Clinical Trials Register

Summary
EudraCT Number:	2016-005184-13
Sponsor's Protocol Code Number:	50129
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

2016-005184-13

A.3

Full title of the trial

METRO STUDY - MESOGLYCAN VERSUS PLACEBO IN
SECONDARY PREVENTION OF SURFACE VEIN THROMBOSIS

STUDIO METRO - MESOGLICANO VERSUS PLACEBO NELLA
PREVENZIONE SECONDARIA DELLA TROMBOSI VENOSA SUPERFICIALE

A.3.1

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

METRO STUDY - MESOGLYCAN VERSUS PLACEBO IN
SECONDARY PREVENTION OF SURFACE VEIN THROMBOSIS

STUDIO METRO - MESOGLICANO VERSUS PLACEBO NELLA
PREVENZIONE SECONDARIA DELLA TROMBOSI VENOSA SUPERFICIALE

A.3.2

Name or abbreviated title of the trial where available

METRO

A.4.1

Sponsor's protocol code number

50129

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	MEDIOLANUM FARMACEUTICI S.P.A.
B.1.3.4	Country	Italy
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	Mediolanum Farmaceutici s.p.a.
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	Mediolanum Farmaceutici s.p.a.
B.5.2	Functional name of contact point	Nicoletta Iori
B.5.3	Address:
B.5.3.1	Street Address	Via San Giuseppe Cottolengo, 15
B.5.3.2	Town/ city	Milanoi
B.5.3.3	Post code	20143
B.5.3.4	Country	Italy
B.5.4	Telephone number	89132106
B.5.5	Fax number	89132375
B.5.6	E-mail	n.iori@mediolanum-farma.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	Yes
D.2.1.1.1	Trade name	PRISMA
D.2.1.1.2	Name of the Marketing Authorisation holder	Mediolanum Farmaceutici 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	Prisma
D.3.2	Product code	[B01AB]
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	Mesoglicano
D.3.9.2	Current sponsor code	B01AB
D.3.9.3	Other descriptive name	Mesoglican
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	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	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

patients with SVT of the lower limbs that have completed the acute
phase treatment cycle

pazienti affetti da TVS degli arti inferiori che abbiano completato il ciclo
di terapia della fase acuta

E.1.1.1

Medical condition in easily understood language

Patients with Superficial Vein Thrombosis of the lower limbs that have
completed the acute phase treatment cycle

pazienti affetti da Trombosi Venosa Superficiale degli arti inferiori che
abbiano completato il ciclo di terapia della fase acuta

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

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

Demonstrate the superiority of mesoglycan (Prisma), compared to
placebo in reducing the incidence of complications
thromboembolic (relapsed / extension TVS, DVT, PE) in patients who
have completed the treatment phase of the cycle
acute after a superficial vein thrombosis (SVT).

Dimostrare la superiorità del mesoglicano (Prisma®), rispetto al
placebo, nel ridurre l'incidenza di complicanze tromboemboliche
(recidiva / estensione di TVS, TVP, EP) in pazienti che abbiano
completato il ciclo di terapia della fase acuta dopo una trombosi venosa
superficiale (TVS).

E.2.2

Secondary objectives of the trial

Cumulative occurrence of the first event between: recurrence or
extension, asymptomatic or symptomatic, TVS, new proximal / distal
DVT (asymptomatic or symptomatic), pulmonary embolism (fatal / nonfatal
symptomatic); modification of the score rVCSS (effectiveness) and
Veines / Sym-QOL (quality of life) in the treatment and in the following
12 months; recanalization of the affected vein primary thrombotic event;
New development of deep venous reflux and / or surface; impact of
elastic compression therapy; contribution to the levels of CRP in
predicting the primary endpoint onset.

