Clinical Trials Register

Summary
EudraCT Number:	2020-000130-18
Sponsor's Protocol Code Number:	1
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-03-09
Trial 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

2020-000130-18

A.3

Full title of the trial

Co-THEIA (Combination THerapy with mEthotrexate and adalImumAb for uveitis): Efficacy, safety and cost-effectiveness of methotrexate, adalimumab, or their combination in non infectious non anterior uveitis: a multicenter, randomized, parallel 3 arms, active-controlled, phase 3 open label with blinded outcome assessment study

Eficacia, seguridad y coste-efectividad del metotrexato, adalimumab, o su combinación en uveítis no anterior no infecciosa: un estudio multicéntrico, aleatorizado, paralelo de 3 brazos, con control activo, de fase 3, abierto, con evaluador cegado: Co-THEIA (CombinationTHerapy with mEthotrexate and adalImumAb for uveitis)

A.3.1

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

Eficacia, seguridad y coste-efectividad del metotrexato, adalimumab, o su combinación en uveítis no anterior no infecciosa

A.3.2

Name or abbreviated title of the trial where available

Co-THEIA

A.4.1

Sponsor's protocol code number

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	Fundación para la Inv. Biomédica Hospital Clínico San Carlos
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Instituto Carlos III
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fundación para la Investigación Biomédica del Hospital Clínico San Carlos
B.5.2	Functional name of contact point	UICEC IdICSC
B.5.3	Address:
B.5.3.1	Street Address	C/ Prof Martin Lagos s/n
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28040
B.5.3.4	Country	Spain
B.5.4	Telephone number	+349133030007360
B.5.5	Fax number	+34913303515
B.5.6	E-mail	fibucicec.hcsc@salud.madrid.org

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
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	Adalimumab
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.4	EV Substance Code	SUB20016
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	Comparator
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	Yes
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	Methotrexate
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METHOTREXATE
D.3.9.3	Other descriptive name	METHOTREXATE SODIUM
D.3.9.4	EV Substance Code	SUB03225MIG
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

Non infectious non anterior uveitis

Uveítis no infecciosas y no anteriores

E.1.1.1

Medical condition in easily understood language

Non infectious non anterior uveitis

Uveítis no infecciosas y no anteriores

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the proportion of patients achieving a Good Clinical Response by week 16 that is maintained in every study visit until week 52.

Comparar la proporción de pacientes que logran una buena respuesta clínica en la semana 16 que se mantiene en cada visita de estudio hasta la semana 52.

E.2.2

Secondary objectives of the trial

To compare the clinical components of the Good Clinical Response variable between treatment strategies (see page 71 for a complete list of the components)
To compare the proportion of patients achieving a Good Clinical Response by week 16
To compare several Patient Reported Outcomes Measures (health- and vision-related quality of life, anxiety and depression) between treatment strategies
To compare the time to relapse after week 16 between treatment strategies
To assess the safety of each treatment strategy
To assess the cost-utility and cost-effectiveness from both a Health System and a Societal perspectives of the combination therapy and the ADA monotherapy compared with MTX given alone
To identify genetic and proteomic biomarkers associated with drug response to each treatment strategy.

Comparar los componentes clínicos de la variable buena respuesta clínica entre las estrategias de tratamiento;
Comparar la proporción de pacientes que logran una buena respuesta clínica en la semana 16;
Comparar varias medidas de resultados informados por el paciente (calidad de vida relacionada con la salud y la visión, ansiedad y depresión) entre las estrategias de tratamiento;
Comparar el tiempo de recaída después de la semana 16 entre las estrategias de tratamiento;
Evaluar la seguridad de cada estrategia de tratamiento;
Evaluar coste-utilidad y coste-eficacia desde la perspectiva del Sistema de Salud y de la Sociedad de la terapia combinada y la monoterapia con ADA en comparación con la monoterapia con MTX, e;
Identificar biomarcadores genéticos y proteómicos asociados con la respuesta del fármaco a cada estrategia de tratamiento

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Biobank Substudy
We will carry out a substudy with the objective of building a public access biobank with peripheral blood derived samples to carry out future studies in uveitis.

Substudio Biobanco
Se planteará un subestudio cuyo objetivo sea la construcción de un biobanco de acceso público con muestras derivadas de sangre periférica para llevar a cabo futuros estudios sobre la uveítis.

