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

• Sponsor: Rigel Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02076412
• Collaborator: (none)
• Enrollment: 74
• Locations: 35
• Arms: 2
• Duration (Months): 19
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Immune Thrombocytopenic Purpura	Drug: Fostamatinib Disodium; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fostamatinib Disodium Fostamatinib Disodium tablet 100 mg or 150 mg PO bid (morning and evening) over the course of 24 weeks.	Drug: Fostamatinib Disodium; Fostamatinib Disodium tablet 100 mg or 150 mg PO bid (morning and evening) over the course of 24 weeks.; Other Names: R935788 R788 Fostamatinib
Other: Placebo Placebo tablet PO bid (morning and evening) over the course of 24 weeks	Drug: Placebo; Placebo tablet PO bid (morning and evening)

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Number of Participants With Platelet Count ≥ 50,000/µL at Week 12 [Baseline to Week 12]

   Platelet Count ≥ 50,000/µL at Week 12

2. Number of Participants With Platelet Count ≥ 50,000/µL at Week 24 [Baseline to Week 24]

   Platelet Count ≥ 50,000/µL at Week 24

3. 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.

4. 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

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology Oncology Associates of Rockland Division of Highland Medical PC	Nyack	New York	United States	10960
2	Hanusch-Krankenhaus Wiener Gebietskrankenkasse	Vienna	AU	Austria	1140
3	Medizinische Universitaet Wien / AKH Wien	Wien	AU	Austria	1090
4	LKH Feldkirch at LKH Rankweil	Rankweil		Austria	6830
5	Specialized Hospital for Active Treatment of Hematology Diseases, EAD, Sofia, Department of Chemotherapy, Hemotherapy and Blood Inherited Diseases to Clinic of Clinical Hematology;	Sofia	BG	Bulgaria	1756
6	MHAT Hristo Botev, AD, Vratsa, First Internal Department	Vratsa	BG	Bulgaria	3000
7	UMHAT Dr. Georgi Stranski, EAD, Pleven, Clinic of Hematology	Pleven		Bulgaria	5800
8	UMHAT Aleksandrovska, EAD, Clinic of Clinical Hematology	Sofia		Bulgaria	1431
9	Fakultni nemocnice Brno	Brno	CZ	Czechia	625 00
10	Hospital Kyjov	Kyjov	CZ	Czechia	69733
11	Fakultni nemocnice Ostrava	Ostrava-Poruba		Czechia	708 52
12	Fakultni nemocnice Kralovske Vinohrady	Praha 10		Czechia	100 34
13	Vseobecna fakultni nemocnice, Linterní Klinika, Klinika hematologie	Praha 2		Czechia	128 08
14	Universitaetsklinikum Giessen und Marburg (UKGM)	Giessen	DE	Germany	35392
15	Werlhof Institut GmbH	Hannover	DE	Germany	30159
16	Charit Berlin - Campus Benjamin Franklin	Berlin		Germany	12203
17	Marien Hospital Duesseldorf	Duesseldorf		Germany	40479
18	Universittsklinikum Essen	Essen		Germany	45147
19	Haukeland University Hospital	Bergen		Norway	5021
20	Sykehuset Østfold Fredrikstad	Fredrikstad		Norway	1606
21	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
22	Szpital Uniwersytecki	Krakow		Poland	31-501
23	Wojewódzki Szpital Specjalistyczny im. M. Kopernika w Łodzi	Lodz		Poland	93-510
24	Specjalistyczny Gabinet Lekarski	Lublin		Poland	20-081
25	Szpital Wojewodzki w Opolu	Opole		Poland	45-064
26	Wojewodzki Szpital Specjalistyczny im. J. Korczaka	Slupsk		Poland	76-200
27	Instytut Hematologii I Transfuzjologii	Warszawa		Poland	02-776
28	Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocrlaw	Wroclaw		Poland	50-367
29	Spitalul Clinic Judetean de Urgenta Tirgu-Mures, Sectia Medicina Interna 1, Compartiment Hematologie	Targu Mures	Mures	Romania	540136
30	Spitalul Clinic Colentina, Hematologie	Bucuresti		Romania	020125
31	Spitalul Clinic Coltea, Hematologie	Bucuresti		Romania	030171
32	Hospital Universitari Vall D'Hebron	Barcelona		Spain	08035
33	Hospital Universitari Germans Trias i Pujol	Barcelona		Spain	08916
34	Hospital Universitariola Paz	Madrid		Spain	28046
35	Hospital Universitari i Politécnic La Fe de Valencia	Valencia		Spain	46026

Sponsors and Collaborators

• Rigel Pharmaceuticals

Investigators

• Study Director: Rigel Pharmaceuticals, Inc., Rigel Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rigel Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02076412
• Other Study ID Numbers: C-935788-048; 2013-005453-76
• First Posted: Mar 3, 2014
• Last Update Posted: Jan 25, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic

Study Results

Participant Flow

Recruitment Details	74 patients were enrolled from January 2015 to August 2016

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo
Period Title: Overall Study
STARTED	50	24
COMPLETED	13	2
NOT COMPLETED	37	22

