Clinical Trials Register

Summary
EudraCT Number:	2017-004369-29
Sponsor's Protocol Code Number:	206854
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:	2018-05-21
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

2017-004369-29

A.3

Full title of the trial

The Clinical Effectiveness of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in a Single Inhaler (TRELEGYTM ELLIPTATM) when Compared with Non-ELLIPTA Multiple Inhaler Triple Therapies in COPD Patients within a Usual Care Setting.

Short Title: INTREPID: INvestigation of TRELEGY Effectiveness: Usual PractIce
Design

Efectividad clínica de Furoato de Fluticasona/Bromuro de Umeclidinio /Vilanterol en un solo inhalador (TRELEGY® ELLIPTA®) en comparación con terapias triples en varios dispositivos no-ELLIPTA, en pacientes con EPOC en la práctica clínica habitual.

Título abreviado: INTREPID: INvestigation of TRELEGY Effectiveness: Usual PractIce Design (Investigación de la efectividad de TRELEGY: diseño según práctica habitual)

A.3.1

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

Single Inhaler Triple Therapy (fluticasone furoate + vilanterol trifenatate + umeclidinium bromide) (inhaled) - COPD

Triple terapia en un solo inhalador (Furoato de Fluticasona /Bromuro de Umeclidinio /Vilanterol) - EPOC

A.4.1

Sponsor's protocol code number

206854

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	GlaxoSmithKline, S.A.
B.1.3.4	Country	Spain
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	GSK
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline
B.5.2	Functional name of contact point	Centro de Información
B.5.3	Address:
B.5.3.1	Street Address	C/Severo Ochoa, 2 (P.T.M.)
B.5.3.2	Town/ city	Tres Cantos (Madrid)
B.5.3.3	Post code	28760
B.5.3.4	Country	Spain
B.5.4	Telephone number	34902202700
B.5.5	Fax number	34918070479
B.5.6	E-mail	es-ci@gsk.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	Yes
D.2.1.1.1	Trade name	Trelegy Ellipta
D.2.1.1.2	Name of the Marketing Authorisation holder	GSK Trading Services Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Fluticasone Furoate/Umeclidinium/Vilanterol
D.3.2	Product code	GW685698/GSK573719/GW642444
D.3.4	Pharmaceutical form	Inhalation powder, pre-dispensed
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUTICASONE FUROATE
D.3.9.1	CAS number	397864-44-7
D.3.9.2	Current sponsor code	GW685698
D.3.9.4	EV Substance Code	SUB26593
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Umeclidinium
D.3.9.1	CAS number	869113-09-7
D.3.9.2	Current sponsor code	GSK573719
D.3.9.3	Other descriptive name	GSK573719A
D.3.9.4	EV Substance Code	SUB31865
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	62.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Vilanterol Trifenatate
D.3.9.1	CAS number	503068-34-6
D.3.9.2	Current sponsor code	GW642444
D.3.9.3	Other descriptive name	GW642444M
D.3.9.4	EV Substance Code	SUB30696
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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

Chronic Obstructive Pulmonary Disease (COPD) which may be called emphysema or chronic bronchitis.

Enfermedad pulmonar obstructiva crónica (EPOC) que puede llamarse enfisema o bronquitis crónica.

E.1.1.1

Medical condition in easily understood language

Chronic Obstructive Pulmonary Disease (COPD) COPD is a condition that affects the lungs.

La Enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad que afecta a los pulmones.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

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	10010952
E.1.2	Term	COPD
E.1.2	System Organ Class	100000004855

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 compare the effectiveness of TRELEGY ELLIPTA with non-ELLIPTA MITT for the impact of COPD on wellbeing and daily life after 24 weeks’ treatment.

Comparar la eficacia de TRELEGY ELLIPTA con la de terapias triples en varios dispositivos (TTVD) no-ELLIPTA, en cuanto al efecto de la EPOC sobre el bienestar y la vida cotidiana, después de 24 semanas de tratamiento.

E.2.2

Secondary objectives of the trial

Secondary:
- To compare the effectiveness of TRELEGY ELLIPTA with non-ELLIPTA MITT on lung function after 24 weeks’ treatment.
- To compare critical errors (CE) made by study participants using the ELLIPTA device with participants using selected non- ELLIPTA MITT after 24 weeks’ treatment.
Other:
- To compare TRELEGY ELLIPTA with inhaled non-ELLIPTA MITT for a clinically important deterioration (CID)
-To quantify the incidence, rate and time to first moderate/severe COPD exacerbation for study participants on TRELEGY ELLIPTA compared with participants on non-ELLIPTA MITT.
-To compare the effectiveness of TRELEGY ELLIPTA with non-ELLIPTA MITT for COPD-related Healthcare Resource Utilisation (HCRU).
Exploratory:
-To assess the data for correlation between critical errors and clinical outcomes
-To describe the patient study experience
Safety:
-To compare safety for study participants using the ELLIPTA device with participants using non-ELLIPTA MITT after 24 weeks’ treatment.

