E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Persistent/Chronic Immune Thrombocytopenic Purpura |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067644 |
E.1.2 | Term | Immune-mediated thrombocytopenic purpura |
E.1.2 | System Organ Class | 100000004851 |
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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 |
The primary objective of this study is to assess the long term safety of fostamatinib in subjects with persistent/chronic ITP |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to establish the long-term efficacy of fostamatinib in achieving and maintaining a stable platelet count in subjects who complete the treatment phase of Study C935788-047 or Study C935788-048, and to assess the pharmacokinetic (PK) profile of fostamatinib in subjects with persistent/chronic ITP. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must be willing and able to give written informed consent by signing an IRB-approved Informed Consent Form prior to participating in any study-specific procedures.
2. Subjects must have completed the Week 24 evaluation of C-935788-047 or C-935788-048 or have discontinued early (starting at Week 12) due to lack of response. No more than 7 days may have elapsed between the last day of treatment on the Study C-935788-047 or C-935788-048 and initial dosing (Day 1) in Study C-935788-049.
3. Male or female at least 18 years of age.
4. Females must be either post-menopausal for at least 1 year or surgically sterile; or if female of child-bearing potential, must not be pregnant or lactating and must agree to use an acceptable method of birth control throughout the duration of the trial and for 30 days following the last dose. Acceptable methods of birth control are defined as: hormonal contraception (pill, injection or implant) used consistently for at least 30 days prior toenrollment, intrauterine device (IUD), double-barrier (ie, condom and spermicide, or condom and diaphragm), or complete abstinence.
5. In the Investigator’s opinion, the subject has the ability to understand the nature of the study and any hazards of participation and to communicate satisfactorily with the Investigator. |
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E.4 | Principal exclusion criteria |
1. Any subject who discontinued participation in Study C-935788-047 or Study C-935788-048 prior to Week 12 or for any reason other than lack of response. Exceptions may be considered on a case-by-case basis after consultation between the Investigator and Sponsor with the specific reason for the exception noted.
2. Subjects with poorly controlled hypertension during Study C-935788-047 or Study C-935788-048, defined as persistent or repeated systolic ≥ 140 mmHg, or diastolic ≥ 90 mmHg whether or not the subject is receiving anti-hypertensive treatment.
3. Subjects with the following laboratory abnormalities at the time of enrollment (Day 1): a leukocyte count < 2,000/μL, a neutrophil count of < 1,000/μL, lymphocyte count < 750/μL, Hgb < 10 g/dL, or transaminase levels (ALT, AST) > 1.5x ULN, bilirubin > 1.5x ULN, or estimated glomerular filtration rate (eGFR) < 30 mL/min.
4. Subjects who have a significant infection, an acute infection such as influenza, or known inflammatory process at the time of enrollment into this study.
5. Subjects who have received any blood or blood products within the 2 weeks prior to enrollment (IVIg or anti-D are allowed if used for rescue therapy). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Version 1: The first version of the primary efficacy endpoint is for the purpose of assessing efficacy among all patients while they are on active treatment in one of the prior studies, in the current extension study, or in both. This version of the primary efficacy endpoint is the achievement and maintenance of a stable platelet count defined as follows:
1) Achievement of a platelet count of at least 50,000/μL within 12 weeks of beginning active treatment.
2) Achievement of a sustained stable platelet response; defined as no two visits, at least 4 weeks apart, with a platelet count < 50,000/μL, without an intervening visit with a platelet count of ≥ 50,000/μL unrelated to rescue therapy, within a period of 12 months following initial achievement of the target platelet count (see above).
Version 2: The second version of the primary efficacy endpoint is for the purpose of a within-subject, between-study comparison of fostamatinib and placebo among subjects randomized to placebo in either of the prior studies, This version of the primary efficacy endpoint is the achievement and maintenance of a stable platelet count defined as follows:
1) Achievement of a platelet count of at least 50,000/μL within 12 weeks of beginning treatment (placebo treatment in the prior study and fostamatinib treatment in the present study) and
2) Achievement of a sustained stable platelet response; defined as no two visits, at least 4 weeks apart, with a platelet count < 50,000/ μL, without an intervening visit with a platelet count of ≥ 50,000/ μL unrelated to rescue therapy, within a period of 12 weeks following initial achievement of the target platelet count (see above). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- within 12 weeks of beginning active treatment
- within a period of 12 weeks following initial achievement of the target platelet count |
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E.5.2 | Secondary end point(s) |
• The duration of any stable platelet response.
• Proportion of subjects in whom a reduction in the dose of concomitant ITP therapy can be achieved while maintaining an adequate platelet count. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | No |
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 |
Austria |
Bulgaria |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
United States |
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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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The study will end upon completion of all protocol procedures |
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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 | 5 |
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 | 5 |
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 |