Evenienza cumulativa del primo evento tra: recidiva o estensione,
asintomatica o sintomatica, di TVS, nuova TVP prossimale/distale
(asintomatica o sintomatica), embolia polmonare (fatale / non fatale
sintomatica); modificazione dello score rVCSS (efficacia) e VEINES/Sym
QoL (qualità della vita) in trattamento e nei 12 mesi successivi;
ricanalizzazione della vena interessata all'evento trombotico primario;
nuovo sviluppo di reflusso venoso profondo e/o superficiale; impatto
della terapia elasto-compressiva; contributo dei livelli della PCR nel
predire l'insorgenza dell'end-point primario.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects of both sexes, aged> = 18 years
2. With previous diagnosis of SVT of the lower limbs documented with
Eco-color-Doppler (CCDU), which was the debut of at least 5 cm
extension and at least 3 cm from the saphenous junctions (magna
saphenous vein and the small saphenous vein)
3. who have completed the initial course of therapy with fondaparinux
2.5 mg / day for 45 days, as required by the latest Lines International
Guide (ACCP).
4. That the CCDU to screening do not present a concurrent involvement
of the deep venous system, or an extension of the initial TVS

1. Soggetti di entrambi i sessi, di età>=18 anni, Con pregressa diagnosi
di TVS degli arti inferiori documentata con Eco-color-Doppler (CCDU),
2. Che all'esordio fosse di almeno 5 cm di estensione e almeno a 3 cm
dalle giunzioni safeniche (vena safena magna e piccola safena),
3. che abbiano completato il ciclo terapeutico iniziale con
Fondaparinux 2.5 mg/die per 45 gg, come previsto dalle più recenti
Linee Guida internazionali (ACCP).
4. Che alla CCDU allo screening non presentino un concomitante
coinvolgimento del circolo venoso profondo, o una estensione della TVS
iniziale.

E.4

Principal exclusion criteria

1. Poor compliance to treatment of TVS,
2. life expectancy <24 months,
3. deficient cooperation anticipated or inability to complete the
questionnaires,
4. pregnancy, breast-feeding or plan to become pregnant during the
study,
5. severe locomotor disability or prolonged immobilization,
6. participation in another study over the past three months,
7. and not suspendable post-thrombotic syndrome with overt "Villalta
score"> 4,
8. chronic lymphedema of the lower limbs,
9. recent (<3 months) or planned intervention drip-surgery or
angioplasty trans-luminary percutaneous arterial
(PTA),
10. dialysis treatment in progress,
11. state of malabsorption / malnutrition,
12. Chronic use of anticoagulants and non-suspendable, phlebotrophic,
corticosteroids or NSAIDs, dual-antiplatelet therapy or ASA > 160mg /
day, centrally acting analgesics,
13. individuals with hypersensitivity to mesoglycan, heparin or
heparinoids, galactose intolerance or lactase deficiency, carriers of
diseases and hemorrhagic diathesis

1. Scarsa compliance al trattamento della TVS,
2. spettanza di vita < 24 mesi,
3. anticipata carente collaborazione o impossibilità a compilare i
questionari,
4. gravidanza, allattamento o gravidanza programmata durante la
durata dello studio,
5. grave disabilità locomotoria o immobilizzazione prolungata,
6. partecipazione ad un altro studio negli ultimi 3 mesi,
7. e non sospendibile sindrome post-trombotica conclamata con
"Villalta score" > 4,
8. linfedema cronico degli arti inferiori,
9. recente (< 3 mesi) o programmato intervento flebo-chirurgico o
angioplastica trans-luminare percutanea arteriosa (PTA),
10. trattamento dialitico in corso,
11. stato di malassorbimento/malnutrizione,
12. uso cronico e non sospendibile di anticoagulanti, flebotropi,
corticosteroidi o FANS, doppia-antiaggregazione o ASA >160mg/die,
antidolorifici ad azione centrale,
13. soggetti con ipersensibilità al mesoglicano, eparina o eparinoidi,
intolleranti al galattosio o con deficit di lattasi, portatori di diatesi e
malattie emorragiche.

E.5 End points

E.5.1

Primary end point(s)

Cumulative occurrence of the first event, with instrumental confirmation,
which occurred during the study treatment including: recurrence or
extension, asymptomatic or symptomatic, TVS, new DVT (asymptomatic
or symptomatic proximal / distal symptomatic isolated), pulmonary
embolism (fatal / non-fatal symptomatic ).

Evenienza cumulativa del primo evento, con conferma strumentale,
verificatosi durante il trattamento in studio tra: recidiva o estensione,
asintomatica o sintomatica, di TVS, nuova TVP (prossimale asintomatica
o sintomatica / distale isolata sintomatica), embolia polmonare (fatale /
non fatale sintomatica).

E.5.1.1

Timepoint(s) of evaluation of this end point

During the treatment period in days: 30, 60, 135, 225, 315 (+ -5gg) after
randomization, and in the period of follow-up at 3, 6 and 9 months after
the end of treatment and then every 6 months until the end of the study,
subjects will be contacted by telephone by staff trained to assess their
compliance with treatment, the possible use of drugs not allowed and
the occurrence of adverse events and / or end-points of the study

Durante il periodo di trattamento nei giorni: 30, 60, 135, 225, 315 (+-
5gg) dalla randomizzazione, e nel periodo di follow-up a distanza di 3, 6
e 9 mesi dal termine del trattamento e poi ogni 6 mesi fino al termine
dello studio, i soggetti verranno contattati telefonicamente da personale
addestrato per valutarne la compliance al trattamento, l'eventuale
utilizzo di farmaci non permessi e l'insorgenza di eventi avversi e/o endpoints
dello studio

E.5.2

Secondary end point(s)

Cumulative occurrence of the first event between: recurrence or
extension, asymptomatic or symptomatic, TVS, new proximal / distal
DVT (asymptomatic or symptomatic), pulmonary embolism (fatal / nonfatal
symptomatic); modification of the score rVCSS (effectiveness) and
Veines / Sym-QOL (quality of life) in the treatment and in the following12 months; recanalization of the affected vein primary thrombotic event;
New development of deep venous reflux and / or surface; impact of
elastic compression therapy; contribution to the levels of CRP in
predicting the primary endpoint onset.

Evenienza cumulativa del primo evento tra: recidiva o estensione,
asintomatica o sintomatica, di TVS, nuova TVP prossimale/distale
(asintomatica o sintomatica), embolia polmonare (fatale / non fatale
sintomatica); modificazione dello score rVCSS (efficacia) e VEINES/Sym-
QoL (qualità della vita) in trattamento e nei 12 mesi successivi;
ricanalizzazione della vena interessata all'evento trombotico primario;
nuovo sviluppo di reflusso venoso profondo e/o superficiale; impatto
della terapia elasto-compressiva; contributo dei livelli della PCR nel
predire l'insorgenza dell'end-point primario.

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

Yes

E.6.3

Therapy

Yes

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)

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

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

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

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 subjects enrolled and randomized come out permanently from the
study on the occurrence of any of the following events:occurrence of
one of the primary end-points (before the end of follow-up),onset of
one of the exclusion criteria,SAE that carries one of the exclusion
criteria,withdrawal of consent to participation in the
study.Discontinuation of study treatment for several reasons the event
listed above will not constitute a valid reason for the patient's exit from
the study.

I soggetti arruolati e randomizzati usciranno in modo permanente dallo
studio al verificarsi di uno qualsiasi dei seguenti eventi: occorrenza di
uno degli end-point primari (prima della fine del follow-up),insorgenza
di uno dei criteri di esclusione,un SAE che realizzi uno dei criteri di
esclusione,ritiro delconsenso alla partecipazione dello studio.

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:

450

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

650

F.4.2

For a multinational trial

F.4.2.1

In the EEA

650

F.4.2.2

In the whole clinical trial

650

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)

none

nessuno

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

2017-11-29

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	Ongoing

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