E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed persistent or chronic immune thrombocytopenia with or without prior splenectomy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066667 |
E.1.2 | Term | Chronic thrombocytopenia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063129 |
E.1.2 | Term | Persisting thrombocytopenia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the long-term safety of S-888711 |
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E.2.2 | Secondary objectives of the trial |
- Assess dose requirements for long-term platelet response - Assess durability of platelet response - Evaluate bleeding events by World Health Organization (WHO) bleeding criteria
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 showing normal or increased numbers of megakaryocytes. 6. Relapsed persistent or chronic ITP status, with or without prior splenectomy (exception: in Hungary only splenectomized subjects will be enrolled), 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). |
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E.4 | Principal 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) except if administered as rescue medication; • Within 2 weeks - platelet transfusions or plasmapheresis 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 approved TPO mimetics/agonists eltrombopag within 2 weeks or romiplostim within 4 weeks prior to dosing. 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 4 weeks prior to the initial Screening Visit.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Safety will be assessed by monitoring clinical laboratory evaluations (including hematology, blood biochemistry, urinalysis, blood smears), vital signs, physical examinations, electrocardiograms, and World Health Organization (WHO) bleeding assessments. • Treatment-emergent AEs and serious adverse events (SAEs) will be collected and tabulated. • Frequency distribution of S-888711 doses subjects receive over time • Duration of response from baseline to various timepoints, as the proportion of the cumulative time spent with a platelet count of ≥ 50,000/µL; and • Incidence and severity of bleeding associated with ITP. • The proportion of subjects who achieve a platelet count of ≥ 50,000/µL at various time intervals; • Change from baseline at various time intervals in platelet counts.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Provided in the Protocol. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |