<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03806426</url>
  </required_header>
  <id_info>
    <org_study_id>EPA-POL-04</org_study_id>
    <nct_id>NCT03806426</nct_id>
  </id_info>
  <brief_title>Effect of EPA-FFA on Polypectomy in Familial Adenomatous Polyposis</brief_title>
  <official_title>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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>S.L.A. Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>S.L.A. Pharma AG</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      2 Year randomised, double-blind, placebo-controlled, parallel group study to determine the&#xD;
      safety and efficacy of EPA-FFA gastro resistant capsules in FAP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this Phase III study is to determine whether Eicosapentaenoic acid-free fatty&#xD;
      acid is a safe and well tolerated treatment in reducing the number of polypectomies FAP&#xD;
      patients with an APC gene mutation have over a 2 year treatment period and to assess the&#xD;
      effect that this has on clinical disease progression. Planned Sample Size This study will&#xD;
      enrol 204 subjects (102 subjects per treatment group). Primary Objective is to determine the&#xD;
      efficacy of EPA-FFA gastro-resistant capsules in patients with FAP in reducing polypectomy.&#xD;
&#xD;
      Secondary objectives is to evaluate the clinical disease progression and the long-term safety&#xD;
      and tolerability of EPA-FFA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 5, 2018</start_date>
  <completion_date type="Anticipated">January 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Number of Polypectomies (polyps &gt; 5mm in the rectum) conducted during the 24 months study period</measure>
    <time_frame>24 months</time_frame>
    <description>Proctectomy is indicated when polyp burden is frequently high in the remaining rectum, if large highly dysplastic polyps occur, or if frank malignancy develops. Proctocolectomy also significantly reduces the cancer risk with the removal of the colon and rectum.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Polyp number at 24 months assessed by blinded review of video records</measure>
    <time_frame>24 months</time_frame>
    <description>Subsequent proctectomy is indicated when polyp burden is frequently high in the remaining rectum, if large highly dysplastic polyps occur, or if frank malignancy develops. Proctocolectomy also significantly reduces the cancer risk with the removal of the colon and rectum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in score on the InSIGHT Polyposis Staging System (IPSS) at 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>Classified stage on InSiGHT Polyposis Staging System (IPSS). The subjects FAP will be classified in accordance with the IPSS.&#xD;
The IPSS classification will be verified by the Polyp Video Scoring committee</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">204</enrollment>
  <condition>Familial Adenomatous Polyposis</condition>
  <arm_group>
    <arm_group_label>Treatment Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eicosapentaenoic acid free fatty acid (EPA-FFA) 500mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Group B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 500mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eicosapentaenoic acid free fatty acid (EPA-FFA)</intervention_name>
    <description>500mg capsule, two 500mg capsules to be taken twice daily for 24 months</description>
    <arm_group_label>Treatment Group A</arm_group_label>
    <other_name>ALFA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>500mg capsule, two 500mg capsules to be taken twice daily for 24 months</description>
    <arm_group_label>Treatment Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Must give written informed consent.&#xD;
&#xD;
          2. Male or female subjects, 18 to 65 years of age.&#xD;
&#xD;
          3. Known diagnosis of FAP defined as those with a pathogenic APC mutation&#xD;
&#xD;
          4. Patients have had a previous colectomy with an ileo-rectal anastomosis or an ileal&#xD;
             pouch- anal anastomosis with a rectal remnant of ≥ 2cm.&#xD;
&#xD;
          5. Classified stage 1-3 on InSiGHT Polyposis Staging System (IPSS).&#xD;
&#xD;
          6. Subjects must show a willingness to abstain from regular use of non-steroidal&#xD;
             anti-inflammatory medication for the trial. A cardio protective dose of aspirin&#xD;
             (75mg-100mg) will be permitted.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with ileo-rectal anastomosis who have ≥ 20 polyps which are of &gt;5mm that are&#xD;
