Clinical Trials Register

Summary
EudraCT Number:	2017-002809-34
Sponsor's Protocol Code Number:	EPA-Pol-04
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:	2018-11-07
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

2017-002809-34

A.3

Full title of the trial

Randomised, double-blind, placebo-controlled study of the, efficacy, safety and tolerability of EPA-FFA gastro-resistant capsules, in patients with familial adenomatous polyposis (FAP)

Studio randomizzato in doppio cieco controllato verso placebo dell’efficacia, sicurezza e tollerabilità delle capsule gastroresistenti di EPA-FFA in pazienti con poliposi adenomatosa familiare (FAP)

A.3.1

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

Effects of EPA-FFA on polypectomy in familial adenomatous polyposis

Effetti di EPA-FFA sulla polipectomia nella poliposi adenomatosa familiare (FAP)

A.3.2

Name or abbreviated title of the trial where available

Effects of EPA-FFA on polypectomy in familial adenomatous polyposis

Effetti di EPA-FFA sulla polipectomia nella poliposi adenomatosa familiare (FAP)

A.4.1

Sponsor's protocol code number

EPA-Pol-04

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/281/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	S.L.A. PHARMA
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	SLA Pharma UK Limited
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	SLA Pharma UK Limited
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Ground Floor, Building 5, Leavesden Park, Hercules Way, Hertfordshire
B.5.3.2	Town/ city	Leavesden
B.5.3.3	Post code	WD25 7GS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441923681001
B.5.5	Fax number	00441923616950
B.5.6	E-mail	jslagel@slapharma.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/666
D.3 Description of the IMP
D.3.1	Product name	Eicosapentaenoic acid
D.3.2	Product code	[EPA]
D.3.4	Pharmaceutical form	Gastro-resistant capsule, soft
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	Icosapent
D.3.9.1	CAS number	25378-27-2
D.3.9.2	Current sponsor code	EPA
D.3.9.3	Other descriptive name	Eicosapentaenoic acid
D.3.9.4	EV Substance Code	SUB13664MIG
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	500
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	Yes
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	Gastro-resistant capsule, soft
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

Familial Adenomatous Polyposis (FAP)

Poliposi adenomatosa familiare

E.1.1.1

Medical condition in easily understood language

Familial adenomatous polyposis

Poliposi adenomatosa familiare

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10059327
E.1.2	Term	Familial adenomatous polyposis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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

To determine the efficacy of EPA-FFA gastroresistant capsules in patients with FAP in reducing polypectomy.

Stabilire l’efficacia di capsule di EPA-FFA gastroresistenti nella riduzione della polipectomia in pazienti con FAP

E.2.2

Secondary objectives of the trial

• Evaluate the clinical disease progression.
• Evaluate the long-term safety and tolerability of EPA-FFA.

• Valutare la progressione clinica della malattia.
• Valutare la sicurezza e la tollerabilità a lungo termine dell’EPA-FFA.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Must give written informed consent.
2.Male or female subjects, 18 to 65 years of age.
3.Known diagnosis of FAP defined as those with a pathogenic APC mutation.
4.Patients have had a previous colectomy with an ileo-rectal anastomosis or an ileo pouch-anal anastomosis with a rectal remnant of = 2 cm.
5.Classified stage 1-3 on InSiGHT Polyposis Staging System (IPSS).
6.Subjects must show a willingness to abstain from regular use of non-steroidal anti-inflammatory medication for the trial. A cardioprotective dose of aspirin (75mg-100mg) will be permitted.

1. Devono dare un consenso informato per iscritto.
2. Soggetti maschi e femmine, da 18 a 65 anni.
3. Diagnosi di FAP nota definita come tipo con mutazione patogena del gene APC.
4. I pazienti con precedente colectomia con anastomosi ileo-rettale o anastomosi sacca ileo-anale con un residuo rettale di = 2 cm .
5. Classificati come stadio 1-3 con il Sistema di Stadiazione della Poliposi InSiGHT (IPSS).
6. I soggetti devono mostrare la volontà di astenersi dall’uso regolare di farmaci antinfiammatori non steroidei durante la sperimentazione. Sarà permessa una dose di aspirina cardioprotettiva (75 mg - 100 mg).

