria of the previous study, listed below, including platelet counts < 50,000/μL were eligible for study participation. For the purpose of this study, initial screening visit and all prestudy time period refer to Study 0913M0621. A signed and dated written informed consent Males and females ≥ 18 years of age All subjects must agree to use barrier contraception Diagnosis of ITP Subjects > 60 years must have had a diagnostic bone marrow aspiration Relapsed persistent or chronic ITP status, with or without prior splenectomy Subjects receiving steroid therapy must be on a stable dose for at least 2 weeks prior to Screening Prothrombin time (PT) and activated partial thromboplastin time (aPTT) within 20% of the upper limit of normal (ULN) at Screening Subjects receiving stable dosages of cyclosporine A, mycophenolate mofetil, azathioprine, or danazol are allowed Exclusion Criteria: History of clinically important hemorrhagic clotting disorder Females who are pregnant, lactating, or taking oral contraceptives History of alcohol/drug abuse or dependence within 1 year Use of the following drugs or treatment prior to Visit 1 (Day 1): Within 1 week - Rho(D) immune globulin or intravenous immunoglobulin; Within 2 weeks - plasmaphoresis treatment; Within 4 weeks - use of anti-platelet or anti-coagulant drugs; Within 8 weeks - rituximab; Within 12 weeks - alemtuzumab, multi-drug systemic chemotherapy, stem cell therapy; History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Initial Screening Splenectomy within 4 weeks prior to Initial Screening Clinically significant laboratory abnormalities Hemoglobin < 10.0 g/dL for men or women, not clearly related to ITP Absolute neutrophil count < 1000/mm3 Abnormal peripheral blood smear with evidence of fibrosis confirmed by bonemarrow biopsy Total bilirubin > 1.5 x upper limit of normal Alanine aminotransferase (ALT) > 1.5 x upper limit of normal Aspartate aminotransferase (AST) > 1.5 x upper limit of normal Creatinine > 1.5 x upper limit of normal Human immunodeficiency virus positive Hepatitis A IgM antibody positive, hepatitis B surface antigen or hepatitis C antibody positive Exposure to previous thrombopoietin (TPO) mimetics/agonists (e.g., eltrombopag,romiplostim, E5501 [AKR-501] or LGD-4665) within 4 weeks prior to Initial Screening Subjects unresponsive to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665) Exposure to an investigative medication within 4 weeks prior to the initial Screening Visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shionogi Clinical Trials Administrator Clinical Support Help Line
Organizational Affiliation
Shionogi
Official's Role
Study Director
Facility Information:
Facility Name
Investigator
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Investigator
City
Los Angeles
State/Province
California
ZIP/Postal Code
90272
Country
United States
Facility Name
Investigator
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Investigator
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33426
Country
United States
Facility Name
Investigator
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Investigator
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30341
Country
United States
Facility Name
Investigator
City
Riverdale
State/Province
Georgia
ZIP/Postal Code
30274
Country
United States
Facility Name
Investigator
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Investigator
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Investigator
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Investigator
City
Jefferson City
State/Province
Missouri
ZIP/Postal Code
65109
Country
United States
Facility Name
Investigator
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
Investigator
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Investigator
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Investigator
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Investigator
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Investigator
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Investigator
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Investigator
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

An Open-label Safety Study of Lusutrombopag (S-888711) in Adults With Chronic Immune Thrombocytopenia (ITP)

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