Clinical Trials Register

Summary
EudraCT Number:	2019-001882-34
Sponsor's Protocol Code Number:	C-935788-058
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-12-02
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

Spain - AEMPS

A.2

EudraCT number

2019-001882-34

A.3

Full title of the trial

A Phase 3 Open Label Extension Study of Fostamatinib Disodium in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia

Estudio de extensión abierto de fase III del fostamatinib disódico en el tratamiento de la anemia hemolítica autoimmune por anticuerpos calientes

A.3.1

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

This is a Phase 3 multi-center, open-label extension study to evaluate the long-term safety and efficacy of fostamatinib (R788) in subjects with wAIHA who have completed 24 weeks of participation in study C-935788-057.

Estudio de extensión abierto y multicéntrico de fase III para evaluar la eficacia y seguridad a largo plazo del fostamatinib(R788) en pacientes con anemia hemolítica autoimmune por anticuerpos calientes que han completado 24 semanas de su participación en el estudio C-935788-057.

A.4.1

Sponsor's protocol code number

C-935788-058

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	Pharm-Olam International (Spain) S.L.U
B.5.2	Functional name of contact point	Regulatory Department
B.5.3	Address:
B.5.3.1	Street Address	C/Antracita, 7 Planta 1 A Nave 6
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28045
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34 91-145 91 10
B.5.5	Fax number	+34 91-434-27 73
B.5.6	E-mail	regulatory.spain@pharm-olam.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
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
D.3.9.1	CAS number	914295-16-2
D.3.9.2	Current sponsor code	Fostamatinib Disodium R935788
D.3.9.3	Other descriptive name	R788, fostamatinib disodium hexahydrate (in USPI/FPI)
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
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
D.3.9.1	CAS number	914295-16-2
D.3.9.2	Current sponsor code	Fostamatinib Disodium R935788
D.3.9.3	Other descriptive name	R788, fostamatinib disodium hexahydrate (in USPI/FPI)
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Warm antibody autoimmune hemolytic anemia (wAIHA)

Anemia hemolítica autoinmune por anticuerpos calientes (AHAIc)

E.1.1.1

Medical condition in easily understood language

Autoimmune hemolytic anemia (AIHA) is an acquired disorder manifested by autoantibody- mediated red blood cell (RBC) destruction.

La anemia hemolítica autoinmune (AHAI) es un trastorno adquirido que se manifiesta por la destrucción de los glóbulos rojos mediada por autoanticuerpos.

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10003825
E.1.2	Term	Autoimmune hemolytic anemia
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 evaluate the long-term safety of fostamatinib in subjects with warm antibody autoimmune hemolytic anemia (wAIHA)

El objetivo principal del presente estudio es:
• Evaluar la seguridad a largo plazo del fostamatinib en pacientes con anemia hemolítica autoinmune (AHAI) por anticuerpos calientes

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are:
• To estimate the efficacy of fostamatinib in subjects with warm antibody autoimmune hemolytic anemia (wAIHA)
• To estimate the durability of response in subjects receiving fostamatinib for wAIHA
• To assess steroid use in subjects with warm antibody autoimmune hemolytic anemia (wAIHA) treated with fostamatinib.

Los objetivos secundarios del presente estudio son:
• Estimar la eficacia del fostamatinib en pacientes con AHAI por anticuerpos calientes
• Estimar la duración de la respuesta en pacientes que reciben fostamatinib para tratar la AHAI por anticuerpos calientes
• Evaluar el uso de corticoesteroides en pacientes con AHAI por anticuerpos calientes tratados con fostamatinib.

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 completed all 24 weeks of participation in the study C-935788-057.
3. Female subjects must be either post-menopausal for at least 1 year or surgically sterile; or, if of childbearing potential, must not be pregnant or lactating and must agree to use a highly effective method of birth control throughout the duration of the trial and for 14 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 baseline an intrauterine device (IUD), or intrauterine hormone-releasing system (IUS), or true abstinence (i.e. abstinence is in line with the preferred and usual lifestyle of the subject).
4. 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.

1. Los pacientes deberán estar dispuestos y en la capacidad de otorgar su consentimiento informado por escrito, mediante la firma de un Documento de consentimiento informado aprobado por un comité de ética, antes de la realización de cualquier procedimiento propio del estudio.
2. Los pacientes deberán haber concluido la totalidad de las 24 semanas de participación en el estudio C-935788-057.
3. Las pacientes deberán encontrarse en período postmenopáusico por lo menos durante un año o haberse sometido a esterilización quirúrgica. En el caso de las pacientes con capacidad de quedar embarazadas, no deberán estar embarazadas o en período de lactancia y deberán aceptar utilizar un método anticonceptivo muy eficaz en el transcurso del ensayo y durante los 14 días siguientes a la administración de la última dosis. Los métodos anticonceptivos aceptables son: métodos anticonceptivos hormonales (píldora, inyección o implante) utilizados de forma continua durante un mínimo de 30 días antes de la visita basal, dispositivo intrauterino (DIU) o sistema intrauterino (SIU) liberador de un tratamiento anticonceptivo hormonal, o abstinencia verdadera (es decir, la abstinencia está en concordancia con la forma de vida preferida y habitual de la paciente).
4. A juicio del investigador, el paciente es capaz de entender la naturaleza del estudio y los riesgos de la participación, así como de comunicarse de forma satisfactoria con el investigador.

E.4

Principal exclusion criteria

1. Any subject who discontinued participation in Study C-935788-057 prior to Week 24.

1. Pacientes que hayan dejado de participar en el estudio C-935788-057 antes de la semana 24.

E.5 End points

E.5.1

Primary end point(s)

Safety Endpoints:
• Adverse events
• Changes from baseline in selected laboratory values per CTCAE criteria V 5.0
• Changes from baseline in blood pressure over time

Efficacy Endpoints:
• Durable hemoglobin response (Yes/No) within 24 weeks of treatment
A hemoglobin response is defined as a hemoglobin level of >10 g/dL and ≥2 g/dL higher than the baseline (i.e, hemoglobin value prior to fostamatinib exposure), during the previous 4 weeks, the steroid dose is not higher than the baseline level, and rescue medication is not administered. A durable response is defined as a hemoglobin response on at least 3 scheduled visits during the first 24 weeks of this study.
• Hemoglobin response at 48 weeks (Yes/No) defined as subjects who achieve a durable response, as above, and have a hemoglobin response at 48 weeks
• Hemoglobin response by week 24
• Partial hemoglobin response, defined as a Hgb change from baseline of ≥2 g/dL
• Subjects who achieve steroid dose < 10 mg/day (prednisone equivalent)
• Change from baseline in hemoglobin values over time
• Change from baseline in steroid dose
• Subjects requiring any rescue during this study
• Overall duration of response and duration of first response
• Subjects who decrease any concomitant wAIHA therapy

Criterios de valoración de la seguridad:
• Acontecimientos adversos
• Cambios con respecto a los valores basales en las pruebas analíticas seleccionadas, según los criterios terminológicos comunes para acontecimientos adversos (CTCAE) V 5.0
• Cambios con respecto al valor basal en la presión arterial en el transcurso del tiempo

Criterios de valoración de la eficacia:
• Respuesta hemoglobínica duradera (sí/no) en las 24 semanas de tratamiento
Una respuesta hemoglobínica se define como un valor de hemoglobina >10 g/dl y a su vez superior en ≥2 g/dl al valor basal (es decir, el valor de hemoglobina antes de la exposición al fostamatinib) si, durante las 4 semanas anteriores, la dosis de corticoesteroides no se incrementó respecto al nivel basal y no se administró tratamiento de rescate). Una respuesta duradera se define como una respuesta hemoglobínica presente en por lo menos tres visitas programadas en el transcurso de las 24 semanas de duración de este estudio.
• Respuesta hemoglobínica a las 48 semanas (sí/no), definida como pacientes con una respuesta duradera, como se definió antes, y una respuesta hemoglobínica a las 48 semanas.
• Respuesta hemoglobínica en la semana 24
• Respuesta hemoglobínica parcial, definida como un cambio en el valor de la hemoglobina ≥2 g/dl con respecto al valor basal
• Pacientes que alcanzan una dosis de corticoesteroides <10 mg/día (prednisona o equivalente)
• Cambio en el transcurso del tiempo en los valores de hemoglobina con respecto al valor basal
• Cambio en la dosis de corticoesteroides con respecto a la dosis basal
• Pacientes que necesiten algún tratamiento de rescate a lo largo de este estudio
• Duración global de la respuesta y duración de la primera respuesta
• Pacientes a quienes se les haya disminuido algún medicamento concurrente para la AHAI por anticuerpos calientes

E.5.1.1

Timepoint(s) of evaluation of this end point

24 week evaluation

Semana 24 de evaluación

E.5.2

Secondary end point(s)

None

Ninguno

E.5.2.1

Timepoint(s) of evaluation of this end point

None

Ninguno

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

Australia

Austria

Belarus

Belgium

Bulgaria

Canada

Czech Republic

Denmark

France

Georgia

Germany

Hungary

Italy

Netherlands

Norway

Romania

Russian Federation

Serbia

Spain

Ukraine

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

LVLS

Última visita del último paciente

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

E.8.9.2

In all countries concerned by the trial days

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)

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)

None

Ninguno

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

2020-01-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-12-17

P. End of Trial
P.	End of Trial Status	Completed

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