Secundarios:
- Comparar la eficacia de TRELEGY ELLIPTA con la de TTVD no-ELLIPTA sobre la función respiratoria después de 24 sems de tto.
- Comparar los errores críticos (EC) cometidos por los participantes en el estudio que utilicen el inhalador ELLIPTA con los cometidos por los que utilicen TTVD no- ELLIPTA seleccionados después de 24 sems. de tto.
Otros:
- Comparar TRELEGY ELLIPTA con TTVD no- ELLIPTA inhalados en cuanto al DCI.
- Cuantificar la incidencia, la tasa y el tiempo transcurrido hasta la primera exacerbación moderada o grave de la EPOC en los participantes tratados con TRELEGY ELLIPTA en comparación con los tratados con TTVD no- ELLIPTA.
- Comparar la eficacia de TRELEGY ELLIPTA con la de TTVD no- LLIPTA en cuanto a la URS relacionados con la EPOC.
Exploratorios
- Evaluar los datos en busca de una correlación entre EC y criterios de valoración clínicos.
- Describir la experiencia del paciente en el estudio.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
1. Informed Consent: Capable of giving signed informed consent as described in Appendix 2 of study protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. COPD Diagnosis: Patients with a documented physician diagnosis of COPD.
3. Severity of COPD symptoms: A score of ≥10 on the COPD Assessment Test (CAT) at screening.
4. History of Exacerbations. Patients who have a history of treatment with systemic/oral corticosteroids, antibiotics and/or hospitalisation for at least one COPD exacerbation in the 3 years prior to randomisation. This will be captured through patient recall and/or medical records and must be documented in patients notes.
Prior use of systemic/oral corticosteroids and/or antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD.
5. Existing COPD Maintenance Treatment. Patients currently receiving one of the non-ELLIPTA maintenance therapies listed below who have been prescribed it continually for at least 16 weeks prior to randomisation.
Continuous prescription is defined as a minimum of 60 days’ prescription cover during the prior 16 weeks.
The non -ELLIPTA maintenance therapy must be one of the following
- ICS in combination with LAMA and LABA (MITT)
- LAMA and LABA used in combination as a dual therapy
- LABA and ICS used in combination as a dual therapy
NOTE: patients who are currently on a dual maintenance therapy for COPD must be considered by their physician to require a step- up to triple therapy. The reason for the physician decision to step- up must be documented.
Patients who are receiving only COPD medication on an ‘as required’ basis are not eligible.
6. Age and Sex: participants must be aged ≥ 40 years of age at the time of signing the informed consent.

1. Consentimiento informado: pacientes capaces de otorgar su consentimiento informado, firmado tal como se indica en el Apéndice 2, lo que incluye el cumplimiento de los requisitos y restricciones enumerados en el documento de consentimiento informado (DCI) y en este protocolo.
2. Diagnóstico de EPOC: pacientes con diagnóstico documentado de EPOC por un médico.
3. Intensidad de los síntomas de la EPOC: puntuación CAT (Prueba de evaluación de la EPOC) ≥ 10 en la selección.
4. Antecedentes de exacerbaciones: pacientes con antecedentes de tratamiento con corticoides sistémicos u orales, antibióticos u hospitalización por al menos una exacerbación de la EPOC, en los tres años previos a la aleatorización. Ello se obtendrá a partir del recuerdo de los pacientes o la historia clínica y deberá documentarse en los registros de los pacientes.
El uso previo de corticoides sistémicos u orales o antibióticos solamente, no se considera un antecedente de exacerbación a menos que el uso se haya asociado al tratamiento de un empeoramiento de los síntomas de la EPOC.
5. Tratamiento de mantenimiento existente de la EPOC: pacientes que estén recibiendo uno de los tratamientos de mantenimiento distintos de ELLIPTA enumerados a continuación y que les haya sido prescrito de manera continua durante al menos 16 semanas antes de la aleatorización.
La prescripción continua se define como una cobertura de prescripción de 60 días, como mínimo, durante las 16 semanas previas.
El tratamiento de mantenimiento distinto de ELLIPTA deberá ser uno de los siguientes:
- CI en combinación con LAMA y LABA (TTVD).
- LAMA y LABA utilizados en combinación como tratamiento doble.
- LABA y CI utilizados en combinación como tratamiento doble.
NOTA: En los pacientes que estén recibiendo un tratamiento de mantenimiento doble para la EPOC, el médico deberá valorar si precisan pasar a recibir un tratamiento triple. Deberá documentarse el motivo de la decisión del médico de pasar al tratamiento triple.
No podrán participar pacientes que estén recibiendo únicamente medicación para la EPOC ‘a demanda’.
6. Edad y sexo: El participante debe tener 40 años o más de edad en el momento de firmar el consentimiento informado.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
1. Women of child bearing potential. as defined in Appendix 4 of study protocol. This includes women who are pregnant or lactating or are planning on becoming pregnant during the study.
2. Medical Conditions: Patients with any life-threatening condition i.e. low probability, in the opinion of the investigator, of 6-month survival due to severity of COPD or comorbid condition.
3. Patients with unstable COPD. Patients with resolution of an exacerbation less than 2 weeks prior to visit 1, must not be randomised. Patients may be rescreened 2 weeks after resolution of exacerbation (exacerbation is defined by treatment with systemic corticosteroids and/or antibiotic).
4. Other diseases/abnormalities: patients with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the participant at risk through participation, or which would affect the effectiveness or safety analysis if the
disease/condition exacerbated during the study
5. Hypersensitivity: A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, β2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator
contraindicates study participation.
6. Prior/Concomitant Therapy with Oral Corticosteroid Patients who, in the opinion of the treating investigator, are chronic users of oral corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening).
Chronic use is defined as more than 14 days continuous use during the 12 weeks prior to visit 1.
7. Participants currently participating in any interventional clinical study.
Participants taking any investigational drug treatment within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study (whichever is the longer of the two).

