Clinical Trials Register

Summary
EudraCT Number:	2011-004468-31
Sponsor's Protocol Code Number:	CT-P13-3.2
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:	2011-12-07
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

2011-004468-31

A.3

Full title of the trial

An Open-Label, Single-Arm, Extension Study to Demonstrate Long-Term Efficacy and Safety of CT-P13 When Co-administered With Methotrexate in Patients With Rheumatoid Arthritis Who Were Treated With Infliximab (Remicade or CT-P13) in Study CT-P13 3.1

Estudio de extensión abierto de un solo grupo para demostrar la eficacia y la seguridad a largo plazo de CT P13 cuando se administra junto con metotrexato en pacientes con artritis reumatoide que recibieron tratamiento con infliximab (Remicade o CT-P13) en el estudio CT-P13 3.1

A.3.1

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

Comparing the long-term effects of CT-P13 with remicade together with methotrexate in patients with arthritis

Comparar los efectos a largo plazo de CT-P13 con remicade junto con metotrexato en pacientes con artritis.

A.4.1

Sponsor's protocol code number

CT-P13-3.2

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	CELLTRION, Inc
B.1.3.4	Country	Korea, Republic of
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	CELLTRION, Inc
B.4.2	Country	Korea, Republic of
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CELLTRION, Inc
B.5.2	Functional name of contact point	Hyuk Jae Lee
B.5.3	Address:
B.5.3.1	Street Address	13-6, Songdo-dong
B.5.3.2	Town/ city	Yeonsu-gu / Incheon
B.5.3.3	Post code	406-840
B.5.3.4	Country	Korea, Republic of
B.5.4	Telephone number	8232850-5394
B.5.5	Fax number	8232850-5060
B.5.6	E-mail	HyukJae.Lee@celltrion.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	CT-P13
D.3.2	Product code	CT-P13
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Infliximab
D.3.9.1	CAS number	170277-31-3
D.3.9.2	Current sponsor code	CT-P13
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	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

Rheumatoid Arthritis

Artritis reumatoide

E.1.1.1

Medical condition in easily understood language

Arthritis

Artritis

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To confirm long-term efficacy and safety of CT-P13.

Confirmar la eficacia y la seguridad a largo plazo de CT-P13.

E.2.2

Secondary objectives of the trial

Not applicable

No aplica

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Patient who has completed the scheduled visits, including the End-of-Study Visit, in Study CT-P13 3.1.
2 Patient who has not had any major protocol violation in Study CT-P13 3.1.
3 Patient is permitted to enter the extension study if, in the opinion of their general practitioner or the investigator, the patient will continue to gain benefit from treatment in the extension study. Local guidelines for patient treatment will be followed.
4 Patient (or legal guardians, if applicable) is informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read and understand this information, and has signed and dated the written informed consent before inclusion in the extension study.
5 Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception (eg, barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], and intrauterine devices) during the course of the study and for 6 months following discontinuation of study treatment (excluding women who are not of childbearing potential and men who have been sterilized).
6 Male and female patients and their partners who have been surgically sterilized for less than 6 months prior to study entry must agree to use 2 medically accepted methods of contraception as per inclusion criterion 5.
7 Menopausal females must have experienced their last period more than 12 months prior to study entry to be classified as not of childbearing potential.

1. El paciente ha completado las visitas programadas, incluida la visita final del estudio, en el estudio CT-P13 3.1.
2. El paciente no ha tenido ninguna violación de protocolo mayor en el estudio CT-P13 3.1.
3. Se permite al paciente acceder al estudio de extensión si, en opinión de su médico de atención primaria o del investigador, seguirá beneficiándose del tratamiento en el estudio de extensión. Se seguirán las normas locales para el tratamiento de los pacientes.
4. El paciente (o en su caso, su tutor) está enteramente informado de la naturaleza y el objetivo del estudio, incluidos los posibles riesgos y efectos secundarios, se le ha dado el tiempo suficiente y la oportunidad de leer y entender esta información, y ha firmado y fechado el documento de consentimiento informado antes de su inclusión en el estudio de extensión.
5. Todos los pacientes, varones y mujeres, y sus parejas con capacidad de procrear deberán comprometerse a utilizar dos métodos anticonceptivos médicamente aceptados (p. ej., anticonceptivos de barrera [preservativo masculino, preservativo femenino, o diafragma con gel espermicida], anticonceptivos hormonales [implantes, inyectables, anticonceptivos combinados orales, parches transdérmicos, o anillos anticonceptivos] o dispositivo intrauterino) durante el estudio y durante 6 meses después de la finalización del tratamiento del estudio (se excluyen las mujeres sin capacidad de procrear y los varones que hayan sido esterilizados).
6. Los pacientes varones y mujeres y sus parejas que se hayan sometido a una esterilización por métodos quirúrgicos menos de 6 meses antes de su entrada en el estudio deberán comprometerse a utilizar dos métodos anticonceptivos médicamente aceptados, según el criterio de inclusión 5.
7. Se consideran infértiles las mujeres posmenopáusicas que han tenido su última menstruación más de 12 meses antes de la entrada en el estudio.

