Clinical Trial Results:
A Phase 3 Open Label Extension Study of Fostamatinib Disodium in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura (ITP).
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Summary
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EudraCT number |
2013-005454-30 |
Trial protocol |
GB IT HU CZ AT NL DK ES PL BG |
Global end of trial date |
02 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jul 2021
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First version publication date |
08 Jul 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
0C-935788-049
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02077192 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Rigel Pharmaceuticals, Inc.
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Sponsor organisation address |
1180 Veterans Blvd, South San Francisco, United States, 94080
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Public contact |
Medical Information, Rigel Pharmaceuticals, Inc., +1 1-800-983-1329 , producthelp@rigel.com
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Scientific contact |
Medical Information, Rigel Pharmaceuticals, Inc., +1 1-800-983-1329 , producthelp@rigel.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Jun 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Jun 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to assess the long term safety of fostamatinib in subjects with persistent/chronic ITP
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Protection of trial subjects |
The study was conducted in accordance with Good Clinical Practices (GCP) as outlined in the International Conference on Harmonization (ICH), and the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Oct 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Norway: 2
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Country: Number of subjects enrolled |
Poland: 34
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Country: Number of subjects enrolled |
Romania: 1
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Country: Number of subjects enrolled |
Spain: 4
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Country: Number of subjects enrolled |
United Kingdom: 18
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Country: Number of subjects enrolled |
Austria: 1
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Country: Number of subjects enrolled |
Bulgaria: 12
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Country: Number of subjects enrolled |
Czechia: 10
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Country: Number of subjects enrolled |
Denmark: 1
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Country: Number of subjects enrolled |
Hungary: 2
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
United States: 17
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Country: Number of subjects enrolled |
Australia: 10
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Country: Number of subjects enrolled |
Canada: 4
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Worldwide total number of subjects |
123
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EEA total number of subjects |
74
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
95
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From 65 to 84 years |
26
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85 years and over |
2
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 124 subjects were screened from studies C788-047/ C788-048 for this extension study. Out of which, 123 subjects were enrolled and treated with study drug. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Arm title
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Fostamitinib Disodium | ||||||||||||||||||||||||
Arm description |
Fostamatinib was self-administered twice daily (bid) by orally, once in the morning and once in the evening for up to 5 years or until commercial availability of fostamatinib for all subjects, whichever occurred first, in 2 dosage strengths: 100 milligram (mg) and 150 mg. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Fostamatinib Disodium 100 mg
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Investigational medicinal product code |
R935788
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received Fostamatinib disodium 100 mg orally, twice daily (bid) (based on response to treatment in Study C-935788-047 or C-935788-048) for 5 years. Starting at Month 1, subjects receiving fostamatinib 100 mg bid had their dose escalated to fostamatinib disodium 150 mg bid if platelet count was less than (<) 50,000 per microliter (/mcL).
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Investigational medicinal product name |
Fostamatinib Disodium 150 mg
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Investigational medicinal product code |
R935788
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received Fostamatinib disodium 150 mg orally, bid (based on response to treatment in Study C-935788-047 or C-935788-048) for 5 years. Starting at Month 1, subjects receiving fostamatinib 100 mg bid had their dose escalated to fostamatinib 150 mg bid if platelet count was < 50,000 per mcL.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Baseline characteristics are analyzed with treated population data analysis set which was defined as all enrolled and treated subjects. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Fostamitinib Disodium
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Reporting group description |
Fostamatinib was self-administered twice daily (bid) by orally, once in the morning and once in the evening for up to 5 years or until commercial availability of fostamatinib for all subjects, whichever occurred first, in 2 dosage strengths: 100 milligram (mg) and 150 mg. | ||
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End point title |
Percentage of Subjects who Achieved Platelet Count of at least 50,000/MicroLiter (mcL) Within 12 Weeks of Beginning Treatment up to 12 Months (Fostamatinib in 047/048 or 049):Version 1 [1] | ||||||||
End point description |
Percentage of subjects who achieved platelet count of at least 50,000/mcL within 12 Weeks of beginning treatment up to 12 months was analyzed among all subjects who received active treatment in one of the prior studies (C788-047 or C788-048), in the current extension study (C788-049), or in both prior and current studies. Treated Population was defined as all enrolled and treated subjects.
