Clinical Trials Register

Summary
EudraCT Number:	2017-001695-26
Sponsor's Protocol Code Number:	FARM1275JK
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-04
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-001695-26

A.3

Full title of the trial

Monitoring the effectiveness and safety of biological drugs for treatment of psoriasis through evaluation of clinical and biological markers

Monitoraggio dell'efficacia e sicurezza di farmaci biologici nel trattamento della psoriasi: valutazione clinica e biomolecolare

A.3.1

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

Effectiveness and safety of biological drugs in psoriasis

Efficacia e sicurezza dei farmaci biologici nella psoriasi

A.3.2

Name or abbreviated title of the trial where available

FARM1275JK

A.4.1

Sponsor's protocol code number

FARM1275JK

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	ISTITUTI FISIOTERAPICI OSPITALIERI
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AIFA - Italian Medicines Agency
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Istituti Fisioterapici Ospitalieri
B.5.2	Functional name of contact point	Claudio Bonifati
B.5.3	Address:
B.5.3.1	Street Address	via E. Chianesi 53
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00144
B.5.3.4	Country	Italy
B.5.4	Telephone number	52665140
B.5.5	Fax number	52665166
B.5.6	E-mail	claudio.bonifati@ifo.gov.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Etanercept
D.3.2	Product code	[xxxx]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	185243-69-0
D.3.9.2	Current sponsor code	xxxx
D.3.9.3	Other descriptive name	Etanercept
D.3.10	Strength
D.3.10.1	Concentration unit	1X 100 milligrams/millilitre
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	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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	Yes
D.2.1.1.1	Trade name	STELARA - 45 MG - SOLUZIONE INIETTABILE IN SIRINGHE PRERIEMPITE - USO SOTTOCUTANEO - SIRINGA PRERIEMPITA(VETRO) O,5 ML(90MG/ML) 1 SIRINGA PRERIEMPITA DA 0.5ML
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Ustekinumab
D.3.2	Product code	[xxxx]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	815610-63-0
D.3.9.2	Current sponsor code	xxx
D.3.9.3	Other descriptive name	Ustekinumab
D.3.10	Strength
D.3.10.1	Concentration unit	1X 100 milligrams/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	45
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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	Yes
D.2.1.1.1	Trade name	STELARA - 90 MG - SOLUZIONE INIETTABILE IN SIRINGHE PRERIEMPITE - USO SOTTOCUTANEO - SIRINGA PRERIEMPITA(VETRO) 1 ML(90MG/ML) 1 SIRINGA PRERIEMPITA DA 1 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	ustekinumab
D.3.2	Product code	[xxxx]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	815610-63-0
D.3.9.2	Current sponsor code	xxxx
D.3.9.3	Other descriptive name	Ustekinumab
D.3.10	Strength
D.3.10.1	Concentration unit	1X 100 milligrams/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	90
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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

Moderate to severe psoriasis and joint disease

Psoriasi volgare da moderata a severa e artrite psoriasica

E.1.1.1

Medical condition in easily understood language

diffuse psoriasis

psoriasi volgare diffusa

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10037153
E.1.2	Term	Psoriasis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10037160
E.1.2	Term	Psoriatic arthritis
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• Primary objectives of the study will be to comparatively assess the effectiveness of anti-TNF-alfa (etanercept) and anti-p40 subunit of IL-12 and IL-23 (ustekinumab) on psoriasis patients with cutaneous and joint involvement.
The choice of etanercept among anti-TNF drugs is motivated by the following reasons: i) minor risk of infections (Altomare G et al. 2008); ii) equivalent therapeutic effect as compared to other anti-TNF drugs (Gladman DD. 2008) (27,28,29); ììì) opportunity to assess the efficacy of a biosimilar drug and the feasibility of its use in place of the “originator” with consequent reduction of the financial burden for the public health system (Aladul Mi et al. 2017).

Valutare la possibile differenza di efficacia di etanercept (anti-TNF) verso ustekinumab (anti IL12/23) nel trattamento della psoriasi con interessamento sia articolare che cutaneo (malattia psoriasica) rispetto a T0 nei tempi considerati (settimane 12, 24, 48, 72)

E.2.2

Secondary objectives of the trial

Secondary objectives of the study will be: 1) to assess the possible modifications of a series of soluble and cellular biomarkers involved in the pathogenesis of psoriatic disease after 12, 24 and 48 weeks of treatment; 2) evaluate the proportion of patients in the 2 treatment arms that maintains a state of MDA at weeks 24, 48, 72; 3) Safety assessment, through the registration of the number and type of emerging adverse events, with particular reference to those possibly or certainly related to the drugs administration.

