E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Adenomatous Polyposis (FAP) |
familiær adenomatøs polypose (FAP) |
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E.1.1.1 | Medical condition in easily understood language |
Familial adenomatous polyposis |
familiær adenomatøs polypose (FAP) |
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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 | 100000004850 |
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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 gastro-resistant capsules in patients with FAP in reducing polypectomy. |
• At fastslå effektiviteten af EPA-FFA gastroresistente kapsler med at reducere polypektomi hos patienter med FAP. |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the clinical disease progression. • Evaluate the long-term safety and tolerability of EPA-FFA. |
• Evaluere det kliniske sygdomsforløb. • Evaluere sikkerheden ved og tolerancen af EPA-FFA på lang sigt.
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E.2.3 | Trial contains a sub-study | No |
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 ileal pouch- anal anastomosis with a rectal remnant of ≥ 2cm. 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 cardio protective dose of aspirin (75mg-100mg) will be permitted. |
1. Skal give skriftligt informeret samtykke. 2. Mandlige eller kvindelige forsøgspersoner, 18 til 65 år. 3. Kendt FAP-diagnose, defineret som dem med en patogen APC-mutation, og som tidligere har fået foretaget en kolektomi med ileorektal anastomose. 4. Patienter har tidligere haft en kolektomi med en ileo-rektal anastomose eller en ileal pouchanal anastomose med en rektal rest på ≥ 2 cm. 5. Klassificeret trin 1-3 på InSiGHT Polyposis Staging System (IPSS). 6. Forsøgspersoner skal være villige til at afholde sig fra regelmæssig brug af ikke-steroid antiinflammatorisk medicin til forsøget. En hjertebeskyttende dosis aspirin (75 mg-100 mg) er tilladt.
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E.4 | Principal exclusion criteria |
1. In subjects with previous ileo-rectal anastomosis ≥ 20 polyps > 5mm in the rectum. 2. Subjects unwilling to have regular sigmoidoscopy 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 or other non-steroidal anti-inflammatory drugs (NSAIDs) on a regular basis other than low dose (75mg-100mg) cardioprotective dose. 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. 22. Women using oral contraception must have started using it at least 2 months prior to screening. 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. Hos forsøgspersoner med tidligere ileorektal anastomose ≥ 20 polypper > 5 mm i rektum. 2. Forsøgspersoner, der ikke er villige til at få foretaget regelmæssige sigmoideoskopi undersøgelser. 3. Forsøgspersoner, der venter på undergå FAP-relateret gastrointestinal kirurgi. 4. Anamnese med invasivt karcinom indenfor de sidste 3 år. 5. Anamnese med bækkenbestråling. 6. Kendt allergisk reaktion eller intolerans overfor fisk eller fiskeolier. 7. Kendt allergisk reaktion over IMP-hjælpestoffer og placebo. 8. Forsøgspersoner, der er gravide eller ammer ved screening. 9. Forsøgspersoner, der tager aspirin eller andre ikke-steroide antiinflammatoriske midler med jævne mellemrum, bortset fra lavdosis (75 mg-100 mg) hjertebeskyttende dosis. Regelmæssig brug af andre NSAID'er er defineret i denne protokol som anvendelse over 14 dages behandlingsperiode og en behandling pr. seks måneder i undersøgelsens varighed. 10. Forsøgspersoner, der tager NSAID'er regelmæssigt i de sidste 3 måneder før tilmelding (med undtagelse af lavdosis aspirin). 11. Forsøgspersoner, der tager NSAID, 5-aminosalicylsyre (5-ASA eller mesalamin). 12. Forsøgspersoner, der tager andre fiskeolietilskud (f.eks torskelevertran), og som ikke er villige til at stoppe med at tage dem i løbet af undersøgelsen. Forsøgspersoner, der tidligere har taget fiskeolie, skal have en udvaskningsperiode på 2 måneder før tilmelding til forsøget. 13. Forsøgspersoner, der tager warfarin eller andre antikoagulanter. 14. Eksperimentelle midler skal være stoppet mindst 8 uger før screening, i en periode svarende til 5 halveringstider for stoffet (alt efter hvad der er længere). 