Immune Thrombocytopenic Purpura
Conditions
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).
Interventions
Fostamatinib Disodium tablet 100 mg or 150 mg PO bid (morning and evening) over the course of 24 weeks.
DRUGPlacebo
Placebo tablet PO bid (morning and evening)
Sponsors
Rigel Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Stable Platelet Response of at Least 50,000/µL | Baseline to Week 24 | Stable platelet response by Week 24 defined as a platelet count of at least 50,000/µL on at least 4 of the 6 visits between Weeks 14-24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Platelet Count ≥ 50,000/µL at Week 24 | Baseline to Week 24 | Platelet Count ≥ 50,000/µL at Week 24 |
| Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 12 | Baseline to Week 12 | Among subjects with a baseline platelet count \< 15,000/μL, achievement of a count ≥ 30,000/μL and at least 20,000/μL above baseline at Week 12. |
| Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 | Baseline to Week 12 | Platelet Count ≥ 50,000/µL at Week 12 |
| Frequency and Severity of Bleeding According to the ITP Bleeding Score (IBLS) | Baseline to Week 24 | 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. |
| Frequency and Severity of Bleeding According to the World Health Organization (WHO) Bleeding Scale | Baseline to Week 24 | 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. |
| Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 24 | Baseline to Week 24 | Among subjects with a baseline platelet count \< 15,000/μL, achievement of a count ≥ 30,000/μL and at least 20,000/μL above baseline at Week 24 |
Countries
Austria, Bulgaria, Czechia, Germany, Norway, Poland, Romania, Spain, United States
Participant flow
Recruitment details
74 patients were enrolled from January 2015 to August 2016
Participants by arm
| Arm | Count |
|---|---|
| Fostamatinib Recipient Fostamatinib (100 mg PO bid or 150 mg PO bid) | 50 |
| Placebo Recipient Placebo | 24 |
| Total | 74 |
Baseline characteristics
| Characteristic | Placebo Recipient | Total | Fostamatinib Recipient |
|---|---|---|---|
| Age, Continuous | 49.5 years STANDARD_DEVIATION 16.5 | 49.2 years STANDARD_DEVIATION 15.5 | 49.1 years STANDARD_DEVIATION 15.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 74 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 74 Participants | 50 Participants |
| Sex: Female, Male Female | 13 Participants | 44 Participants | 31 Participants |
| Sex: Female, Male Male | 11 Participants | 30 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 51 | 0 / 23 |
| other Total, other adverse events | 36 / 51 | 18 / 23 |
| serious Total, serious adverse events | 5 / 51 | 6 / 23 |
Outcome results
Primary
Number of Participants With Stable Platelet Response of at Least 50,000/µL
Stable platelet response by Week 24 defined as a platelet count of at least 50,000/µL on at least 4 of the 6 visits between Weeks 14-24
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | Number of Participants With Stable Platelet Response of at Least 50,000/µL | 9 Participants |
| Placebo Recipient | Number of Participants With Stable Platelet Response of at Least 50,000/µL | 1 Participants |
p-value: 0.151995% CI: [0.5, 27.1]Fisher Exact
Secondary
Frequency and Severity of Bleeding According to 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.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostamatinib Recipient | Frequency and Severity of Bleeding According to the ITP Bleeding Score (IBLS) | 0.04 scores on a scale | Standard Deviation 0.08 |
| Placebo Recipient | Frequency and Severity of Bleeding According to the ITP Bleeding Score (IBLS) | 0.06 scores on a scale | Standard Deviation 0.07 |
p-value: 0.492795% CI: [-0.05, 0.02]t-test, 2 sided
Secondary
Frequency and Severity of Bleeding According to the 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.
Time frame: Baseline to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostamatinib Recipient | Frequency and Severity of Bleeding According to the World Health Organization (WHO) Bleeding Scale | 0.26 scores on a scale | Standard Deviation 0.38 |
| Placebo Recipient | Frequency and Severity of Bleeding According to the World Health Organization (WHO) Bleeding Scale | 0.38 scores on a scale | Standard Deviation 0.47 |
p-value: 0.249995% CI: [-0.32, 0.09]t-test, 2 sided
Secondary
Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 12
Among subjects with a baseline platelet count \< 15,000/μL, achievement of a count ≥ 30,000/μL and at least 20,000/μL above baseline at Week 12.
Time frame: Baseline to Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 12 | 6 Participants |
| Placebo Recipient | Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 12 | 1 Participants |
Secondary
Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 24
Among subjects with a baseline platelet count \< 15,000/μL, achievement of a count ≥ 30,000/μL and at least 20,000/μL above baseline at Week 24
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 24 | 3 Participants |
| Placebo Recipient | Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 24 | 0 Participants |
Secondary
Number of Participants With Platelet Count ≥ 50,000/µL at Week 12
Platelet Count ≥ 50,000/µL at Week 12
Time frame: Baseline to Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 | 12 Participants |
| Placebo Recipient | Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 | 3 Participants |
Secondary
Number of Participants With Platelet Count ≥ 50,000/µL at Week 24
Platelet Count ≥ 50,000/µL at Week 24
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | Number of Participants With Platelet Count ≥ 50,000/µL at Week 24 | 8 Participants |
| Placebo Recipient | Number of Participants With Platelet Count ≥ 50,000/µL at Week 24 | 1 Participants |