Clinical Trials Register

Summary
EudraCT Number:	2016-002984-32
Sponsor's Protocol Code Number:	FER-COM-16-004
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-02-05
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

2016-002984-32

A.3

Full title of the trial

Treatment of the Reynaud's Disease associated with ischemic ulcers in patients affected by sistemic sclerosis

Trattamento del Fenomeno di Raynaud a rischio di ulcere ischemiche in pazienti con sclerosi sistemica

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

FER-COM-16-004

A.5.4

Other Identifiers

Name:

Number:

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	UNIVERSITÀ CATTOLICA DEL SACRO CUORE- POLICLINICO A. GEMELLI
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	Azienda Farmaceutica: ITALFARMACO
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	CLINICAL TRIAL CENTER
B.5.2	Functional name of contact point	CRO ACCADEMICA
B.5.3	Address:
B.5.3.1	Street Address	L.GO A. GEMELLI 8
B.5.3.2	Town/ city	ROMA
B.5.3.3	Post code	00168
B.5.3.4	Country	Italy
B.5.4	Telephone number	0688805566
B.5.5	Fax number	0688805567
B.5.6	E-mail	betty.polikar@policlinicogemelli.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	ENDOPROST - 0.05 MG/0.5 ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FIALA
D.2.1.1.2	Name of the Marketing Authorisation holder	ITALFARMACO S.P.A.
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	ENDOPROST
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ILOPROST TROMETAMOL
D.3.9.1	CAS number	73873-87-7
D.3.9.2	Current sponsor code	ND
D.3.9.3	Other descriptive name	ILOPROST SALE DI TROMETAMOLO
D.3.9.4	EV Substance Code	SUB14185MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(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	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	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	Yes
D.2.1.1.1	Trade name	ENDOPROST - 0.05 MG/0.5 ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FIALA
D.2.1.1.2	Name of the Marketing Authorisation holder	ITALFARMACO S.P.A.
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	ENDOPROST
D.3.2	Product code	ND
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ILOPROST TROMETAMOL
D.3.9.1	CAS number	73873-87-7
D.3.9.2	Current sponsor code	ND
D.3.9.3	Other descriptive name	ILOPROST SALE DI TROMETAMOLO
D.3.9.4	EV Substance Code	SUB14185MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(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.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

SISTEMIC SCLEROSIS

SCLEROSI SISTEMICA

E.1.1.1

Medical condition in easily understood language

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10042953
E.1.2	Term	Systemic sclerosis
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

To confirm the efficacy, the safety and the feasibility of the slow infusion of Iloprost done at home, using the portable syringe pump INFONDE® in a group of patients affected by systemic sclerosis.

Confermare l’efficacia, la sicurezza e la fattibilità dell’infusione lenta di Iloprost a domicilio mediante pompa siringa portatile INFONDE® in un gruppo di pazienti affetti da sclerosi sistemica

E.2.2

Secondary objectives of the trial

• Patients’ Quality of Life, measured with the HAQ ( Health Assessment Questionnaire
• Pharmacoeconomic assessments, related to the probable resources savings (direct and indirect costs), linked to the treatment made at home.

Qualità della vita dei pazienti, misurata mediante il questionario HAQ (Health Assessment Questionnaire)
 Valutazioni di farmacoeconomia, relative al probabile risparmio di risorse (costi diretti ed indiretti) , ottenibile con il trattamento domiciliare

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed Consent personally signed and dated by the patient, before any study procedure is implemented
2. Diagnosis of Raynaud’ Disease, with or without presence of acral ulcers
3. Age ≥ 18 and ≤ 80 years
4. Check for proper venous assets (rated by experienced personnel) or central venous access
5. Women of childbearing potential not willing to become pregnant during the course of the study and for 1 month following its completion
6. Men having a relationship with women of childbearing age, who are willing not to get pregnant during the course of the study and for 1 month following its completion

Consenso Informato firmato e datato dal paziente, prima di iniziare qualsiasi procedura prevista dallo studio
2. Diagnosi di sclerodermia con Fenomeno di Raynaud, con presenza o meno di ulcere acrali
3. Età ≥ 18 anni e ≤ 80 anni
4. Verifica di patrimonio venoso adeguato (valutato da personale esperto) o dell’accesso venoso centrale
5. Donne in età fertile disposte a non iniziare una gravidanza durante il corso dello studio e per 1 mese successivo al suo completamento
6. Uomini che hanno una relazione con donne in età fertile che sono disposti a non procurare una gravidanza durante il corso dello studio e per 1 mese successivo al suo completamento

