Clinical Trials Register

Summary
EudraCT Number:	2013-005452-15
Sponsor's Protocol Code Number:	C-935788-047
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-07-01
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2013-005452-15

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase 3 Study of Fostamatinib Disodium in the Treatment Immune Thrombocytopenic Purpura

A.4.1

Sponsor's protocol code number

C-935788-047

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02076399

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Rigel Pharmaceuticals, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Rigel Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Rigel Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Ann M. Lowe, MD
B.5.3	Address:
B.5.3.1	Street Address	1180 Veterans Boulevard
B.5.3.2	Town/ city	South San Francisco
B.5.3.3	Post code	CA 94080
B.5.3.4	Country	United States
B.5.4	Telephone number	1 415 309 7672
B.5.5	Fax number	1 650 624 1282
B.5.6	E-mail	alowe@rigel.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	fostamatinib disodium tablets
D.3.2	Product code	R935788
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fostamatinib disodium
D.3.9.1	CAS number	914295-16-2
D.3.9.2	Current sponsor code	R935788 disodium hexahydrate
D.3.9.3	Other descriptive name	FOSTAMATINIB DISODIUM
D.3.9.4	EV Substance Code	SUB32625
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	fostamatinib disodium tablets
D.3.2	Product code	R935788
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	fostamatinib disodium
D.3.9.1	CAS number	914295-16-2
D.3.9.2	Current sponsor code	R935788 disodium hexahydrate
D.3.9.3	Other descriptive name	FOSTAMATINIB DISODIUM
D.3.9.4	EV Substance Code	SUB32625
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Persistent/Chronic Immune Thrombocytopenic Purpura

E.1.1.1

Medical condition in easily understood language

Thrombocytopenic Purpura

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10067644
E.1.2	Term	Immune-mediated thrombocytopenic purpura
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to establish the efficacy of fostamatinib as compared with placebo in achieving a stable platelet response in subjects with persistent/chronic ITP.

E.2.2

Secondary objectives of the trial

Secondary objectives include assessment of the incidence of bleeding complications in subjects receiving fostamatinib as compared with placebo, and assessment of the overall safety and tolerability of fostamatinib versus placebo in subjects with persistent/chronic ITP.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Subject must be willing and able to give written informed consent by signing an IRB approved Informed Consent Form prior to undergoing any study-specific procedures.
2.Subject must have had a diagnosis of ITP for at least 3 months and no known etiology for thrombocytopenia.
3.Subject’s platelet count averages < 30,000/µL (and none > 35,000 unless as a result of rescue therapy) from at least 3 qualifying counts within the preceding 3 months. At least 2 of the qualifying counts must have been taken during the screening period.
4.Must have previously received at least 1 typical regimen for the treatment of ITP. The typical regimen can include such approved agents as:
• a thrombopoietin (romiplostim, eltrombopag), unless contraindicated
• corticosteroids with or without splenectomy
• intravenous immunoglobulin
5.Male or female at least 18 years of age.
6.Performance status on Karnofsky performance status scale (KPS) > 70
7.Subject’s concurrent treatment for ITP may consist of either glucocorticoids (< 20 mg prednisone equivalent per day), or azathioprine or danazol. The dose of the concurrent medication must have been stable for 14 days prior to baseline and must be expected to remain stable throughout the study. No other concurrent medications for ITP are permitted.
8.Subject’s other therapeutic agents for ITP have been discontinued in accordance with the washout periods
9.Female subject 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 to screening, an intrauterine device (IUD), a double-barrier method (ie, condom and spermicide, or condom and diaphragm), or complete abstinence.
10.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.