             not amendable to removal in the rectum.&#xD;
&#xD;
          2. Subjects unwilling to have regular sigmoidoscopy examination.&#xD;
&#xD;
          3. Subjects who are due to undergo gastro-intestinal surgery related to FAP.&#xD;
&#xD;
          4. History of invasive carcinoma in the past 3 years.&#xD;
&#xD;
          5. History of pelvic radiation.&#xD;
&#xD;
          6. Known allergic reaction or intolerant to fish or fish oils.&#xD;
&#xD;
          7. Known allergic reaction to excipients of IMP and placebo.&#xD;
&#xD;
          8. Subjects who are pregnant or breast-feeding at screening.&#xD;
&#xD;
          9. Subjects taking aspirin, other than a low (75mg-100mg) cardioprotective dose on a&#xD;
             regular basis, or other nonsteroidal anti-inflammatory drugs (NSAIDs) on a regular&#xD;
             basis. Regular use of other NSAIDS is defined in this protocol as use greater than&#xD;
             14-day treatment period, and one treatment per six months for the duration of the&#xD;
             study.&#xD;
&#xD;
         10. Subjects taking NSAIDs regularly in the 3 months prior to entry (other than low dose&#xD;
             aspirin).&#xD;
&#xD;
         11. Subjects taking NSAID, 5-aminosalicylic acid (5-ASA or mesalamine).&#xD;
&#xD;
         12. Subjects who are taking other fish-oil supplements (e.g. cod liver oil) who are&#xD;
             unwilling to stop them for the duration of the study. Subjects previously taking fish&#xD;
             oil must have a washout period of 2 months prior to study enrolment.&#xD;
&#xD;
         13. Subjects who are taking warfarin or other anticoagulants.&#xD;
&#xD;
         14. Experimental agents must have been discontinued at least 8 weeks prior to screening or&#xD;
             for a period equivalent to 5 half-lives of the agent (whichever is longer).&#xD;
&#xD;
         15. Subjects suffering from known disorders of clotting and blood coagulation.&#xD;
&#xD;
         16. Subjects who have significant abnormalities on their screening blood tests.&#xD;
&#xD;
         17. Subjects with gastrointestinal malabsorptive disease.&#xD;
&#xD;
         18. Subjects with uncontrolled hypercholesterolaemia.&#xD;
&#xD;
         19. Subjects who are deemed mentally incompetent or have a history of anorexia nervosa or&#xD;
             bulimia.&#xD;
&#xD;
         20. Subjects who will be unavailable for the duration of the trial, deemed unable to&#xD;
             comply with the requirements of the study protocol, likely to be noncompliant with the&#xD;
             protocol, or who are felt to be unsuitable by the Investigator for any other reason.&#xD;
&#xD;
         21. Women of childbearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, unless surgically sterile, must use effective contraception (either&#xD;
             combined oestrogen and progestogen containing hormonal contraception associated with&#xD;
             inhibition of ovulation [oral, intravaginal, transdermal], progestogen only hormonal&#xD;
             contraception associated with inhibition of ovulation [oral, injectable, implantable],&#xD;
             intrauterine device [IUD], intrauterine hormone-releasing system [IUS], vasectomised&#xD;
             partner, sexual abstinence (only considered an acceptable method of contraception when&#xD;
             it is in line with the subjects' usual and preferred lifestyle), combination of male&#xD;
             condom with either cap, diaphragm or sponge with spermicide [double barrier methods]),&#xD;
             and willing and able to continue contraception for 1 month after the last&#xD;
             administration of IMP.&#xD;
&#xD;
         22. Women using oral contraception must have started using it at least 2 months prior to&#xD;
             screening. Women are not considered to be of childbearing potential if they have had&#xD;
             12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile&#xD;
             (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous&#xD;
             amenorrhea with serum FSH levels that have been confirmed to be in the &quot;postmenopausal&#xD;
             range&quot;. Or have had a surgical bilateral oophorectomy (with or without hysterectomy)&#xD;
             or bilateral tubal ligation at least six weeks before the screening visit. In case of&#xD;
             oophorectomy alone, the reproductive status of the woman should have been confirmed by&#xD;