E.3

Principal inclusion criteria

1. Subjects diagnosed with non-infectious intermediate-, posterior-, or pan-uveitis in at least one eye;
2. Adult patients (≥18 years);
3. Subjects with at least one flare of active eye inflammation in the previous 180 days before Baseline visit, defined by the presence of at least 1 of the following parameters in either eye:
a. Active chorioretinal or retinal vascular lesion, AND/OR
b. Presence of macular edema by optical coherence tomography (OCT: thickness >350 µm AND cysts or intraretinal fluid), AND/OR
c. ≥ 2+ anterior chamber cells , AND/OR
d. ≥ 2+ vitreous haze
4. Subjects with active eye inflammation at Baseline visit, defined by the presence of at least 1 of the following parameters in either eye:
a. Active chorioretinal or retinal vascular lesion, AND/OR
b. Presence of macular edema by OCT (thickness >350 µm AND cysts or intraretinal fluid), AND/OR
c. ≥ 1+ ACC, AND/OR
d. ≥ 1+ vitreous haze.

• Sujetos diagnosticados de uveítis no infecciosa intermedia, posterior o panuveítis, en al menos un ojo;
• Mayores>18 años
• Sujetos con inflamación ocular activa en los 180 días previos a la Visita Basal, definidos por la presencia de al menos 1 de los siguientes parámetros:
o Lesión vascular coriorretiniana o retiniana activa, Y/O
o Presencia de edema macular por tomografía de coherencia óptica (OCT: espesor> 350 µm Y quistes o líquido intrarretiniano) y evidencia de inflamación intraocular, Y/O
o ≥ 2+ células de la cámara anterior, Y/O
o ≥ 2+ vitritis
• Sujetos con inflamación ocular activa en la Visita Basal, definida por la presencia de al menos 1 de los siguientes parámetros en cualquiera de los ojos:
o Lesión vascular coriorretiniana o retiniana activa, Y/O
o Presencia de edema macular por tomografía de coherencia óptica (OCT: espesor> 350 µm Y quistes o líquido intrarretiniano) y evidencia de inflamación intraocular, Y/O
o ≥ 1+ CCA, Y/O
o ≥ 1+ vitritis

E.4

Principal exclusion criteria

1. Subjects with confirmed or suspected infectious uveitis, including ocular histoplasmosis syndrome
2. Subjects with previous intolerability, safety issues according to investigator criteria, AND/OR previous failure to control ocular or other inflammation with MTX
3. Subjects with previous exposure to any biological therapy at any time (excluding anti-VEGF and denosumab), including those with that have a potential or known association with progressive multifocal leukoencephalopathy (i.e. natalizumab, rituximab or efalizumab);
4. Subjects with previous exposure to synthetic immunosuppressive therapy (such as mycophenolate or cyclosporine) other than corticosteroids in the past 6 months before Baseline;
5. Subjects with chronic structural eye damage considered by the Site’s Investigator to:
a. Interfere with the measurement of any of the study outcomes, AND/OR
b. Cause eye damage regardless of the inflammatory process, AND/OR
c. Prevent the normalization of the eye structures;

• Sujetos con uveítis infecciosa confirmada o sospechada, incluido el síndrome de histoplasmosis ocular;
• Sujetos con intolerabilidad previa, problemas de seguridad Y/O fallo previo para controlar la inflamación ocular u en otra localización con MTX;
• Sujetos con exposición previa a cualquier terapia biológica en cualquier momento (excluyendo anti-VEGF), incluyendo aquellas con una asociación potencial o conocida con leucoencefalopatía multifocal progresiva (es decir, natalizumab, rituximab o efalizumab);
• Sujetos con exposición previa a la terapia inmunosupresora sintética que no sean corticosteroides en los últimos 6 meses antes del inicio del estudio;
• Sujetos con daño ocular estructural crónico en los que el Investigador considera que pueda:
 Interferir con la medición de cualquiera de los resultados del estudio, Y/O
 Causar daño ocular independientemente del proceso inflamatorio, Y/O
 Evitar la normalización de las estructuras oculares;

E.5 End points

E.5.1

Primary end point(s)

To compare the proportion of patients achieving a Good Clinical Response by week 16 that is maintained in every study visit until week 52.

Comparar la proporción de pacientes que logran una buena respuesta clínica en la semana 16 que se mantiene en cada visita de estudio hasta la semana 52.

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks

52 semanas

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

52 weeks

52 semanas

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Evaluador ciego

Blinded outcome assessment

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

Last patient last visit

Último paciente última visita

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:

140

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

192

F.4.2

For a multinational trial

F.4.2.1

In the EEA

192

F.4.2.2

In the whole clinical trial

192

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

2020-10-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-18

P. End of Trial
P.	End of Trial Status	Ongoing

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