E.4

Principal exclusion criteria

1.Subject with ITP associated with lymphoma, chronic lymphocytic leukemia, viral infection, autoimmune disorders, thyroid disease, human immunodeficiency virus, or hepatitis or induced or alloimmune thrombocytopenia, or thrombocytopenia associated with myeloid dysplasia.
2.Subject with autoimmune hemolytic anemia.
3.Subject has a history of or active, clinically significant, respiratory, gastrointestinal (pancreatitis), renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorders that, in the Investigator’s opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study drug.
4.Subject has had any major cardiovascular event within the 6 months prior to randomization, including but not limited to; myocardial infarction, unstable angina, cerebrovascular accident, pulmonary embolism, or New York Heart Association Class III or IV heart failure.
5.Subject has uncontrolled or poorly controlled hypertension, defined as systolic blood pressure ≥ 140 mm Hg, or diastolic blood pressure ≥ 90 mm Hg, whether or not the subject is receiving anti-hypertensive treatment. Subjects may be rescreened if the blood pressure is successfully and promptly controlled (within 30 days) using conventional anti-hypertensive therapy to achieve optimal blood pressure control (< 140/90 mmHg).
6.Subject has a history of coagulopathy including prothrombotic conditions such as Factor V Leiden, APC resistance, AT-III deficiency and lupus anticoagulant, or arterial or deep venous thrombosis within 6 months prior to randomization.
7.In subjects with deep venous thrombosis greater than 6 months prior to randomization, anticoagulants must have been discontinued for at least 30 days and subsequent D dimer must be within normal limits for the site’s local laboratory.
8.Subject has a bleeding assessment score of Grade 2 at any site by the ITP Bleeding Scale (IBLS).
9.Subject has 1 or more of the following laboratory abnormalities: leukocyte count < 2,500/µL, neutrophil count of < 1,500/µL, lymphocyte count < 750/µL, Hgb < 10 g/L without ongoing transfusion support, or transaminase levels (ALT, AST) > 1.5x ULN, total bilirubin > 2.0 mg/dL, or estimated glomerular filtration rate (eGFR) < 30 mL/min at the time of screening.
10.Subject has a significant infection, or an acute infection such as influenza, or is known to have an active inflammatory process at the time of screening and/or baseline (Day 1).
11.Subject has acute gastrointestinal symptoms at the time of screening and/or baseline (eg, nausea, vomiting, diarrhea, abdominal pain).
12.Subject has increased the dose of, or added, prescription drugs within the 2 weeks prior to Day 1, unless agent is agreed to be not clinically relevant by both the Investigator and Sponsor.
13.Subject has had positive results for HIV, HBV, or HCV by standard serologic tests.
14.Subject has received any blood or blood products within the 2 weeks prior to randomization. (IVIg or anti-rho (D) immunoglobulin (anti-D IgG) are allowed if used for rescue therapy, unless platelet count is > 30,000/µL at the time of randomization.)
15.Subject is currently enrolled in an investigational drug or device study or has used an investigational drug or device within 30 days or 5 half-lives (whichever is longer) of Day 1.
16.Subject has a history of alcohol or substance abuse that, in the judgment of the Investigator, may impair or risk the subject’s full participation in the study.
17.Subject has a known allergy and/or sensitivity to the test article or its components.
18. Subject has had major surgery within 28 days prior to randomization or has a surgical wound that is not fully healed

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is achievement of a 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.

E.5.1.1

Timepoint(s) of evaluation of this end point

visits between Weeks 14-24

E.5.2

Secondary end point(s)

The secondary efficacy endpoints of this study are as follows:
• Achievement of a platelet response (a platelet count of at least 50,000/μL) at Weeks 12 and 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 Weeks 12 and 24.
• Frequency and severity of bleeding according to the ITP Bleeding Score (IBLS) and World Health Organization (WHO) bleeding scale over the 24-week study period.

E.5.2.1

Timepoint(s) of evaluation of this end point

• at Weeks 12 and 24
• over the 24-week study period

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Denmark

Hungary

Italy

Netherlands

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The study will end upon completion of all protocol procedures

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects who successfully complete the scheduled treatment period will be offered the opportunity to receive open label fostamatinib therapy in a long-term follow-up extension study.
Non-responders may proceed to receive open-label fostamatinib in the long-term follow-up extension study, C935788-049, beginning at Week 12 provided they have received 150 mg PO bid for at least 4 weeks (unless this higher dose was not well tolerated).

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-08-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-08-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-04-15

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