Immune Thrombocytopenic Purpura
Conditions
Keywords
Persistent Immune Thrombocytopenic Purpura, Chronic Immune Thrombocytopenic Purpura
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 (100 mg PO bid or 150 mg PO bid)
DRUGPlacebo
Placebo tablet PO bid (morning and evening) over the course of 24 weeks
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 (Count of ≥50,000/µL on at Least 4 of the Last 6 Scheduled Visits Between Weeks 14 and 24) | From Week 14 to Week 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Platelet Count ≥ 50,000/µL at Week 24 | Week 24 | Platelet Count ≥ 50,000/µL at 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. | Baseline to 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. |
| Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 | Week 12 | Platelet Count ≥ 50,000/µL at Week 12 |
| Mean of the ITP Bleeding Score (IBLS) | Assessed over the 24-week study period | 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. |
| Mean of World Health Organization (WHO) Bleeding Scale | Assessed over the 24-week study period | 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. |
| Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 24. | Baseline to 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. |
Countries
Australia, Canada, Denmark, Hungary, Italy, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
76 patients were enrolled from July 2014 to April 2016
Participants by arm
| Arm | Count |
|---|---|
| Fostamatinib Recipient Fostamatinib (100 mg PO bid or 150 mg PO bid) | 51 |
| Placebo Recipient Placebo | 25 |
| Total | 76 |
Baseline characteristics
| Characteristic | Placebo Recipient | Total | Fostamatinib Recipient |
|---|---|---|---|
| Age, Continuous | 53.2 years STANDARD_DEVIATION 16 | 56.0 years STANDARD_DEVIATION 17.2 | 57.3 years STANDARD_DEVIATION 17.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 72 Participants | 48 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 | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 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 | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 21 Participants | 65 Participants | 44 Participants |
| Sex: Female, Male Female | 17 Participants | 47 Participants | 30 Participants |
| Sex: Female, Male Male | 8 Participants | 29 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 1 / 25 |
| other Total, other adverse events | 49 / 51 | 19 / 25 |
| serious Total, serious adverse events | 8 / 51 | 5 / 25 |
Outcome results
Primary
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
Time frame: From Week 14 to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | 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) | 9 Participants |
| Placebo Recipient | 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) | 0 Participants |
p-value: 0.026195% CI: [7.2, 28.1]Fisher Exact
Secondary
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.
Time frame: Assessed over the 24-week study period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostamatinib Recipient | Mean of the ITP Bleeding Score (IBLS) | 0.13 scores on a scale | Standard Deviation 0.12 |
| Placebo Recipient | Mean of the ITP Bleeding Score (IBLS) | 0.14 scores on a scale | Standard Deviation 0.1 |
p-value: 0.664295% CI: [-0.01, 0]t-test, 2 sided
Secondary
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.
Time frame: Assessed over the 24-week study period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fostamatinib Recipient | Mean of World Health Organization (WHO) Bleeding Scale | 0.61 scores on a scale | Standard Deviation 0.66 |
| Placebo Recipient | Mean of World Health Organization (WHO) Bleeding Scale | 0.46 scores on a scale | Standard Deviation 0.56 |
p-value: 0.336595% CI: [-0.2, 0.5]t-test, 2 sided
Secondary
Number of Participants With Platelet Count ≥ 50,000/µL at Week 12
Platelet Count ≥ 50,000/µL at Week 12
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 | 11 Participants |
| Placebo Recipient | Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 | 0 Participants |
Secondary
Number of Participants With Platelet Count ≥ 50,000/µL at Week 24
Platelet Count ≥ 50,000/µL at Week 24
Time frame: 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 | 0 Participants |
Secondary
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.
Time frame: Baseline to Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 12. | 4 Participants |
| Placebo Recipient | Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 12. | 0 Participants |
Secondary
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.
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fostamatinib Recipient | Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 24. | 4 Participants |
| Placebo Recipient | Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 24. | 0 Participants |