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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-label Safety Study of S-888711 in Adult Subjects With Relapsed Persistent or Chronic Immune Thrombocytopenia With or Without Prior Splenectomy

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Lusutrombopag


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lusutrombopag<br>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. | Drug: Lusutrombopag<br>* tablet<br>* Other names: S-888711;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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