Clinical Trials Register

Summary
EudraCT Number:	2017-003228-54
Sponsor's Protocol Code Number:	PBF-677-3
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:	2018-04-09
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

2017-003228-54

A.3

Full title of the trial

A Phase IIa (proof of concept), randomized, double blind, placebo controlled, multicenter clinical trial to evaluate the safety and efficacy of oral treatment with PBF-677 in patients with mild to moderate ulcerative colitis.

Ensayo clínico multicéntrico de fase IIa (prueba de concepto) aleatorizado, con doble enmascaramiento y controlado con placebo para evaluar la seguridad y eficacia del tratamiento oral con PBF-677 en pacientes con colitis ulcerosa de leve a moderada.

A.3.1

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

A clinical trial to evaluate the safety and efficacy of oral treatment with PBF-677 in patients with mild to moderate ulcerative colitis.

Ensayo clínico para evaluar la seguridad y eficacia del tratamiento oral con PBF-677 en pacientes con colitis ulcerosa de leve a moderada.

A.4.1

Sponsor's protocol code number

PBF-677-3

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	PaloBiofarma S.L.
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	PaloBiofarma S.L.
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	QualitecFarma s.l.
B.5.2	Functional name of contact point	Óscar Mesa del Castillo
B.5.3	Address:
B.5.3.1	Street Address	Musgo 2, Edificio Europa II, 2ª planta. Oficina H
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28023
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3491372 83 99 / 84 00
B.5.6	E-mail	clinical.trials@qualitecfarma.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.3.2	Product code	PBF-677
D.3.4	Pharmaceutical form	Capsule, hard
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	PBF-677
D.3.9.2	Current sponsor code	PBF-677
D.3.9.4	EV Substance Code	SUB178868
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	200
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	Capsule, hard
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

Inflammatory Bowel disease, mild to moderate Ulcerative Colitis

Enfermedad Inflamatoria Intestinal, Colitis Ulcerosa de leve a moderada

E.1.1.1

Medical condition in easily understood language

Inflammatory Bowel disease, mild to moderate Ulcerative Colitis

Enfermedad Inflamatoria Intestinal, Colitis Ulcerosa de leve a moderada

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

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 trial primary goal will be to evaluate the safety and tolerability of PBF-677 in patients with mild to moderate active ulcerative colitis disease over 28 days.

El objetivo principal del ensayo será evaluar la seguridad y la tolerabilidad de PBF-677 en pacientes con colitis ulcerosa activa de leve a moderada durante 28 días.

E.2.2

Secondary objectives of the trial

The trial also will explore pharmacokinetics (PK) profile and preliminary therapeutic efficacy associated with PBF-677 through biomarker analysis and clinical assessments

El ensayo también investigará el perfil farmacocinético (PK) y la eficacia terapéutica preliminar del PBF-677 a través del análisis de biomarcadores y evaluaciones clínicas.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must meet the following criteria for study entry:
- Able and willing to provide written informed consent
- Male or Female, 18 to 75 years of age, inclusive
- Patient with previous diagnosis of ulcerative colitis (extensive or pancolitis, E3 of Montreal Classification) established at least 3 months prior to screening and determined by ordinary clinical, endoscopic, and histological procedures.
- Patient who has stable oral 5-ASA dose ≤ 3 gr/day treatment, within 1 month prior to screening.
- Mild-to-moderate activity of the disease determined clinically during the screening period by Partial Mayo Clinical Score of ≤ 6, with rectal bleeding score ≤ 2 and/or a bowel frequency score ≤ 2.
- Patient in flare of the disease.
- Patient with faecal calprotectin levels > 50 mg/Kg
- Availability for the entire study period, absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; willingness to adhere to the protocol requirements, ability to cooperate adequately, to understand and follow the instructions of the physician or designee.
- Women who are not postmenopausal (at least 12 months) or surgically sterile must have a negative pregnancy test at screening and at the end of study and either abstain from sexual intercourse or use a highly effective method of birth control for the duration of the study and after 12 weeks after the last dose of study drug.
- For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm for the duration of the study and after 12 weeks from the last dose of study drug.

Los pacientes deben cumplir los criterios siguientes para entrar en el estudio:
• Tener capacidad y voluntad de dar su consentimiento informado por escrito
• Hombres o mujeres de 18 a 75 años de edad, inclusive
• Paciente con diagnóstico previo de colitis ulcerosa extensa o pancolitis, E3 de la clasificación de Montreal establecida al menos 3 meses antes de la selección y determinada por procedimientos clínicos, endoscópicos e histológicos ordinarios.
• Pacientes en tratamiento con dosis orales estables de 5-ASA ≤ 3 g/día, en el mes previo a la selección.
• Pacientes con colitis ulcerosa activa de leve a moderada determinada clínicamente durante el periodo de selección mediante el índice parcial de la Clínica Mayo de ≤ 6, con un índice de hemorragias rectales ≤ 2 o un índice de la frecuencia de las deposiciones ≤ 2.
• Pacientes con niveles de calprotectina fecal > 50 mg/Kg
• Pacientes que presenten un brote de la enfermedad.
• Disponibilidad durante todo el período de estudio, ausencia de problemas intelectuales que puedan limitar la validez del consentimiento para participar en el estudio o el cumplimiento de los requisitos del protocolo, voluntad de cumplir los requisitos del protocolo, capacidad para colaborar adecuadamente, comprender y seguir las instrucciones del médico o su representante.
• Las mujeres no posmenopáusicas (al menos 12 meses) o quirúrgicamente esterilizadas deben presentar una prueba de embarazo negativa en la selección y al final del estudio y abstenerse de mantener relaciones sexuales o utilizar un método anticonceptivo muy eficaz durante todo el estudio y en las 12 semanas siguientes a la última dosis del fármaco del estudio.
• Para los hombres: acuerdo de abstinencia sexual o uso de métodos anticonceptivos y de no donar esperma durante todo el estudio y en las 12 semanas siguientes a la última dosis del fármaco del estudio.

E.4

Principal exclusion criteria

Patients must not meet any of the following criteria for study entry:
- Patient who has treatment, within 3 months prior to screening, with immunomodulators including corticosteroids, azatioprine, mercaptopurine, biologics, tacrolimus, cyclosporine, for disease control.
- Patient who has stable oral 5-ASA dose > 3 gr/day treatment, within 1 month prior to screening.
- Patient with C-reactive Protein levels (CRP) ≥ 10 mg/L
- Patient who has topic 5-ASA treatment, within 1 month prior to screening.
- Patient who has anti-diarrheal treatment, within 3 months prior to screening.
- Use of prescription medications started or with a dose adjustment within 4 weeks prior to study enrolment, or OTC medications or supplements started or with a dose adjustment within 2 weeks prior study enrolment.
- Use of products, food supplements or medical devices, whose composition includes probiotics in the 3 months prior to the selection.
- Patient who has fulminant or severe colitis, toxic megacolon, primary sclerosing cholangitis, Crohn's disease, history of colitis associated colonic dysplasia or active peptic ulcer disease.
- Patient who has prior extensive colonic resection, subtotal or total colectomy or planned surgery for UC
- Patient who has past or present fistula or abdominal abscess
- Patient who has clinically significant diseases and/or infections captured in the medical history or evidence of clinically significant findings on physical examination and/or clinically significant ordinary laboratory evaluations (haematology, biochemistry, and urinalysis) or ECG.
- Patient who has evidence of significant liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
- Patient who is currently participating in another clinical trial of an investigational drug or medical device within 90 days prior to screening.
- Patient who is pregnant or lactating
- Inability to comply with study protocol, in opinion of the investigator
- History of alcohol, drug or chemical abuse within 6 months prior to screening
- History of cancer except local basal or squamous cell carcinoma of the skin that has been excised and is considered cured.

• Pacientes en tratamiento en los 3 meses previos a la selección con inmunomoduladores, como corticoesteroides, azatioprina, mercaptopurina, productos biológicos, tacrolimus, ciclosporina, para el control de la enfermedad.
• Pacientes en tratamiento con dosis oral de 5-ASA > 3g/día , en el mes previo a la selección.
• Pacientes con niveles de Proteína C-reactiva (PCR) ≥ 10 mg/L.
• Pacientes en tratamiento tópico con 5-ASA, en el mes previo a la selección.
• Pacientes en tratamiento con antidiarreicos en los 3 meses previos a la selección.
• Uso de medicamentos con receta iniciados o con dosis ajustada en las 4 semanas previas a la inclusión en el estudio o medicaciones sin receta o suplementos iniciados o con ajuste de dosis en las 2 semanas anteriores a la inclusión en el estudio.
• Pacientes con colitis fulminante o grave, megacolon tóxico, colangitis esclerosante primaria, enfermedad de Crohn, antecedentes de colitis relacionada con displasia de colon o ulcera péptica activa.
• Pacientes con resección extensa previa del colon, colectomía subtotal o total o cirugía programada para la CU.
• Pacientes con fístula previa o actual o absceso abdominal.
• Pacientes con enfermedades o infecciones clínicamente significativas recogidas en los antecedentes médicos o evidencia de observaciones clínicamente significativas en la exploración clínica o evaluaciones analíticas habituales importantes (hematología, bioquímica y análisis de orina) o ECG.
• Pacientes con evidencia de enfermedad hepática o renal importante o cualquier otra patología que interfiera en la absorción, distribución, metabolismo o excreción de fármacos o que se sepa que potencia o predispone a efectos no deseados.
• Pacientes que están participando actualmente en otro ensayo clínico con un fármaco o un producto médico en fase de investigación en los 90 días previos a la selección.
• Pacientes embarazadas o en período de lactancia.
• Incapacidad para cumplir el protocolo del estudio, en opinión del investigador.
• Antecedentes de abuso de alcohol, drogas o sustancias químicas en los 6 meses previos a la selección.
• Antecedentes de cáncer, excepto carcinoma basocelular o escamocelular localizado que se haya extirpado y se considere curado.
• Uso de productos, complementos alimenticios o dispositivos médicos, en cuya composición se incluyan probióticos en los 3 meses previos a la selección.

E.5 End points

E.5.1

Primary end point(s)

Safety Assessments
- Safety of PBF-677 administered for 28 days by assessing the number, severity, and type of AE, including changes in vital signs, physical examination, safety laboratory values, and ECGs.

Efficacy Assessments:
- Effect of PBF-677 on Faecal calprotectin levels [ Time Frame: Day 1, Day 7, Day 14, Day 21 and Day 28]
- Change in Partial Mayo Clinical Score induced by PBF-677 treatment compared to placebo [ Time Frame: Day 1, Day 14 and Day 28]

Evaluaciones de seguridad
- Seguridad de PBF-677 administrado durante 28 días evaluando el número, gravedad y tipo de AA, incluidos los cambios en las constantes vitales, exploración clínica, valores analíticos de seguridad y ECG.

Evaluaciones de eficacia
- Efecto de PBF-677 en los niveles de calprotectina fecal [Fechas: Día 1, Día 7, Día 14, Día 21 y Día 28]
- Cambio en el índice parcial de la Clínica Mayo inducido por el tratamiento con PBF-677 en comparación con placebo [Fechas: Día 1, DÍA 14 y Día 28]

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety Assessments
- Safety of PBF-677 administered for 28 days by assessing the number, severity, and type of AE, including changes in vital signs, physical examination, safety laboratory values, and ECGs.

Efficacy Assessments
- Effect of PBF-677 on Faecal calprotectin levels [ Time Frame: Day 1, Day 7, Day 14, Day 21 and Day 28]
- Change in Partial Mayo Clinical Score induced by PBF-677 treatment compared to placebo [ Time Frame: Day 1, Day 14 and Day 28]

E.5.2

Secondary end point(s)

Pharmacokinetics
- Pharmacokinetics (PK): Cmax in plasma (Time Frame: Day 1 and Day 14; Tmax in plasma [ Time Frame: Day 1 and Day 14]; Area under curve (AUC) in plasma [ Time Frame: Day 1 and Day 14]; Ctrough in plasma [ Time Frame: Day 1 and Day 14];

Farmacocinética
- Farmacocinética (FC): Cmáx en plasma (Fechas: Día 1 y Día 14; Tmáx en plasma [Fechas: Día 1 y Día 14; Área bajo la curva (AUC) en plasma [Fechas: Día 1 y Día 14; Tmáx en plasma [Fechas: Día 1 y Día 14];

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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

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

Ultima 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

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

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.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)

Principal Investigator decission

A criterio del investigador principal

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

2018-05-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-04-09

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

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