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End point type |
Primary
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End point timeframe |
Up to 12 Months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects who Achieved Platelet Count of at least 50,000/mcL Within 12 Weeks of Beginning Treatment up to 12 Months (Placebo in 047/048 and Fostamatinib 049): Version 2 [2] | ||||||||
End point description |
A within-subject, between-study comparison of platelet counts for subjects who were previously treated with placebo in one of the prior studies (C788-047 or C788-048) was prospectively defined in the protocol (version 2). Achievement of platelet response by 12 weeks and maintenance of platelet response for 12 weeks was analyzed among subjects who had been randomized to placebo in one of the prior studies (C788-047 or C788-048). Treated Population was defined as all enrolled and treated subjects.
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End point type |
Primary
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End point timeframe |
Up to 12 Months
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Platelet Response Based on Platelet Count | ||||||||
End point description |
The duration of platelet response was defined as the time from when the subject first achieved a platelet count of at least 50,000/microliter (mcL), until the first of 2 visits with platelet counts < 50,000/mcL that were at least 4 weeks apart without an intervening visit with a platelet count less than equal to (>=) 50,000/mcL unrelated to rescue therapy. Duration of platelet response was analyzed using the Kaplan-Meier method. Treated Population was defined as all enrolled and treated subjects. Here, a number of subjects analyzed included all subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Up to 12 Months
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects in Whom a Reduction in the Dose of Concomitant ITP Therapy can be Achieved While Maintaining an Adequate Platelet Count | ||||||||
End point description |
The percentage of subjects in whom a reduction in the dose of concomitant ITP therapy could be achieved while maintaining an adequate platelet count, the reduction event was clarified to apply only to reductions in the dose of concomitant ITP therapy occurring within a period of platelet response and the reduction event was not be prompted by an adverse event.
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End point type |
Secondary
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End point timeframe |
Up to 12 Months
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to 62 months
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Fostamitinib Disodium
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Reporting group description |
Fostamatinib was self-administered twice daily (bid) by orally, once in the morning and once in the evening for up to 5 years or until commercial availability of fostamatinib for all subjects, whichever occurred first, in 2 dosage strengths: 100 milligram (mg) and 150 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Apr 2014 |
Protocol version 1.0 has been amended to protocol version 2.0 and the summary of changes are as below -
- The exclusion criteria updated and footnote added in the study procedures for better clarity
- Subjects must be willing to sign and date an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved the informed consent form (ICF) prior to participating in any study-specific screening procedure activities. Subjects will retain their same Subject ID number as per Study C-935788-047 or C-935788-048, as applicable.
- The text modified in the section of dose adjustment due to adverse events to allow for additional flexibility in study drug dose for subjects in whom the clinical benefit is shown. |
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21 Nov 2014 |
Protocol version 2.0 amended to protocol version 3.0 and summary of changes are as below -
- Revised Protocol Synopsis to include the concurrent medications and rescue therapies for more prominence
- Updated the inclusion criteria for better clarity
- Added footnote for the study procedures for better clarity
- Adverse event definition updated and
other administrative changes were made. |
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08 Nov 2016 |
The protocol version 3.0 has been amended to protocol version 4.0 and changes are as below -
• The planned duration of treatment for individual subjects was increased from 2 to 5 years or until commercial availability of fostamatinib, whichever occurred first. Note: Fostamatinib was approved in the US in April 2018.
• The visit interval for the additional treatment period (Years 3, 4, and 5) was set at every other month (as opposed to monthly for Years 1 and 2).
• The WHO bleeding scale was removed as an assessment; the bleeding assessment now uses only the Immune Thrombocytopenic Purpura Bleeding Score method.
• The provision for dose adjustments in the event of an excessive platelet response was removed.
• A provision was made for an abbreviated or “symptom-directed” physical examination during routine visits at the investigator’s discretion.
• The requirement for assessment of immunoglobulin levels every 6 months was decreased to occur just at baseline and at the end-of -study visit.
• The requirement for quality of life (QoL) assessment by 36-Item Short-Form Health Survey (SF-36) was dropped after the Month 12 visit.
• The summary table of cumulative blood volumes was removed.
• Various edits were made for clarification or consistency; these edits did not affect the subject treatment, tests, observations, or safety. |
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11 Nov 2019 |
The protocol version 4.0 amended to Protocol version 5.0, and the changes are as below -
- subjects who had no other treatment options and demonstrated benefit and tolerability to fostamatinib continued to receive study treatment; only serious adverse events (SAE) for these subjects were required to be reported to the Sponsor.
- modified the medical monitor contact information for SAE reporting
- changed the sponsor representative and signatory for the protocol. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
