Clinical trial NCT01129024: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2010-05-24
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 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 outcomes:
measure: Duration of Response
timeFrame: 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.
measure: Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: Change From Baseline in Platelet Counts at the Final Visit
timeFrame: 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)
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Investigator
state: California
city: Los Angeles
country: United States
facility: Investigator
state: California
city: Washington
country: United States
facility: Investigator
state: District of Columbia
city: Boynton Beach
country: United States
facility: Investigator
state: Florida
city: Jacksonville
country: United States
facility: Investigator
state: Florida
city: Atlanta
country: United States
facility: Investigator
state: Georgia
city: Riverdale
country: United States
facility: Investigator
state: Georgia
city: Metairie
country: United States
facility: Investigator
state: Louisiana
city: Bethesda
country: United States
facility: Investigator
state: Maryland
city: Boston
country: United States
facility: Investigator
state: Massachusetts
city: Jefferson City
country: United States
facility: Investigator
state: Missouri
city: Kansas City
country: United States
facility: Investigator
state: Missouri
city: New Brunswick
country: United States
facility: Investigator
state: New Jersey
city: New York
country: United States
facility: Investigator
state: New York
city: New York
country: United States
facility: Investigator
state: New York
city: Cleveland
country: United States
facility: Investigator
state: Ohio
city: San Antonio
country: United States
facility: Investigator
state: Texas
city: Salt Lake City
country: United States
facility: Investigator
state: Utah
city: Seattle
country: United States
facility: Investigator
state: Washington
Study officials:
affiliation: Shionogi
name: Shionogi Clinical Trials Administrator Clinical Support Help Line
role: STUDY_DIRECTOR
References: