Clinical Trials Register

Summary
EudraCT Number:	2015-002900-10
Sponsor's Protocol Code Number:	APD001
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-04-27
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

France - ANSM

A.2

EudraCT number

2015-002900-10

A.3

Full title of the trial

AN OPEN-LABEL EXPLORATORY STUDY OF UCB5857 IN SUBJECTS WITH ACTIVATED PHOSPHOINOSITIDE 3 KINASE (PI3K) DELTA SYNDROME (APDS)

ÉTUDE EXPLORATOIRE OUVERTE ÉVALUANT L’UCB5857 CHEZ DES PATIENTS PRÉSENTANT UN SYNDROME DE PHOSPHO-INOSITIDE-3-KINASE (PI3K) DELTA ACTIVÉE (SYNDROME APDS)

A.3.1

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

Study of UCB5857 in subjects with APDS.

Étude évaluant l´UCB5857 chez des patients présentant un sydrome APDS.

A.4.1

Sponsor's protocol code number

APD001

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	UCB Celltech, UK Registered Branch of UCB Pharma SA
B.1.3.4	Country	United Kingdom
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	UCB Celltech
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	UCB BIOSCIENCES GmbH
B.5.2	Functional name of contact point	Clin Trial Reg & Results Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Alfred-Nobel-Strasse 10
B.5.3.2	Town/ city	Monheim
B.5.3.3	Post code	40789
B.5.3.4	Country	Germany
B.5.4	Telephone number	+492173481515
B.5.5	Fax number	+492173481573
B.5.6	E-mail	clinicaltrials@ucb.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	UCB5857
D.3.2	Product code	UCB5857
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	UCB5857
D.3.9.1	CAS number	1362850-20-1
D.3.9.2	Current sponsor code	UCB5857
D.3.9.4	EV Substance Code	SUB122669
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	5
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	UCB5857
D.3.2	Product code	UCB5857
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	UCB5857
D.3.9.1	CAS number	1362850-20-1
D.3.9.2	Current sponsor code	UCB5857
D.3.9.4	EV Substance Code	SUB122669
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	15
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	UCB5857
D.3.2	Product code	UCB5857
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	UCB5857
D.3.9.1	CAS number	1362850-20-1
D.3.9.2	Current sponsor code	UCB5857
D.3.9.4	EV Substance Code	SUB122669
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	30
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

Activated PI3K delta Syndrome (APDS)

Syndrome de PI3K delta activée (syndrome APDS)

E.1.1.1

Medical condition in easily understood language

Activated PI3K delta Syndrome (APDS)

Syndrome de PI3K delta activée (syndrome APDS)

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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

The primary objective is to evaluate the safety and tolerability of UCB5857 in subjects with Activated phosphoinositide-3 kinase (PI3K) delta Syndrome (APDS).

L’objectif principal est d’évaluer la tolérance et la sécurité d’emploi de l’UCB5857 chez des patients présentant un syndrome APDS.

E.2.2

Secondary objectives of the trial

The secondary objective is to assess the pharmacokinetic (PK) profile of UCB5857 in subjects with Activated phosphoinositide-3 kinase (PI3K) delta Syndrome (APDS).

L’objectif secondaire est d’évaluer le profil pharmacocinétique (PK) de l’UCB5857 chez des patients présentant un syndrome APDS.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Subject/legal representative is considered reliable and capable of adhering to the protocol (e.g. able to understand and complete diaries), visit schedule, or medication intake.

- Subject must have a confirmed genotypic diagnosis of APDS (i.e. proven pathogenic mutation in either the PIK3R1 or PIK3CD gene).

- Subjects must have had clinical findings and manifestations compatible with APDS such as nodal and/or extranodal lymphoproliferation, history of repeated oto-sinopulmonary infections and/or organ dysfunction (e.g., lung, liver)

- Le patient/représentant légal est considéré comme fiable et capable de respecter le protocole (par exemple, a la capacité de comprendre et de remplir les carnets journaliers), le calendrier des visites ou à la prise du médicament.

- Le patient doit avoir un diagnostic génotypique confirmé de syndrome APDS (c’est-à-dire une mutation pathogène avérée dans le gène PIK3R1 ou PIK3CD).

- Les patients doivent avoir eu des anomalies et manifestations cliniques compatibles avec un syndrome APDS, telles qu’une lymphoprolifération ganglionnaire et/ou extraganglionnaire, des antécédents d’infections oto-sino-pulmonaires répétées et/ou un dysfonctionnement d’un organe (par exemple, poumon, foie).

