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 efficacy of three dose levels of S-888711 (0.50 mg, 0.75 mg, and 1.0 mg) and placebo on platelet count. |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 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 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 < 10.0 g/dL for men or women, not clearly related to ITP; • Absolute neutrophil count < 1000/mm3; • Abnormal peripheral blood smear; • 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 (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. |
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E.5 End points |
E.5.1 | 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.
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | 2 |
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 | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 14 |
E.8.9.2 | In all countries concerned by the trial days | 0 |