Clinical Trials Register

Summary
EudraCT Number:	2019-001773-90
Sponsor's Protocol Code Number:	MiCROBPsA
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-17
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

2019-001773-90

A.3

Full title of the trial

Metagenomic analysis of the gut microbiota in patients with psoriatic arthritis upon treatment with the jak-stat inhibitor tofacitinib: correlations with immunological, clinical and imaging markers

Analisi metagenomica del microbiota intestinale in pazienti affetti da Artrite Psoriasica in trattamento con Tofacitinib e correlazioni con markers immunologici, clinici ed ecografici

A.3.1

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

Analysis of Gut bacteria in patients with psoriatic arthritis upon treatment with tofacitinib correlations with serologic, clinical and ultrasound markers of disease activity

Analisi della flora batterica intestinale in pazienti affetti da Artrite Psoriasica in trattamento con tofacitinib e correlazione con indici sierologici, clinici ed ecografici dell'attività di malattia

A.3.2

Name or abbreviated title of the trial where available

MiCROBPsA

A.4.1

Sponsor's protocol code number

MiCROBPsA

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	AZIENDA OSPEDALIERA SANT'ANDREA
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	PFIZER Srl
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	Azienda Ospedaliera Sant'Andrea
B.5.2	Functional name of contact point	UOC Medicina Interna
B.5.3	Address:
B.5.3.1	Street Address	via di Grottarossa 1035
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00189
B.5.3.4	Country	Italy
B.5.4	Telephone number	0633776043
B.5.5	Fax number	0633775531
B.5.6	E-mail	bruno.lagana@uniroma1.it

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	XELJANZ -
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER EUROPE MA EEIG
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	Tofacitinib
D.3.2	Product code	[N.A]
D.3.4	Pharmaceutical form	Film-coated 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.3.9.1	CAS number	477600-75-2
D.3.9.2	Current sponsor code	Tofacitinib
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	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	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

Psoriatic Arthritis

Artrite Psoriasica

E.1.1.1

Medical condition in easily understood language

Psoriatic arthritis

Artrite psoriasica

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

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

Aim of this prospective study is to analyse the variety and composition of the gut microbiota in PsA patients before and upon treatment with the jak-stat inhibitor tofacitinib throughout a 1-year follow-up.

Scopo dello studio è analizzare la varietà e composizione del microbiota intestinale in pazienti affetti da artrite psoriasica in terapia con l'inibitore jak-stat tofacitinib durante un follow-up di 1 anno.

E.2.2

Secondary objectives of the trial

Correlations between the gut microbiota composition and validated immunological/clinical and US parameters of disease activity will also be evaluated aiming at identifying possible predictors markers of tofacitinib effectiveness.

Verranno valutate eventuali correlazioni tra la composizione del microbiota intestinale e validati indici di attività di malattia sierologici, clinici ed ecografici al fine di identificare potenziali predittori di efficacia terapeutica.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female, 18 to 65 years of age, inclusive
- PsA diagnosis according to the CASPAR criteria, moderate to severe activity (more than 4 swollen joints and/or DAPSA = 15 and/or ASDASpcr = 1.3 and/or BASDAI =4),
- able to understand the study procedures and sign the informed consent.
- Current therapy with methotrexate at standard dosage.
- Inadequate responder, as for EULAR response criteria, to at least six months methotrexate therapy at standard dosage

- Maschi o femmine di età compresa tra i 18 e 65 anni
- diagnosi di artrite psoriasica secondo i criteri CASPAR, con attività di malattia moderato/severa (> 4 articolazioni tumefatte, e/o DAPSA = 15 e/o ASDASpcr = 1.3 e/o BASDAI =4),
- capaci di comprendere le procedure dello studio e firmare il consenso informato
- concomitante terapia con methotrexate a dosaggio standard
- inadeguata risposta secondo i criteri EULAR ad almeno 6 mesi di terapia con methotrexate a dosaggio standard

E.4

Principal exclusion criteria

- Any sort of contraindications to tofacitinib at the time of enrolment as for local label (SmPc), hypersensitivity to the active substance or to any of the excipients, active tuberculosis, serious infections such as sepsis or opportunistic infections, severe hepatic impairment, pregnancy and lactation, malignancies, known risk factors for VTE, any uncontrolled clinically significant laboratory abnormality, experiencing intolerance to MTX

- Qualsiasi controindicazione all'utilizzo del tofacitinib al momento dell'arruolamento come per RCP, ipersensibilità al principio attivo o qualsiasi eccipiente, tubercolosi attiva o altre infezioni in atto come sepsi o infezioni opportunistiche, disfunzione epatica severa, gravidanza e allattamento, neoplasie, fattori di rischio tromboembolico, qualsiasi significativa alterazione dei parametri di laboratorio, intolleranza al MTX

E.5 End points

E.5.1

Primary end point(s)

The mean change from baseline in microbial diversity and the mean microbial variations at each taxonomic level at T2 and T4

Modificazioni medie dal basale nella varietà del microbiota intestinale e la composizione ad ogni livello tassonomico al T2 e T4

E.5.1.1

Timepoint(s) of evaluation of this end point

At six and twelve months from baseline visit (T2 and T4)

Sei e 12 mesi dalla visita basale (T2 e T4)

E.5.2

Secondary end point(s)

Correlations between gut micro-organisms variations at each taxonomic level, and disease activity changes from baseline at T2 and T4 in particular:
DAPSA, BASDAI, ASDAS at the clinical examination, power-doppler signal, synovial hypertrophy and tendon thickness at the ultrasonography

Correlazioni tra le modificazioni nella composizione del microbiota intestinale ad ogni livello tassonomico e le modificazioni dell'attività di malattia al T2 e T4, in particolare:
DAPSA, BASDAI, ASDAS valutate clinicamente, segnale power doppler, sinovite proliferativa, spessore tendineo all'inserzione, all'ecografia

E.5.2.1

Timepoint(s) of evaluation of this end point

At six and twelve months from baseline visit (T2 and T4)

Sei e 12 mesi dalla visita basale (T2 e T4)

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

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

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

Yes

E.8.1.7.1

Other trial design description

Non è presente un braccio di controllo nel disegno dello studio in quanto la valutazione viene effet

There are no comparator and control arm because the same patients will be evaluated before and durin

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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:

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)

Patients will be treated as for GCP

I pazienti saranno trattati come da norme di GCP

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

2020-03-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-11-21

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

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