E.4

Principal exclusion criteria

1 Patient who has been withdrawn from Study CT-P13 3.1 for any reason.
2 Patient who, at the time of providing informed consent, has any ongoing medical issues such as serious adverse events (SAEs) or intolerance issues that mean continuation in this extension study could be detrimental to their health, in the opinion of the investigator.
3 Patient who plans to participate in a study with an investigational drug during the period of this extension study.
4 Female patient who is planning to become pregnant or breastfeed within the period of this study.
5 Patient who plans to receive a live or live-attenuated vaccination or who is scheduled to receive a live or live-attenuated vaccination during the period of this study. Killed vaccines are acceptable during the study.
6 Patient who, in the opinion of their general practitioner or investigator, should not participate in this extension study for whatever reason.
7 Patient who is receiving any surgical procedure, including bone or joint surgery or synovectomy (including joint fusion or replacement) within 12 weeks prior to the time of providing informed consent or planned within 6 months after the time of providing informed consent.
8 Patient who, at the time of providing informed consent, is taking, is planning to take, or is required to take during the course of this study any of the following concomitant medications:
- Corticosteroids, except oral glucocorticoids, of maximum equivalent daily dose of 10 mg of prednisolone. (Patients are permitted to receive low-potency topical, otic, and ophthalmic glucocorticoid preparations provided the preparations are administered per the instructions on the product label.)
- Disease-modifying antirheumatic drugs, other than methotrexate, including hydroxychloroquine, chloroquine, sulfasalazine, or leflunomide.
- Alkylating agents
- Live or live-attenuated vaccines
- Any biological agents for the treatment of RA except CT-P13 or Remicade

1. Pacientes retirados del estudio CT P13 3.1 por cualquier motivo.
2. Pacientes que, en el momento de otorgar el consentimiento informado, tienen cualquier problema médico, como AAG o problemas de intolerancia que hagan que la continuación en el estudio pudiera ser perjudicial para su salud, en opinión del investigador.
3. El paciente tiene previsto participar en un estudio con un fármaco en investigación durante el período de este estudio de extensión.
4. Mujer que tiene previsto quedarse embarazada o dar el pecho durante el período del estudio.
5. Paciente que prevé recibir una vacuna viva o atenuada o que tiene cita para recibir una vacuna viva o atenuada durante el período del estudio. Las vacunas inactivadas son aceptables durante el estudio.
6. Pacientes que, en opinión de su médico de atención primaria o del investigador, no deben participar en este estudio de extensión por cualquier motivo.
7. Pacientes sometidos a alguna intervención quirúrgica, incluidas las de huesos o articulaciones o la sinoviectomía (incluida la fusión o sustitución de una articulación) durante las 12 semanas previas al momento de otorgar el consentimiento informado o que tengan previsto someterse a una intervención durante los 6 meses siguientes al momento de otorgar el consentimiento informado.
8. Paciente que, en el momento de otorgar el consentimiento informado, está tomando, tenga previsto tomar o deba tomar durante el estudio, cualquiera de los medicamentos concomitantes siguientes:
- Corticosteroides, salvo glucocorticoides orales, en una dosis diaria máxima equivalente a 10 mg de prednisolona. (El paciente podrá recibir preparados de glucocorticoides de baja potencia de aplicación tópica, ótica u oftálmica, siempre que se administren con arreglo a las instrucciones indicadas en la ficha técnica del producto.)
- Medicamentos antirreumáticos modificadores de la enfermedad distintos del metotrexato, como hidroxicloroquina, cloroquina, sulfasalazina o leflunomida.
- Alquilantes.
- Vacuna de microorganismos vivos o atenuados.
- Cualquier producto biológico para el tratamiento de la AR, salvo CT-P13 o Remicade.

