A Efficacy and Safety Study of R935788 in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura (ITP)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether fostamatinib is safe and effective in the treatment of persistent/chronic Immune Thrombocytopenic Purpura (ITP).

Official Title
-----------------
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura

Conditions
-----------------
Immune Thrombocytopenic Purpura

Intervention / Treatment
-----------------
* Drug: Fostamatinib disodium
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of persistent/chronic ITP for at least 3 months. Average platelet count < 30,000/µL (and none > 35,000 unless as a result of rescue therapy) from at least 3 qualifying counts Exclusion Criteria: Clinical diagnosis of autoimmune hemolytic anemia Uncontrolled or poorly controlled hypertension History of coagulopathy including prothrombotic conditions

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fostamatinib Disodium<br>Subjects begin with Fostamatinib Disodium tablet 100 mg PO bid and increase to 150 mg big after week 4 based on platelet count and tolerability. | Drug: Fostamatinib disodium<br>* Fostamatinib (100 mg PO bid or 150 mg PO bid)<br>* Other names: Fostamatinib;|
| Other: Placebo<br>Placebo tablet PO bid (morning and evening) over the course of 24 weeks | Drug: Placebo<br>* Placebo tablet PO bid (morning and evening) over the course of 24 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Stable Platelet Response (Count of ≥50,000/µL on at Least 4 of the Last 6 Scheduled Visits Between Weeks 14 and 24) | A stable platelet response by Week 24 defined as a platelet count of at least 50,000/μL on at least 4 of the last 6 scheduled visits between Weeks 14 and 24 | From Week 14 to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 | Platelet Count ≥ 50,000/µL at Week 12 | Week 12 | 
| Number of Participants With Platelet Count ≥ 50,000/µL at Week 24 | Platelet Count ≥ 50,000/µL at Week 24 | Week 24 | 
| Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 12. | Number of subjects with baseline platelet count <15,000/μL who showed platelet count increase to ≥30,000/μL and ≥20,000/μL from baseline count at Week 12. | Baseline to Week 12 | 
| Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 24. | Number of subjects with baseline platelet count <15,000/μL who showed platelet count increase to ≥30,000/μL and ≥20,000/μL from baseline count at Week 24. | Baseline to Week 24 | 
| Mean of the ITP Bleeding Score (IBLS) | The ITP Bleeding Scale (IBLS) is an immune thrombocytopenic purpura (ITP)-specific bleeding score used to analyze the correlation of clinical and laboratory platelet variables with bleeding. The IBLS comprises of 11 grades from 0 (none) to 2 (marked bleeding) by history over the previous week or by exam; 2 being worse. These 11 grades include: skin by physical exam, oral by physical exam, skin by history, oral by history, epistaxis, gastrointestinal, urinary, gynecological, pulmonary, intracranial hemorrhage, and subconjunctival hemorrhage. After each grade is scored, the mean value for all 11 grades is calculated (lowest score being 0 and highest score being 2) for each subject visit. LOCF method was used to impute any missing data. The mean of the IBLS scores across visits during the 24-week treatment period was summarized by treatment group using descriptive statistics. A 2-sided, 2-sample t-test was used to test for a difference in means between treatments for this endpoint. | Assessed over the 24-week study period | 
| Mean of World Health Organization (WHO) Bleeding Scale | The World Health Organization (WHO) bleeding scale is a standardized grading scale created to measure the severity of bleeding. The scale is a clinical investigator-assessed five-point scale with a score range starting at the lowest 0=No bleeding, 1 = Petechiae, 2=Mild blood loss, 3=Gross blood loss, to the worse 4=Debilitating blood loss. The WHO bleeding scale is scored by history over the previous-week or by exam. After each grade is scored, the mean value is calculated (lowest score being 0 [no bleeding] to the highest score being 4 [debilitating blood loss]) for each visit. LOCF method was used to impute any missing data. The mean of the WHO bleeding scale across visits during the 24-week treatment period was summarized by treatment group using descriptive statistics. A 2-sided, 2-sample t-test was used to test for a difference in means between treatments for this endpoint. | Assessed over the 24-week study period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Persistent Immune Thrombocytopenic Purpura, Chronic Immune Thrombocytopenic Purpura