             follow up hormone level assessment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luigi Ricciardiello, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor of Gastroenterology, University of Bologna</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Justin Slagel, CEO</last_name>
    <phone>+44 1923 681001</phone>
    <email>info@slapharma.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Bologna and St.Orsola-Malpighi Hospital</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <removed_countries>
    <country>Czechia</country>
    <country>France</country>
    <country>Israel</country>
    <country>Netherlands</country>
    <country>Spain</country>
  </removed_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>October 26, 2022</last_update_submitted>
  <last_update_submitted_qc>October 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Eicosapentaenoic Acid</keyword>
  <keyword>EPA</keyword>
  <keyword>EPA 99%</keyword>
  <keyword>Fatty Acid</keyword>
  <keyword>omega-3</keyword>
  <keyword>polyp</keyword>
  <keyword>Familial Adenomatous Polyposis</keyword>
  <keyword>FAP</keyword>
  <keyword>IRA (Ileo-rectal anastomosis)</keyword>
  <keyword>PUFA (polyunsaturated fatty acid)</keyword>
  <keyword>Endoscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Nasopharyngeal Neoplasms</mesh_term>
    <mesh_term>Adenomatous Polyposis Coli</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03806426
org study id: EPA-POL-04
nct id: NCT03806426
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
2 Year randomised, double-blind, placebo-controlled, parallel group study to determine the
      safety and efficacy of EPA-FFA gastro resistant capsules in FAP.
The purpose of this Phase III study is to determine whether Eicosapentaenoic acid-free fatty
      acid is a safe and well tolerated treatment in reducing the number of polypectomies FAP
      patients with an APC gene mutation have over a 2 year treatment period and to assess the
      effect that this has on clinical disease progression. Planned Sample Size This study will
      enrol 204 subjects (102 subjects per treatment group). Primary Objective is to determine the
      efficacy of EPA-FFA gastro-resistant capsules in patients with FAP in reducing polypectomy.

      Secondary objectives is to evaluate the clinical disease progression and the long-term safety
      and tolerability of EPA-FFA.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Total Number of Polypectomies (polyps > 5mm in the rectum) conducted during the 24 months study period
time frame: 24 months
description: Proctectomy is indicated when polyp burden is frequently high in the remaining rectum, if large highly dysplastic polyps occur, or if frank malignancy develops. Proctocolectomy also significantly reduces the cancer risk with the removal of the colon and rectum.
measure: Change in Polyp number at 24 months assessed by blinded review of video records
time frame: 24 months
description: Subsequent proctectomy is indicated when polyp burden is frequently high in the remaining rectum, if large highly dysplastic polyps occur, or if frank malignancy develops. Proctocolectomy also significantly reduces the cancer risk with the removal of the colon and rectum.
measure: Change in score on the InSIGHT Polyposis Staging System (IPSS) at 24 months
time frame: 24 months
description: Classified stage on InSiGHT Polyposis Staging System (IPSS). The subjects FAP will be classified in accordance with the IPSS.
The IPSS classification will be verified by the Polyp Video Scoring committee
arm group label: Treatment Group A
arm group type: Experimental
description: Eicosapentaenoic acid free fatty acid (EPA-FFA) 500mg
arm group label: Treatment Group B
arm group type: Placebo Comparator
description: Placebo 500mg
intervention type: Drug
intervention name: Eicosapentaenoic acid free fatty acid (EPA-FFA)
description: 500mg capsule, two 500mg capsules to be taken twice daily for 24 months
arm group label: Treatment Group A
other name: ALFA
intervention type: Drug
intervention name: Placebo
description: 500mg capsule, two 500mg capsules to be taken twice daily for 24 months
arm group label: Treatment Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Luigi Ricciardiello, MD
role: Principal Investigator
affiliation: Associate Professor of Gastroenterology, University of Bologna
last name: Justin Slagel, CEO
phone: +44 1923 681001
email: info@slapharma.com
facility: 
status: Recruiting
country: Italy
country: Czechia
country: France
country: Israel
country: Netherlands
country: Spain
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Nasopharyngeal Neoplasms
mesh term: Adenomatous Polyposis Coli
sharing ipd: No