Relapsed persistent or chronic immune thrombocytopenia with or without prior splenectomy. MedDRA version: 12.1 Level: LLT Classification code 10066667 Term: Chronic thrombocytopenia MedDRA version: 12.1 Level: LLT Classification code 10063129 Term: Persisting thrombocytopenia
Conditions
Sponsors
Shionogi USA, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for study participation if he/she meets the following criteria: 1. A signed and dated written informed consent obtained prior to the performance of Screening procedures. 2. Males and females = 18 years of age prior to Screening. 3. All subjects must agree to use exclusively progestin-based and/or barrier method contraception if engaging in sexual intercourse. Female subjects of child bearing potential must not be breast-feeding and must use a reliable barrier method for at least 7 days prior to the first dose of study drug and continuing throughout the study until 6 weeks after the last dosing, except if surgically sterilized or have been post-menopausal for at least 12 months. Hormone based contraceptives (e.g., pills, patch, shots, implants) that are not exclusively progestin-based are prohibited. Male subjects should either remain abstinent or use a condom during the time interval between taking the first dose and 6 weeks following the last study drug dose. 4. Diagnosis of ITP by American Society of Hematology criteria for at least 12 weeks prior to Screening. 5. Subjects > 60 years of age must have had a diagnostic bone marrow aspiration within 1 year prior to Screening showing normal or increased numbers of megakaryocytes. 6. Relapsed persistent or chronic ITP status, with or without prior splenectomy, after having failed at least 1 prior ITP therapy (excluding TPO agonists) and have a platelet count =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for study participation if he/she meets any of the exclusion criteria, or will be discontinued at the discretion of the investigator if he/she develops one or more of the following exclusion criterion during the study: 1. History of inherited or acquired, clinically important hemorrhagic clotting disorder. 2. Females who are pregnant or lactating, or are receiving other hormone/chemical contraceptives that are not exclusively progestin-based. 3. History of alcohol/drug abuse or dependence within 1 year of Screening. 4. Use of the following drugs or treatment prior to Visit 1 (Day 1): • Within 1 week – Rho(D) immune globulin or intravenous immunoglobulin (IVIG); • 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; 5. History of clinically significant (in the opinion of the investigator) cardiovascular or thromboembolic disease within 26 weeks prior to Screening Visit. 6. Splenectomy within 4 weeks prior to Screening. 7. Laboratory abnormalities: • Hemoglobin 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 (HIV) positive; • Hepatitis A IgM antibody (IgM HAV) positive, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV) positive; • Thyroid stimulating hormone (TSH) > 1.5 x upper limit of normal; • Free thyroxine (T4) > 1.5 x upper limit of normal. 8. Exposure to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665) within 4 weeks prior to Screening Visit. 9. Subjects unresponsive, defined as the inability to attain adequate platelet count despite optimal dosing of previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665), based on investigator’s discretion. 10. Exposure to an investigative medication within the past 4 weeks prior to Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of three dose levels of S-888711 (0.50 mg, 0.75 mg, and 1.0 mg) and placebo on platelet count.;Secondary Objective: To assess the: - safety of S-888711; - pharmacokinetic (PK) profile of S-888711 using sparse PK sampling; - PK profile of S-888711 using serial PK sampling in a selected subset of subjects; - pharmacodynamic (PD) effect of S-888711 on platelet count and markers of platelet function, such as endogenous thrombopoietin (TPO); - PK/PD relationship of S-888711 with respect to platelet count; and - impact of S-888711 on the incidence and severity of bleeding. ;Primary end point(s): The primary assessments of efficacy are platelet counts (collected as part of the complete blood count and bleeding evaluation). For this study, subjects will be classified as responders if they: • achieve a platelet count of = 50,000/µL after 6 weeks of dosing; or • are prematurely withdrawn due to a platelet count > 400,000/µL prior to Day 42. Subjects who do not meet the above condition, have received rescue medications during the Double-Blind Treatment Period, or are withdrawn for any reasons other than a platelet count > 400,000/µL will be counted as non-responders. The primary efficacy endpoint is the proportion of responder subjects in each treatment group. | — |
Countries
France, Germany, Hungary, Italy, United Kingdom
Outcome results
None listed