E.5 End points

E.5.1

Primary end point(s)

Efficacy endpoint evaluations are:
- Individual components of the ACR criteria comparison with baseline of Study CT-P13 3.1 at Weeks 78 and 102 (or the End-of-Study Visit if not obtained at Week 102)
- Mean decrease in disease activity measured by DAS28 comparison with baseline of Study CT-P13 3.1 at Weeks 78 and 102 (or the End-of-Study Visit if not obtained at Week 102)
- Proportion of patients with a good response defined according to the EULAR response criteria at Weeks 78 and 102 (or the End-of-Study Visit if not obtained at Week 102)
- Proportion of patients achieving ACR20, ACR50, and ACR70 at Weeks 78 and 102 (or the End-of-Study Visit if not obtained at Week 102)
- Hybrid ACR response at Weeks 78 and 102 (or the End-of-Study Visit if not obtained at Week 102)
- Joint damage progression at Week 102 (or the End-of-Study Visit if not obtained at Week 102)
- Number of patients requiring salvage retreatment at Week 102 (or the End-of-Study Visit if not obtained at Week 102)

The safety endpoint evaluations are:
- Immunogenicity at Weeks 78 and 102 (or the End-of-Study Visit if not obtained at Week 102)
- Vital sign measurements
- ECG findings at Week 102 (or the End-of-Study Visit if not obtained at Week 102)
- Interferon-gamma release assay
- Physical examination findings
- Clinical laboratory tests including urine pregnancy, ESR, and CRP tests
- AEs including SAEs
- Concomitant medications
- Signs and symptoms of TB
- Infections
- Infusion-related reactions
- Malignancies

Los criterios de valoración de la eficacia son:
- Componentes individuales de la comparación de los criterios ACR con respecto al valor basal del estudio CT-P13 3.1 en las semanas 78 y 102 (o en la visita final del estudio si no se hizo en la semana 102).
- Disminución media de la actividad de la enfermedad mediante la comparación de DAS28 con respecto al valor basal del estudio CT-P13 3.1 en las semanas 78 y 102 (o en la visita final del estudio si no se hizo en la semana 102).
- Proporción de pacientes con buena respuesta definida por los criterios de respuesta EULAR en las semanas 78 y 102 (o en la visita final del estudio si no se hizo en la semana 102).
- Proporción de pacientes que alcanzan una respuesta ACR20, ACR50 y ACR70 en las semanas 78 y 102 (o en la visita final del estudio si no se hizo en la semana 102).
- Respuesta ACR híbrida en las semanas 78 y 102 (o en la visita final del estudio si no se hizo en la semana 102).
- Progresión del daño articular en la semana 102 (o en la visita final del estudio si no se hizo en la semana 102).
- Número de pacientes que necesitan repetir el tratamiento de rescate en la semana 102 (o en la visita final del estudio si no se hizo en la semana 102).

Las evaluaciones de los criterios de valoración de la seguridad son:
- Inmunogenicidad en las semanas 78 y 102 (o en la visita final del estudio si no se hizo en la semana 102).
- Mediciones de las constantes vitales.
- Resultados del ECG en la semana 102 (o en la visita final del estudio si no se hizo en la semana 102).
- Prueba de liberación del interferón gamma.
- Resultados de la exploración física.
- Análisis clínicos con prueba de embarazo en orina, VSG y PCR.
- AA, incluidos los AAG.
- Medicamentos concomitantes.
- Signos y síntomas de tuberculosis.
- Infecciones.
- Reacciones relacionadas con la infusión.
- Tumores malignos.

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy will be evaulated at: week 78, 102 and 110
Safety will be evaulated at: week 62, 70, 78, 86, 94, 102 and 110

La eficacia se evaluará en: semana 78, 102 y 110.
La seguridad se evaluará en: semana 62, 70, 78, 86, 94, 102 y 110

E.5.2

Secondary end point(s)

Not applicable

No aplica.

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

No aplica.

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

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

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)

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

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

Austria

Bosnia and Herzegovina

Bulgaria

Chile

Colombia

Italy

Jordan

Latvia

Lithuania

Mexico

Peru

Philippines

Poland

Portugal

Romania

Slovakia

Spain

Ukraine

United Kingdom

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 end of the study is defined as the date on which the last patient completes the last visit (includes End-of-Study Visit).

El final del estudio se define como la fecha en la que el último paciente completa la última visita (incluye la visita de final del estudio).

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