Baseline Characteristics

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient	Total
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo	Total of all reporting groups
Overall Participants	50	24	74
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.1 (15.2)	49.5 (16.5)	49.2 (15.5)
Sex: Female, Male (Count of Participants)
Female	31 62%	13 54.2%	44 59.5%
Male	19 38%	11 45.8%	30 40.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	50 100%	24 100%	74 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	50 100%	24 100%	74 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Stable Platelet Response of at Least 50,000/µL
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo
Measure Participants	50	24
Count of Participants [Participants]	9 18%	1 4.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fostamatinib Recipient
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1519
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	13.8
	Confidence Interval	(2-Sided) 95%; 0.5 to 27.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval for treatment difference (risk difference) was based on the normal approximation

2. Secondary Outcome

Title	Number of Participants With Platelet Count ≥ 50,000/µL at Week 12
Description	Platelet Count ≥ 50,000/µL at Week 12
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo
Measure Participants	50	24
Count of Participants [Participants]	12 24%	3 12.5%

3. Secondary Outcome

Title	Number of Participants With Platelet Count ≥ 50,000/µL at Week 24
Description	Platelet Count ≥ 50,000/µL at Week 24
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo
Measure Participants	50	24
Count of Participants [Participants]	8 16%	1 4.2%

4. Secondary Outcome

Title	Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo
Measure Participants	22	9
Count of Participants [Participants]	6 12%	1 4.2%

5. Secondary Outcome

Title	Number of Participants With Platelet Count ≥ 30,000/μL and at Least 20,000/μL Above Baseline at Week 24
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo
Measure Participants	22	9
Count of Participants [Participants]	3 6%	0 0%

6. Secondary Outcome

Title	Frequency and Severity of Bleeding According to the ITP Bleeding Score (IBLS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo
Measure Participants	50	24
Mean (Standard Deviation) [scores on a scale]	0.04 (0.08)	0.06 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fostamatinib Recipient, Placebo Recipient
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4927
	Comments	P-value from a two-sided two-sample t-test, testing for a difference in means between fostamatinib and placebo.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Frequency and Severity of Bleeding According to the World Health Organization (WHO) Bleeding Scale
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fostamatinib Recipient	Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo
Measure Participants	50	24
Mean (Standard Deviation) [scores on a scale]	0.26 (0.38)	0.38 (0.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fostamatinib Recipient, Placebo Recipient
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2499
	Comments	P-value from a two-sided two-sample t-test, testing for a difference in means between fostamatinib and placebo.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.32 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	24 weeks
Adverse Event Reporting Description	One patient randomized to the placebo group was given the wrong treatment kit, and was treated with fostamatinib for 2 weeks. This patient's efficacy data were analyzed with the placebo arm, but his safety data were analyzed with the fostamatinib arm.
Arm/Group Title	Fostamatinib Recipient		Placebo Recipient
Arm/Group Description	Fostamatinib (100 mg PO bid or 150 mg PO bid)		Placebo
All Cause Mortality
	Fostamatinib Recipient		Placebo Recipient
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/51 (2%)		0/23 (0%)
Serious Adverse Events
	Fostamatinib Recipient		Placebo Recipient
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/51 (9.8%)		6/23 (26.1%)
Blood and lymphatic system disorders
Thrombocytopenia	0/51 (0%)	0	3/23 (13%)	8
Infections and infestations
Bronchitis	1/51 (2%)	1	0/23 (0%)	0
Infection	0/51 (0%)	0	1/23 (4.3%)	1
Injury, poisoning and procedural complications
Contusion	1/51 (2%)	1	0/23 (0%)	0
Muscle rupture	0/51 (0%)	0	1/23 (4.3%)	1
Investigations
Platelet count decreased	1/51 (2%)	1	0/23 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma cell myeloma	1/51 (2%)	1	0/23 (0%)	0
Nervous system disorders
Transient ischaemic attack	1/51 (2%)	1	0/23 (0%)	0
Reproductive system and breast disorders
Menorrhagia	0/51 (0%)	0	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/51 (2%)	1	0/23 (0%)	0
Skin and subcutaneous tissue disorders
Petechiae	0/51 (0%)	0	1/23 (4.3%)	2
Vascular disorders
Hypertensive crisis	1/51 (2%)	1	0/23 (0%)	0
Other (Not Including Serious) Adverse Events
	Fostamatinib Recipient		Placebo Recipient
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/51 (70.6%)		18/23 (78.3%)
Blood and lymphatic system disorders
Thrombocytopenia	0/51 (0%)		3/23 (13%)
Gastrointestinal disorders
Diarrhoea	9/51 (17.6%)		3/23 (13%)
Nausea	4/51 (7.8%)		3/23 (13%)
Infections and infestations
Bronchitis	3/51 (5.9%)		0/23 (0%)
Injury, poisoning and procedural complications
Contusion	3/51 (5.9%)		0/23 (0%)
Nervous system disorders
Headache	3/51 (5.9%)		3/23 (13%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	6/51 (11.8%)		1/23 (4.3%)
Skin and subcutaneous tissue disorders
Petechiae	2/51 (3.9%)		2/23 (8.7%)
Rash	3/51 (5.9%)		1/23 (4.3%)
Vascular disorders
Haematoma	1/51 (2%)		2/23 (8.7%)
Hypertension	7/51 (13.7%)		3/23 (13%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.