E.4

Principal exclusion criteria

1. Subject has participated in another study of an investigational medicinal product (IMP) (or a medical device) within the previous 30 days or is currently participating in another study of an IMP (or a medical device).
2. Subject has a history of allogeneic bone marrow transplantation.
3. Subject has no history of any clinical manifestations in last 12 months.
4. Subject tests positive for human immunodeficiency virus Type 1 or Type 2, hepatitis B surface antigen, or hepatitis C virus antibody.
5. Subject whose only clinical manifestations in the last 12 months are due to advanced bronchiectasis (declining lung function, 3 or more recurrent exacerbations, lung abscess, pneumothorax for repeating cough).
6. Subject who has a severe (life-threatening) infection during the screening period.
7. Subject who have lymphoma at the time of the screening or have been treated for lymphoma in the previous 5 years prior Screening (Visit 1).
8. Subject is female and is breast-feeding, pregnant, or plans to become pregnant or to start breastfeeding during the study or within 3 months following last dose of IMP.
9. Subject has WBC<2000/mm3, or absolute neutrophil count <1000/mm3 at Screening (Visit 1).
10. Subject has a history of chronic alcohol or drug abuse within the previous 6 months.
11. Subject has any relevant medical or psychiatric condition that could jeopardize or would compromise the subject’s ability to participate in this study.
12. Subject has a known hypersensitivity to any components of the IMP or comparative drugs as stated in this protocol.
13. Subject has been treated with any mTOR inhibitors (unless washed out, approximately 6 weeks).
14. Subject has a history of inflammatory bowel disease, peptic ulcers, or recurrent colitis including rectal bleeding (within 1 year prior to Screening [Visit 1]).
15. Subject has a body weight of less than 20 kg at Screening (Visit 1).

1. Participation à une autre étude évaluant un médicament expérimental (ME) (ou un dispositif médical) au cours des 30 jours précédents ou participe actuellement à une autre étude évaluant un ME (ou un dispositif médical).
2. Antécédents de greffe allogénique de moelle osseuse.
3. Absence d’antécédents de manifestations cliniques au cours des 12 derniers mois.
4. Résultats positifs aux tests de dépistage du virus de l’immunodéficience humaine de type 1 ou de type 2, de l’antigène de surface du virus de l’hépatite B ou des anticorps dirigés contre le virus de l’hépatite C.
5. Uniques manifestations cliniques au cours des 12 derniers mois dues à une bronchiectasie avancée (diminution de la fonction pulmonaire, 3 exacerbations récurrentes ou plus, abcès pulmonaire, pneumothorax pour toux répétée).
6. Infection sévère (pouvant mettre en jeu le pronostic vital) au cours de la période de sélection.
7. Présence d’un lymphome au moment de la sélection ou traitement pour un lymphome dans les 5 ans précédant la Sélection (Visite 1).
8. Allaitement ou grossesse en cours ou prévu(e) pendant l’étude dans les 3 mois suivant la dernière administration du ME.
9. Numération des globules blancs < 2 000/mm3 ou numération absolue des polynucléaires neutrophiles < 1 000/mm3 lors de la Sélection (Visite 1).
10. Antécédents de consommation chronique d’alcool ou de toxicomanie au cours des 6 mois précédents.
11. Pathologie médicale ou psychiatrique significative, susceptible de mettre en péril ou compromettre sa capacité à participer à cette étude.
12. Hypersensibilité connue à l’un des composants du ME ou aux médicaments comparatifs indiqués dans ce protocole.
13. Traitement antérieur par un inhibiteur de mTOR (sauf après une période de sevrage d’environ 6 semaines).
14. Antécédents de maladie inflammatoire de l’intestin, ulcères gastro-duodénaux ou colite récurrente, y compris saignement rectal (dans l’année précédent la Sélection [Visite 1]).
15. Le poids du patient est inférieur à 20 kg lors de la Sélection (Visite 1).

E.5 End points

E.5.1

Primary end point(s)

Safety variables
The safety variables will include:
• Incidence of AEs
• Incidence of SAEs
• Changes from Baseline in safety laboratory tests (serum chemistry, haematology, and urinalysis) at the time points measured
• Change from Baseline in vital sign parameters (systolic and diastolic blood pressure, temperature, pulse rate and respiratory rate) and body weight at the time points measured
• Change from Baseline in ECG parameters at the time points measured
• Physical examination findings.

Pharmacokinetic variable
The PK variable will be the plasma concentration of UCB5857.

Variables de sécurité d’emploi
Les variables de sécurité d’emploi inclueront:
• Incidence des évènements indésirables (EI)
• Incidence des évènements indésirables graves (EIG)
• Variation par rapport aux analyses biologiques de tolérance (biochimie sanguine, hématologie et analyse d’urine) en cours d´étude
• Variation par rapport aux paramètres de signes vitaux (pression artérielle systolique et diastolique, température, pouls et fréquence respiratoire) et du poids en cours d´étude
• Variation par rapport aux paramètres de l´ECG en cours d´étude
• Anomalies des examens cliniques.

Variable pharmacocinétique
La variable PK sera la concentration plasmatique de l’UCB5857.

E.5.1.1

Timepoint(s) of evaluation of this end point

At the time points measured.

E.5.2

Secondary end point(s)

Please refer to the study variables of the Clinical Trial Protocol.

Se référer aux variables étudiées du protocole de l´essai clinique

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to the study variables of the Clinical Trial Protocol.

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

A phase 1b study to evaluate the safety and tolerability of UCB5857 in subjects with APDS

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

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)

E.8.2.2

Placebo

E.8.2.3

Other

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

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

The end of the study is defined as the date of the last visit (or follow-up telephone call) of the last subject in the study.

La fin de l´étude est définie comme la date de la dernière visite (ou appel téléphonique de suivi) du dernier patient dans l´étude.

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

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)

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.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)

Subjects who complete the treatment period per protocol, and benefit from UCB5857 may have the option to receive UCB5857, as part of an open-label extension study, contingent on receipt of all required ethics and regulatory approvals.

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

2016-04-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-15

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
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