Clinical Trials Register

Summary
EudraCT Number:	2016-004477-40
Sponsor's Protocol Code Number:	GLPG2222-CL-202
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:	2017-03-10
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

2016-004477-40

A.3

Full title of the trial

A Phase IIa, randomized, double-blind, placebo-controlled study to evaluate multiple doses of GLPG2222 in subjects with Cystic Fibrosis who are homozygous for the F508del mutation

Estudio en fase IIa, aleatorizado, doble ciego, controlado con placebo para evaluar varias dosis de GLPG2222 en sujetos con fibrosis quística que son homocigotos para la mutación F508del.

A.3.1

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

A study looking at the safety, tolerability and efficacy of the study drug GLPG2222 in patients with cystic fibrosis who have the F508del CFTR mutation on both alleles

Un estudio que estudia la seguridad, tolerabilidad y eficacia del fármaco del estudio GLPG2222 en pacientes con fibrosis quística que tienen la mutación CFTR F508del en ambos alelos

A.4.1

Sponsor's protocol code number

GLPG2222-CL-202

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	Galapagos NV
B.1.3.4	Country	Belgium
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	Galapagos NV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Galapagos NV
B.5.2	Functional name of contact point	Clinical trial information desk
B.5.3	Address:
B.5.3.1	Street Address	Generaal De Wittelaan L11 A3
B.5.3.2	Town/ city	Mechelen
B.5.3.3	Post code	2800
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+3493274 61 07
B.5.6	E-mail	rd@glpg.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	GLPG2222
D.3.2	Product code	G957389
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	G957389
D.3.9.3	Other descriptive name	GLPG2222
D.3.9.4	EV Substance Code	SUB180106
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	50
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	GLPG2222
D.3.2	Product code	G957389
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	G957389
D.3.9.3	Other descriptive name	GLPG2222
D.3.9.4	EV Substance Code	SUB180106
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: 3
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	GLPG2222
D.3.2	Product code	G957389
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
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	G957389
D.3.9.3	Other descriptive name	GLPG2222
D.3.9.4	EV Substance Code	SUB180106
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	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

Cystic Fibrosis

Fibrosis Quística

E.1.1.1

Medical condition in easily understood language

Mucoviscidosis

E.1.1.2

Therapeutic area

Body processes [G] - Genetic Phenomena [G05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	PT
E.1.2	Classification code	10011762
E.1.2	Term	Cystic fibrosis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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 evaluate the safety and tolerability of 4 different doses of GLPG2222 administered orally and q.d. for 29 days in adult subjects with CF who are homozygous for the F508del CFTR mutation.

Evaluar la seguridad y tolerabilidad de 4 dosis diferentes de GLPG2222 administradas por vía oral una vez al día (1 v/d) durante 29 días en sujetos adultos con FQ que son homocigóticos para la mutación del CFTR F508del.

E.2.2

Secondary objectives of the trial

To assess changes in biomarkers of CFTR activity.
To assess changes in respiratory symptoms.
To assess the pharmacokinetics (PK) of GLPG2222.

--Evaluar los cambios en los biomarcadores de la actividad del CFTR.
– Evaluar los cambios en los síntomas respiratorios.
– Evaluar la farmacocinética (FC) del GLPG2222.

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

Subjects have the option to participate in a sub-study, in which nasal brushings will be collected. Nasal brushings will be obtained at the time points specified in the protocol and only from those subjects who give separate consent for this optional sub-study.

Los sujetos pueden optar por participar en el subestudio opcional, en el que se recogerán cepillados nasales.Los cepillados nasales se obtendrán en los puntos temporales especificados en el diagrama de flujo y solo de los sujetos que den su consentimiento aparte para este subestudio opcional.

E.3

Principal inclusion criteria

• Male or female subject ≥ 18 years of age on the day of signing the ICF.
• A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation (documented in the subject’s medical record or CF registry).
• Weight ≥ 40 kg during the screening period.
• Stable concomitant medication regimen for at least 4 weeks prior to the first study drug administration and continuing the same regimen for the duration of the study.
• FEV1 ≥ 40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).

·Hombre o mujer de edad ≥18 años el día de la firma del FCI.
·Un diagnóstico clínico confirmado de FQ y homocigoto para la mutación del CFTR F508del (documentada en la historia médica del sujeto o en el registro de la FQ).
·Peso ≥40 kg durante el período de selección.
·Una pauta de medicación concomitante estable durante al menos 4 semanas antes de la primera administración del fármaco del estudio y continuar la misma pauta durante todo el estudio.
·VEF1 ≥40 % del valor normal predicho para la edad, el sexo y la estatura en la selección (antes o después del broncodilatador).