E.4

Principal exclusion criteria

1. Patients with a disease characterized by advanced stages of deformation
2. Contraindications to treatment with Iloprost and / or hypersensitivity to the active substance or to any of the excipients (trometamol, ethanol, 96% (v / v), sodium chloride, hydrochloric acid)
3. Chronic renal failure (GFR <30 ml / min
4. Liver Cirrhosis
5. Surgery planned or executed by less than 3 months after initiation of treatment to the central nervous system and / or the eye; trauma surgery associated with large wounds exposed
6. Severe Thrombocytopenia (PLT <20,000 / mmc) or severe anemia (Hb <8 g / dl)
7. Severe and not controlled arterial hypertension
8. Orthostatic hypotension
9. Cephalalgia type of pathology and / or chronic vertigo evaluated by a reference specialist and / or for which the patient is undergoing a drug treatment
10. Gastrointestinal pathology in acute phase
11. Pregnancy and / or breast-feeding
12. Severe coronary heart disease or unstable angina, myocardial infarction within six months preceding the start of treatment, acute or chronic congestive heart failure (NYHA II - IV), severe arrhythmias or relevant for prognosis
13. Severe ischemic disorders of the lower limbs (grade III and IV)
14. Smoking Patients with high levels of daily consumption and not willing to abstain during the treatment period
15. Severe coagulation disorders, who need a stable regimen of treatment with anticoagulants or platelet aggregation inhibitors
16. Patients with a neurological condition that makes them incapable of understanding the nature, purpose and possible consequences of the study
17. Congestive heart failure

Pazienti con malattia caratterizzata da stati di deformazione avanzati
2. Controindicazioni al trattamento con Iloprost e/o ipersensibilità al principio attivo o ad uno qualsiasi degli eccipienti (trometamolo; etanolo, 96% (v/v); cloruro di sodio; acido cloridrico)
3. Insufficienza renale cronica (VFG< 30 ml/min)
4. Cirrosi epatica
5. Intervento chirurgico previsto o eseguito da meno di 3 mesi dall’inizio del trattamento al sistema nervoso centrale e/o all’occhio; chirurgia traumatica associata a grandi ferite esposte
6. Piastrinopenia severa (PLT <20000/mmc) o anemia severa (Hb <8 g/dl)
7. Ipertensione arteriosa grave non controllata
8. Ipotensione ortostatica
9. Patologia di tipo cefalgico e/o vertigini croniche valutate da specialista di riferimento e/o per le quali il paziente risulta in trattamento farmacologico
10. Patologia gastrointestinale in fase acuta
11. Gravidanza e/o allattamento
12. Coronaropatie gravi o angina instabile, infarto del miocardico nei sei mesi precedenti l’inizio del trattamento, insufficienza cardiaca congestizia acuta o cronica (NYHA II - IV), aritmie gravi o rilevanti per la prognosi
13. Patologie ischemiche severe degli arti inferiori (grado III e IV)
14. Pazienti fumatori, con elevati livelli di consumo quotidiano e non disposti all’astensione durante il periodo del trattamento
15. Patologie coagulative severe, che necessitino un regime stabile di trattamento con anticoagulanti o inibitori dell’aggregazione piastrinica
16. Pazienti affetti da una condizione neurologica che li renda incapaci di comprendere la natura, lo scopo e le possibili conseguenze dello studio
17. Scompenso cardiaco congestizio

E.5 End points

E.5.1

Primary end point(s)

Raynaud’s Disease intensity, evaluated through the Raynaud’s Condition Score (RCS)

Intensità del Fenomeno di Raynaud (FR) valutato mediante la Raynaud’s Condition Score (RCS)

E.5.1.1

Timepoint(s) of evaluation of this end point

18 MONTHS

18 MESI

E.5.2

Secondary end point(s)

 Ischemic ulcers incidence observed at 6 months of follow-up  Recovery time of the observed ischemic ulcers  Frequency and duration of the Raynaud’s Disease, evaluated through the Raynaud’s Condition Score (RCS)  Patients’ Quality of Life, measured with the HAQ ( Health Assessment Questionnaire  Completion rate of the entire home infusion cycle  Adverse Events incidence

Incidenza di ulcere ischemiche a 6 mesi di follow-up  Tempo di guarigione delle ulcere ischemiche in studio  Frequenza e durata del Fenomeno di Raynaud (FR), valutato mediante la Raynaud’s Condition Score (RCS)  Qualità della vita misurata mediante il questionario HAQ (Health Assessment Questionnaire)  Tasso di completamento dell’intero ciclo di infusione a domicilio  Incidenza di eventi avversi

E.5.2.1

Timepoint(s) of evaluation of this end point

18 MONTHS

18 MESI

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

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

STESSO FARMACO MA SOMMINISTRATO ATTRAVERSO POMPA DI INFUSIONE

SAME DRUG ADMINISTRATED BY MEDICAL DEVICE

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

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

CLINICAL STUDY REPORT

DISPONIBILITA' DEL CLINICAL STUDY REPORT

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:

200

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2018-02-05.

Yes

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

238

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

238

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)

NORMAL 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

2016-12-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-02-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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