1) Valutare le possibili modificazioni rispetto a T0 di una serie di marcatori cellulari e bioumorali implicati nell’immunopatogenesi della malattia psoriasica dopo 12, 24, 48 settimane di trattamento.
2) valutare la proporzione di pazienti nei 2 bracci di trattamento che mantiene uno stato di MDA nelle tempistiche successive alla settimana 12 (settimane: 24, 48, 72)
3) La sicurezza sarà valutata attraverso la registrazione della numerosità e tipologia degli eventi avversi, con particolare riferimento a quelli riconducibili alle terapie somministrate
La sicurezza sarà valutata attraverso la registrazione della numerosità e tipologia degli eventi avversi, con particolare riferimento a quelli riconducibili alle terapie somministrate

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

both sexes, aged 18-75, affected by moderate to severe psoriasis eligible to systemic treatment with biologic drugs (etanercept, stelara), either as first line therapy or after three months of wash out will be enrolled in the study.

Entrambi i sessi, età compresa fra 18 e 75 anni, affetti da psoriasi da moderata a severa elegibili per il trattamento con farmaci biologici

E.4

Principal exclusion criteria

Breast feeding women
Women planning a pregnancy
History of cancer

Donne in età fertile che non assumono una contraccezione efficace
Donne in allattamento
Pazienti con storia di neoplasia in atto o inferiore a 5 anni

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients in the 2 treatment arms that reaches the status of "Minimal Disease Activity" (MDA) after 12 weeks of treatment. MDA represents a composite index consisting of 7 points comprising 7 variables (see: Coates LC et al. Ann Rheum Dis 2010; 69: 48-53). In detail, it is considered achieved the status of MDA (efficacy criterion) when 5 of the 7 following criteria are satisfied: N° of tender joints (range 0-68) = 1; of swollen joints (range 0-66) = 1; Body Surface Area (BSA; range 0-100) = 3; VAS articular pain (range 0-100) = 15; VAS global activity disease defined by the patient (range 0-100) = 20; "Health Assessment Questionnaire (HAQ; 0-3) = 0.3; enthesis pain on palpation (Leeds Enthesitis Index; range 0-6) = 1.

proporzione di pazienti nei 2 bracci di trattamento che raggiunge lo stato di “Minimal Disease Activity” (MDA) dopo 12 settimane di trattamento. MDA rappresenta un indice composito costituito da 7 punti che prende in considerazione 7 variabili (vedi: Coates LC et al. Ann Rheum Dis 2010; 69: 48–53). In dettaglio, si ritiene raggiunto lo stato di MDA (criterio di efficacia) quando vengono soddisfatti 5 dei 7 seguenti criteri: N° di articolazioni dolenti (range 0-68) = 1; N° di articolazioni tumefatte (range 0-66) = 1; Body Surface Area (BSA; range 0-100) = 3; VAS dolore articolare (range 0-100) = 15; VAS attività globale malattia definita dal paziente (range 0-100) = 20; “Health assessment questionnaire “ (HAQ; 0-3) = 0,3; entesi dolenti alla palpazione (Leeds Enthesitis Index; LEI range 0-6) = 1

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

12 settimane

E.5.2

Secondary end point(s)

evaluate the proportion of patients in the 2 treatment arms that maintains a state of MDA at weeks 24, 48, 72; Safety assessment, through the registration of the number and type of emerging adverse events, with particular reference to those possibly or certainly related to the drugs administration.number and type of adverse events emerged in the course of the study. Since the biological drugs may have putative immunosuppressive effects, further specific endpoints of safety include: a) alterations of the response to "recall" antigens (i.e. CMV; EBV; Flu; Candida); b) the onset of severe infections (needing i.v. antibiotic therapy or hospitalisation).; o assess the possible modifications of a series of
soluble and cellular biomarkers involved in the pathogenesis of psoriatic disease after 12, 24 and 48 weeks of treatment considering significant variations =20% of the values of biomarkers studied at weeks 12, 24 and 48

valutare la proporzione di pazienti nei 2 bracci di trattamento che mantiene uno stato di MDA nelle tempistiche successive alla settimana 12 (settimane: 24, 48, 72); La sicurezza sarà valutata attraverso la registrazione della numerosità e tipologia degli eventi avversi, con particolare riferimento a quelli riconducibili alle terapie somministrate; per valutare le possibili modifichedi una serie di biomarcatori solubili e cellulari potenzialmente coinvolti nella patogenesi della malattia psoriasica dopo 12, 24, 48 settimane. Variazioni > 20% saranno considerate signifciative

E.5.2.1

Timepoint(s) of evaluation of this end point

24-48-72 weeks; within 36 months; 12, 24, 48 weeks

24-48-72 settimane; entro 36 mesi; 12, 24, 48 settimane

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

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

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)

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

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

Information not present in EudraCT

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

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:

100

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

154

F.4.2

For a multinational trial

F.4.2.1

In the EEA

154

F.4.2.2

In the whole clinical trial

154

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)

current clinical practice

normale pratica clinica

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

2018-09-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-24

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

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