E.4

Principal exclusion criteria

1.Subjects with ileo-rectal anastomosis who have = 20 polyps which are of >5mm that are not amendable to removal in the rectum.
2.Subjects unwilling to have regular endoscopic examination.
3.Subjects who are due to undergo gastro-intestinal surgery related to FAP.
4.History of invasive carcinoma in the past 3 years.
5.History of pelvic radiation.
6.Known allergic reaction or intolerant to fish or fish oils.
7.Known allergic reaction to excipients of IMP and placebo.
8.Subjects who are pregnant or breast-feeding at screening.
9.Subjects taking aspirin, other than a low (75mg-100mg) cardioprotective dose on a regular basis, or other non-steroidal anti-inflammatory drugs (NSAIDs) on a regular basis. Regular use of other NSAIDS is defined in this protocol as use greater than 14-day treatment period, and one treatment per six months for the duration of the study.
10.Subjects taking NSAIDs regularly in the 3 months prior to entry (other than low dose aspirin).
11.Subjects taking NSAID, 5-aminosalicylic acid (5-ASA or mesalamine).
12.Subjects who are taking other fish-oil supplements (e.g. cod liver oil) who are unwilling to stop them for the duration of the study. Subjects previously taking fish oil must have a washout period of 2 months prior to study enrolment.
13.Subjects who are taking warfarin or other anticoagulants.
14.Experimental agents must have been discontinued at least 8 weeks prior to screening for a period equivalent to 5 half-lives of the agent (whichever is longer).
15.Subjects suffering from known disorders of clotting and blood coagulation
16.Subjects who have significant abnormalities on their screening blood tests.
17.Subjects with gastrointestinal malabsorptive disease.
18.Subjects with uncontrolled hypercholesterolaemia.
19.Subjects who are deemed mentally incompetent, or have a history of anorexia nervosa or bulimia.
20.Subjects who will be unavailable for the duration of the trial, deemed unable to comply with the requirements of the study protocol, likely to be noncompliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason.
21.Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless surgically sterile must use effective contraception (either combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD], intrauterine hormone-releasing system [IUS], vasectomised partner, sexual abstinence (only considered an acceptable method of contraception when it is in line with the subjects’ usual and preferred lifestyle), combination of male condom with either cap, diaphragm or sponge with spermicide [double barrier methods]), and willing and able to continue contraception for 1 month after the last administration of IMP. Women using oral contraception must have started using it at least 2 months prior to screening.
22.Women are not considered to be of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels that have been confirmed to be in the “postmenopausal range”. Or have had a surgical bilateral oophorectomy (with or without hysterectomy) or bilateral tubal ligation at least six weeks before the screening visit. In case of oophorectomy alone, the reproductive status of the woman should have been confirmed by follow up hormone level assessment.

1. Soggetti con anastomosi ileo-rettale che abbiano = 20 polipi che sono > 5mm la cui rimozione non è indicata nel retto.
2. Soggetti che non accettano di sottoporsi regolarmente ad esami sigmoidoscopici.
3. Soggetti che devono affrontare un intervento di chirurgia gastro-intestinale legato alla FAP.
4. Storia di carcinoma invasivo negli ultimi 3 anni.
5. Storia di radiazione pelvica.
6. Reazione allergica nota o intolleranza al pesce e agli oli di pesce.
7. Reazione allergica nota o intolleranza agli eccipienti dell’IMP e al placebo.
8. Soggetti in gravidanza o in allattamento durante la fase di screening.
9. Soggetti che assumono aspirina ad eccezione di una bassa dose cardioprotettiva (75mg-100mg) su base regolare, o altri farmaci antinfiammatori non steroidei (FANS) su base regolare. L’uso regolare di altri FANS è definito in questo protocollo come un trattamento per un periodo maggiore di 14 giorni e più di un trattamento ogni sei mesi per la durata dello studio.
10. Soggetti che assumono regolarmente FANS (diversi dalla dose ridotta di aspirina) nei 3 mesi precedenti all’accesso.
11. Soggetti che assumono FANS, acido 5-amminosalicilico (5-ASA o mesalazina).
12. Soggetti che stanno assumendo altri integratori a base di olio di pesce (es. Olio di fegato di merluzzo) che non desiderano interromperne l’assunzione per la durata della sperimentazione. I soggetti che hanno assunto olio di pesce in precedenza devono prevedere un periodo di wash-out di 2 mesi prima di accedere allo studio.
13. Soggetti che assumono warfarin o altri anticoagulanti.
14. Gli agenti sperimentali devono essere interrotti almeno 8 settimane prima dello screening per un periodo equivalente a 5 emivite del principio attivo (qualunque sia la più lunga).
15. Soggetti che soffrono di patologie note di trombosi e coagulazione del sangue.
16. Soggetti che presentano anomalie significative negli esami del sangue dello screening.
17. Soggetti con patologie di malassorbimento gastrointestinale.
18. Soggetti con ipercolesterolemia incontrollata.
19. Soggetti considerati mentalmente incapaci o che hanno alle spalle una storia di anoressia nervosa o bulimia.
20. Soggetti che non saranno disponibili per a durata della sperimentazione, considerati incapaci di rispettare i requisiti del protocollo di sperimentazione, con alta probabilità di non rispettare il protocollo o che sono considerati instabili dal ricercatore per qualsiasi ragione.
21. Le donne potenzialmente fertili, definite come tutte le donne fisiologicamente capaci di avere una gravidanza, se non chirurgicamente sterili, devono utilizzare un contraccettivo efficace (sia contraccettivi ormonali contenenti estrogeno e progesterone associati con inibizione dell’ovulazione [orali, intravaginali, transdermici], contraccettivi ormonali a base di solo progesterone, associati a inibizione dell’ovulazione [orali, iniettabili, impiantabili], dispositivi intrauterini [IUD], sistema intrauterino con rilascio di ormoni [IUS], partner vasectomizzato, astinenza sessuale (considerata un metodo contraccettivo affidabile se è in linea con lo stile di vita abituale o preferito dei soggetti), combinazione di condom maschili con spirale, diaframma o spugna con spermicida [metodi a doppia barriera]), che desiderano e possono continuar la contraccezione per 1 mese successivo all’ultima somministrazione dell’IMP. Le donne che utilizzano contraccettivi devono aver iniziato ad utilizzarli almeno 2 mesi prima dello screening. Le donne non sono considerate potenzialmente fertili dopo ameno 12 mesi di amenorrea naturale (spontanea) con un profilo clinico appropriato (es. età appropriata, storia di sintomi vasomotori) dopo sei mesi di amenorrea spontanea con livelli di FSH confermati come su “valori post-menopausa”. O che hanno subito ooforectomia bilaterale chirurgica (con o senza isterectomia) o legamento bilaterale delle tube almeno sei settimane prima della visita di screening. [...]

E.5 End points

E.5.1

Primary end point(s)

Total number of polypectomies (polyps > 5mm in the rectum) conducted during the 24 months study period.

Numero totale di polipectomie (polipi = 5mm nel retto) condotte durante il periodo di sperimentazione di 24 mesi.

E.5.1.1

Timepoint(s) of evaluation of this end point

Study end

Fine studio

E.5.2

Secondary end point(s)

Change in polyp number at 24 months assessed by blinded review of video records.; Change in score on the InSiGHT Polyposis Staging System (IPSS) at 24 months.; Number of subjects requiring surgical intervention (not including polypectomies).; Total number of polypectomies (polyps > 5mm in the rectum) conducted at 6 months, 12 months, 18 months.; Change in polyp number at 6 months, 12 months, 18 months assessed by blinded review of video records.; Change in score on the InSiGHT Polyposis Staging System (IPSS) at 6 months, 12 months, 18 months; Time to surgical intervention (not including polypectomies).; Change in score on the Spigelman Classification of Duodenal Polyposis at 24 months; Patient’s Global Impression of Improvement (PGI-I) at Months 6, 12, 18 and 24.

Variazione nel numero di polipi a 24 mesi valutato con esame in cieco delle registrazioni video.; Modifica della valutazione nel sistema di stadiazione della poliposi InSiGHT (IPSS) a 24 mesi.; Numero di soggetti che richiedono interventi chirurgici (escluse le polipectomie).; Numero totale di polipectomie (polipi = 5mm nel retto) condotte durante il periodo di sperimentazione di 6 mesi, 12 mesi, 18 mesi.; Variazione nel numero di polipi a 6 mesi, 12 mesi, 18 mesi valutato con esame in cieco delle registrazioni video; Modifica della valutazione nel sistema di stadiazione della poliposi InSiGHT (IPSS) a 6 mesi, 12 mesi, 18 mesi.; Intervallo prima dell’intervento chirurgico (escluse le polipectomie).; Modifica della valutazione nella classificazione Spigelman della poliposi duodenale a 24 mesi.; Impressione di miglioramento globale del paziente (PGI-I) a 6, 12, 18 e 24 mesi.

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months; 24 months; 24 months; 6, 12 and 18 months; 6,12 and 18 months; 6, 12 and 18 mos; 24 months; 24 months; 6, 12, 18 and 24 months

24 mesi; 24 mesi; 24 mesi; 6, 12 e 18 mesi; 6, 12 e 18 mesi; 6, 12 e 18 mesi; 24 mesi; 24 mesi; 6, 12, 18 e 24 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

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)

Yes

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

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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Israel

Czechia

France

Germany

Italy

Netherlands

Spain

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 end of the trial is the last patient follow-up call (28 days after the last patient Visit).

La fine dello studio è l'ultima telefonata di follow-up (28 giorni dopo l'ultima visita dell'ultimo paziente).

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:

204

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

184

F.4.2.2

In the whole clinical trial

204

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)

The subjects will be referred back to their local clinics for continued standard care. Support information will also be provided.

I soggetti saranno indirizzati alle loro cliniche locali per una continua assistenza standard. Verranno fornite anche informazioni di supporto.

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

2019-02-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-19

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2024-06-27

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