• The primary objective of this study is to assess the long term safety of fostamatinib in subjects with persistent/chronic ITP.• The secondary objectives of this study are to establish the long-term efficacy of fostamatinib in achieving and…
ID
Source
Brief title
Condition
- Platelet disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Endpoint:
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).
The beginning of active treatment may be in the prior study or in the present
extension study, depending upon when the subject first received active
treatment. Subjects who discontinue treatment due to lack of efficacy or to an
AE prior to 12 months following achievement of a platelet count of at least
50,000/µL will be considered failures. This endpoint will be summarized using
counts and percentages, together with a 95% exact (Clopper-Pearson) confidence
interval for the true percentage.
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).
Subjects who discontinue treatment due to lack of efficacy or to an AE prior to
12 weeks following achievement of a platelet count of at least 50,000/µL, will
be considered failures. The null and alternative hypotheses for the comparison
of fostamatinib vs. placebo are as H0: pF = pP vs. H1: pF * pP
where pF and pP denote the true proportions achieving and maintaining a stable
platelet count for fostamatinib and placebo, respectively. The null hypothesis
will be tested using a 2-sided McNemar*s test conducted with a significance
level of 0.05.
Secondary outcome
The secondary efficacy endpoints are as follows:
• Duration of 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.
.
Background summary
Fostamatinib is an investigational drug which is being tested for
persistenVchronic immune thrombocytopenic purpura (ITP), a disorder manifested
by immune mediated platelet destruction. ITP is a disorder that results when
your platelets are destroyed by your immune system. Your ITP is considered to
be persistenVchronic if your platelet count has regularly been below 30,000/iJL
for at least 3 months and you don't have any other conditions that are causing
your platelets to be destroyed.
The purpose of this research study is to see how effective fostamatinib is at
increasing your platelet count, by measuring whether
the number of platelets you have increases when the study drug is taken.
Study objective
• The primary objective of this study is to assess the long term safety of
fostamatinib in subjects with persistent/chronic ITP.
• 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.
Study design
This is a Phase 3 multi-center, open label extension study to evaluate the
long-term safety and the efficacy of fostamatinib in achieving and maintaining
a stable platelet response in subjects with persistent/chromic Immune
Thrombocytopenic Purpura (ITP). The study will consist of 26 visits over a
2-year period.
Eligible subjects include subjects from Study C935788-047 or Study C935788-048
who have completed the Week 24 evaluation or who discontinue early (after Week
12) due to lack of response. All subjects will receive open-label fostamatinib.
At Month 1 (Visit 2), subjects receiving fostamatinib 100 mg PO bid should have
the dose escalated to fostamatinib 150 mg PO bid if platelet count < 50,000/µL
and the study drug is well tolerated (refer to Section 7.2.1). Conversely, the
dose may be reduced at any time to a dose as low as fostamatinib 100 mg PO qd
if dose limiting AEs are observed as defined by this protocol.
During Month 2 (Visit 3), blood samples for PK analysis will be collected from
a subset of 12 subjects at selected sites. Subjects will remain at the clinic
for up to 9 hours during the visit. When a subject arrives at the clinic, the
time of the last dose of fostamatinib will be recorded in the eCRF.
During Visit 3, samples (5 mL) of whole blood will be collected at the
following timepoints:
Pre-dose and 0.5, 1, 2, 4, 6, and 8 hours post-dose.
Intervention
Subjects designated as responders (defined as platelet count >= 50,000/µL) in
the double-blind study will continue fostamatinib at their current dose and
regimen in the extension study. Subjects who enter the extension study as
non-responders (defined as platelet count < 50,000/µL) will be allocated to
fostamatinib 100 mg PO bid regardless of their original double-blind dose and
regimen. Subjects will remain blinded to their treatment assignment from the
previous study (active or placebo).
Study burden and risks
The associated benefit of treatment with fostamatinib outweighs any potential
risks for subjects participating in the study.
The safety outcomes of this study include the frequency and severity of
bleeding according to the IBLS and the WHO bleeding scale, the change from
baseline in blood pressure, liver function, and absolute neutrophil count
(ANC), the incidence of GI complaints, and the incidence of adverse events.
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Listed location countries
Age
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 Study 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 study C-935788-047 or C-935788-048 and the
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.
Exclusion criteria
1. Any subject who discontinued participation in Study C-935788-047 or 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 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).
Design
Recruitment
Medical products/devices used
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Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-005454-30-NL |
| ClinicalTrials.gov | NCT02077192 |
| CCMO | NL49121.098.14 |