15. Forsøgspersoner, der lider af kendte lidelser med størkning og blodkoagulation. 16. Forsøgspersoner, der har betydelige anormaliteter i deres screeningsblodprøver. 17. Forsøgspersoner med gastrointestinal malabsorptionssygdom. 18. Forsøgspersoner med ukontrolleret hyperkolesterolæmi. 19. Forsøgspersoner, der anses for at være mentalt inkompetente, eller som har en anamnese med anoreksi eller bulimi. 20. Forsøgspersoner, der ikke er til rådighed i forsøgets varighed, der vurderes til at være ude af stand til at opfylde forsøgsprotokollens krav, som sandsynligvis ikke vil overholde protokollen, eller som investigatoren af anden grund mener at være uegnet. 21. Kvinder i den fødedygtige alder, defineret som alle kvinder, der er fysiologisk i stand til at blive gravide, medmindre de er kirurgisk sterile, skal anvende effektiv prævention (enten kombineret hormonprævention, der indeholder østrogen og progestogen forbundet med hæmning af ægløsning [oral, intravaginal, transdermal], kun hormonprævention med progestogen, der er forbundet med hæmning af ægløsning [oral, injicerbar, implanterbar], spiral [IUD], intrauterint hormonfrigivende system [IUS], vasektomeret partner, seksuel afholdenhed (betragtes kun som en acceptabel præventionsmetode, når den er i overensstemmelse med forsøgspersonens sædvanlige og foretrukne livsstil), kombination af kondom med enten hætte, membran eller svamp med sæddræbende middel [dobbelt barrieremetoder]), og som er villig og i stand til at fortsætte præventionen 1 måned efter den sidste administration af IMP. 22. Kvinder, der bruger p-piller, skal have påbegyndt brug mindst 2 måneder før screening. Kvinder betragtes ikke som værende i den fødedygtige alder, hvis de har haft 12 måneders naturlig (spontan) amenoré med en passende klinisk profil (f.eks. aldersrelevant, anamnese med vasomotoriske symptomer), eller seks måneder med spontan amenoré og serum FSH-niveauer, der er blevet bekræftet til at ligge indenfor det "postmenopausale område". Eller har haft en kirurgisk bilateral ooforektomi (med eller uden hysterektomi) eller bilateral aflukning af æggeledere mindst alene skal kvindens reproduktive status bekræftes med opfølgende vurdering af hormonniveau.
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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. |
Samlet antal polypektomier (polypper > 5 mm i rektum), der er udført i løbet af den 24 måneders forsøgsperiode. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study end. |
forsøgets afslutning |
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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.
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• Ændring i polypantallet ved 24 måneder, vurderet ved hjælp af blindet gennemgang af videooptagelser. • Ændring i score på InSiGHT Polyposis Staging System (IPSS) ved 24 måneder. • Antal forsøgspersoner, der kræver kirurgisk indgreb (ikke polypektomier). • Samlet antal polypektomier (polypper > 5 mm i rektum), der er udført ved 6 måneder, 12 måneder, 18 måneder. • Ændring i polypantallet ved 6 måneder, 12 måneder, 18 måneder, vurderet ved hjælp af blindet gennemgang af videooptagelser. • Ændring i score på InSiGHT Polyposis Staging System (IPSS) ved 6 måneder, 12 måneder, 18 måneder. • Tid til kirurgisk indgreb (ikke polypektomier). • Ændring i score på Spigelman-klassifikationen af duodenal polypose ved 24 måneder. • Patientens globale indtryk af forbedring (PGI-I) ved måned 6, 12, 18 og 24.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6, 12, 18 and 24 months. |
6 ,12,18 og 24 måneder |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 | No |
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 |
Denmark |
France |
Germany |
Italy |
Poland |
Spain |
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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
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The end of the trial is the last patient follow-up call (28 days after the last patient Visit). |
Afslutningen af forsøget er det sidste patientopfølgningsopkald (28 dage efter den sidste patientbesøg). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |