An open-label safety study of S-888711 in adult subjects with relapsed persistent or chronic immune thrombocytopenia with or without prior splenectomy

• Conditions: Relapsed persistent or chronic immune thrombocytopenia with or without prior splenectomy; MedDRA version: 12.1Level: LLTClassification code 10066667Term: Chronic thrombocytopenia; MedDRA version: 12.1Level: LLTClassification code 10063129Term: Persisting thrombocytopenia

• Registration Number: EUCTR2009-017942-30-FR
• Lead Sponsor: Shionogi USA, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-22
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Subjects who previously participated in the Phase 2 ITP Study 0913M0621 and who either completed treatment or discontinued treatment due to a platelet count > 400, 000/µL and must also meet all inclusion criteria listed below, including platelet counts < 50,000/µL to be eligible for study participation:

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, exclusively progestin-based and/or 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 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) and have a platelet count < 30,000/µL if not taking medications or < 50,000/µL despite concomitant steroids or other ITP therapies, such as danazol or immunosuppressive drugs.
7. Subjects receiving chronic maintenance steroid therapy must have received a stable dose (same milligram amount ± 10%) for at least 2 weeks prior to Screening.
8. Prothrombin time (PT) and activated partial thromboplastin time (APTT) within 20% of the upper limit of normal at Screening.
9. Subjects receiving stable dosages of cyclosporine A, mycophenolate mofetil,
azathioprine, or danazol are allowed. The dosages of all these medications must be stable for at least 4 weeks prior to Visit 1 (Day 1).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject will not be eligible for study participation if he/she meets any of 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 initial Screening Visit.
4. Use of the following drugs or treatment prior to 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 initial Screening Visit.
6. Splenectomy within 4 weeks prior to Initial Screening Visit.
7. 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 bone
marrow 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
8. Exposure to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665) within 4 weeks prior to initial 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, other than S-888711, within the past 4 weeks prior to the initial Screening Visit.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified