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

Immune Thrombocytopenia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01129024
• Other study ID #: 0914M0622
• Status: Terminated
• Phase: Phase 2
• Start date: April 29, 2010
• Est. completion date: June 30, 2011

Study information

• Verified date: February 2021
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: June 30, 2011
• Est. primary completion date: June 30, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Lusutrombopag
tablet

Locations

Country	Name	City	State
United States	Investigator	Anaheim	California
United States	Investigator	Atlanta	Georgia
United States	Investigator	Bethesda	Maryland
United States	Investigator	Boston	Massachusetts
United States	Investigator	Boynton Beach	Florida
United States	Investigator	Cleveland	Ohio
United States	Investigator	Jacksonville	Florida
United States	Investigator	Jefferson City	Missouri
United States	Investigator	Kansas City	Missouri
United States	Investigator	Los Angeles	California
United States	Investigator	Metairie	Louisiana
United States	Investigator	New Brunswick	New Jersey
United States	Investigator	New York	New York
United States	Investigator	New York	New York
United States	Investigator	Riverdale	Georgia
United States	Investigator	Salt Lake City	Utah
United States	Investigator	San Antonio	Texas
United States	Investigator	Seattle	Washington
United States	Investigator	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	Change From Baseline in Platelet Counts at the Final Visit		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)