E.4

Principal exclusion criteria

• History of clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator.
• Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks prior to the first study drug administration.
• Need for supplemental oxygen during the day, and > 2 L/minute while sleeping.
• History of hepatic cirrhosis with portal hypertension (e.g. signs/symptoms of splenomegaly, esophageal varices, etc.).
• Concomitant use of any strong inhibitor(s) or inducer(s) of CYP3A4 within 4 weeks prior to the first study drug administration.
• Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration.
• Concomitant use of CYP2C8 substrates within 4 weeks prior the first study drug administration.
• Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or ALT and/or alkaline phosphatase and/or gamma-glutamyl transferase (GGT) ≥ 3 x the upper limit of normal (ULN); and/or total bilirubin ≥ 1.5 x the ULN.
• Estimated creatinine clearance < 60 mL/minute using Cockcroft-Gault equation at screening.

• Antecedentes de enfermedad crónica clínicamente significativa inestable o incontrolada que haga que el sujeto no sea adecuado para su inclusión en el estudio en opinión del investigador.
• Estado pulmonar inestable o infección de las vías respiratorias (incluyendo rinosinusitis) que requiera un cambio de tratamiento durante las 4 semanas anteriores a la primera administración del fármaco del estudio.
• Necesidad de oxígeno suplementario durante el día y >2 l/min durante el sueño.
• Antecedentes de cirrosis hepática con hipertensión portal (p. ej., signos/síntomas de esplenomegalia, varices esofágicas, etc.).
• Uso concomitante de cualquier inhibidor o inductor potente del citocromo P450 (CYP)3A4 dentro de las 4 semanas anteriores a la primera administración del fármaco del estudio.
• Uso de tratamiento modulador del CFTR dentro de las 4 semanas anteriores a la primera administración del fármaco del estudio.
• Uso concomitante de sustratos de CYP2C8 dentro de las 4 semanas anteriores a la primera administración del fármaco del estudio.

• Prueba de la función hepática anómala en la selección, definida como aspartato aminotransferasa o alanina aminotransferasa y o fosfatasa alcalina o γ-glutamil-transferasa ≥3 x el límite superior de la normalidad (LSN) o bilirrubina total ≥1,5 x el LSN.
• Estimación del aclaramiento de creatinina <60 ml/min usando la ecuación de Cockcroft-Gault en la selección.

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability, assessed by the incidence of adverse events (AEs), as well as changes over time in weight, vital signs, oxygen saturation by pulse oximetry, 12-lead ECG, spirometry, and clinical safety laboratory data

Seguridad y tolerabilidad, evaluadas mediante la incidencia de acontecimientos adversos (AA), así como los cambios a lo largo del tiempo de peso, constantes vitales, saturación de oxígeno por oximetría de pulso, electrocardiograma (ECG) de 12 derivaciones, espirometría,y datos analíticos de seguridad clínica

E.5.1.1

Timepoint(s) of evaluation of this end point

Various time points throughout the trial as specified in the protocol

Varios tiempos a lo largo del Ensayo como se sespecifica en el Protocolo

E.5.2

Secondary end point(s)

• Change from baseline in sweat chloride concentration
• Change from baseline in percent predicted FEV1
• Change from baseline in the respiratory domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
• PK parameters of GLPG2222

-Cambio desde el momento inicial de la concentración de cloruro en el sudor
-Cambio desde el inicio en el porcentaje estimado de VEF1
-Cambio desde el inicio en la puntuación del dominio respiratorio del cuestionario revisado para la fibrosis quística(CFQ-R)
-Parámetros FC del GLPG2222.

E.5.2.1

Timepoint(s) of evaluation of this end point

• Sweat chloride concentration, percent predicted FEV1 and the respiratory domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at day 29
• PK parameters of GLPG2222 at various time points throughout the trial as specified in the protocol

·Concentración de cloruro,porcentaje estimado de VEF1 y del dominio respiratorio del cuestionario revisado para la fibrosis quística(CFQ-R) al día 29.
·Parámetros FC del GLPG2222 a Varios tiempos a lo largo del Ensayo como se sespecifica en el Protocolo

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Belgium

Netherlands

Serbia

Spain

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

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

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

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, treatment will revert to the standard of care

Ninguno, el tratamiento revertirá al cuidado estándar

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	ECFS - Clinical Trials Network
G.4.3.4	Network Country	Belgium
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	CFFT Therapeutics Development Network
G.4.3.4	Network Country	United States

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-05-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-03-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-10-19

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