1. Mujeres en edad fértil, según se define en el Apéndice 4. Entre ellas se incluyen las mujeres embarazadas o en período de lactancia o que tengan previsto quedarse embarazadas durante el estudio.
2. Enfermedades: Pacientes con cualquier enfermedad potencialmente mortal, es decir, con baja probabilidad, en opinión del investigador, de supervivencia a los seis meses debido a la gravedad de la EPOC o la enfermedad coexistente.
3. Pacientes con EPOC inestable. Los pacientes con resolución de una exacerbación menos de dos semanas antes de la visita 1, no podrán ser aleatorizados. Los pacientes podrán someterse de nuevo al proceso de selección dos semanas después de la resolución de la exacerbación (exacerbación definida como la necesidad de tratamiento con antibióticos y/o esteroides sistémicos u hospitalización).
4. Otras enfermedades o anomalías: Pacientes con antecedentes o datos presentes de enfermedad no controlada o de importancia clínica. ‘De importancia clínica’ se define como toda enfermedad que, en opinión del investigador, pondría en riesgo la seguridad del paciente al participar o que pueda afectar al análisis de la eficacia o la seguridad en caso de que empeore durante el estudio.
5. Hipersensibilidad: Antecedentes de alergia o hipersensibilidad a corticoides, anticolinérgicos o antagonistas de receptores muscarínicos, agonistas β2, lactosa/proteínas de la leche o estearato de magnesio o de un trastorno médico, como glaucoma de ángulo estrecho, hipertrofia prostática u obstrucción del cuello de la vejiga, que, en opinión del investigador, contraindiquen la participación en el estudio.
6. Tratamiento previo/concomitante con corticoides orales. Pacientes que, en opinión del investigador responsable del tratamiento, sean usuarios crónicos de corticoides orales para indicaciones respiratorias o de otro tipo (en caso de duda, deberá comentarse con el monitor médico antes de la selección).
El uso crónico se define como más de 14 días de uso continuo durante las 12 semanas previas a la visita 1.
7. Participantes que ya estén participando en algún estudio clínico intervencionista.
Participantes que hayan recibido cualquier fármaco en investigación en los 30 días previos a la visita 1 o en el período equivalente a cinco semividas (t½) del estudio de investigación previo (lo que suponga más tiempo).

E.5 End points

E.5.1

Primary end point(s)

Proportion of responders based on the COPD Assessment Test (CAT) at week 24. Response defined as change from baseline of CAT score ≥ 2 at 24 weeks.

Proporción de pacientes con respuesta según la puntuación CAT (Prueba de evaluación de la EPOC) en la semana 24. Respuesta definida como una variación con respecto al valor basal de la puntuación CAT ≥ 2, a las 24 semanas.

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks

24 semanas

E.5.2

Secondary end point(s)

1. Change from baseline in Forced Expiratory Volume in one second (FEV1) at 24 weeks (subgroup of patients).

2. Percentage of participants making at least 1 critical error in inhalation technique at the 24-week visit. (subgroup of patients).

1. Variación con respecto al valor basal del volumen espiratorio forzado en el primer segundo (FEV1) a las 24 semanas (subgrupo de participantes).
2. Porcentaje de participantes que cometan al menos un error crítico en la técnica de inhalación a las 24 semanas (subgrupo de participantes).

E.5.2.1

Timepoint(s) of evaluation of this end point

24 weeks

24 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

E.6.4

Safety

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

The primary purpose of this study is to meet this need by assessing the effectiveness of TRELEGY ELLIPTA relative to non-ELLIPTA MITT within the usual clinical practice setting

El objetivo principal de este estudio consiste en evaluar la eficacia de TRELEGY ELLIPTA en comparación con tratamientos triples con varios inhaladores (TTVI) distintos de ELLIPTA para controlar la enfermedad pulmonar obstructiva crónica (EPOC) en el contexto de la práctica clínica habitual.

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

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

Yes

E.8.1.7.1

Other trial design description

Effectiveness

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

147

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

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:

3000

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

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

300

F.4.2

For a multinational trial

F.4.2.1

In the EEA

3000

F.4.2.2

In the whole clinical trial

3000

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)

There is no plan to continue to provide study treatment following the end of the study. At the end of the study, the choice of COPD maintenance treatment is at the discretion and clinical judgment of the physician.

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

2018-08-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-10-10

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