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    Summary
    EudraCT Number:2017-003629-13
    Sponsor's Protocol Code Number:PROFIT
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2017-12-05
    Trial results View 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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2017-003629-13
    A.3Full title of the trial
    A Prospective, randomised placebo controlled feasibility trial of Faecal Microbiotica Transplantation in cirrhosis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A prospective, randomized placebo controlled feasibility trial of faecal microbiota transplantation in cirrhosis.
    A.3.2Name or abbreviated title of the trial where available
    PROFIT
    A.4.1Sponsor's protocol code numberPROFIT
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02862249
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorKing's College London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNIHR
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKing's College London
    B.5.2Functional name of contact pointDr Charlotte Woodhouse
    B.5.3 Address:
    B.5.3.1Street AddressInstitute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeSE5 9RS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number447941692378
    B.5.5Fax number442032993167
    B.5.6E-mailcharlottewoodhouse@nhs.net
    B.Sponsor: 2
    B.1.1Name of SponsorKing's College Hospital NHS Fundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNIHR
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKing's College London
    B.5.2Functional name of contact pointDr Charlotte Woodhouse
    B.5.3 Address:
    B.5.3.1Street AddressInstitute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeSE5 9RS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number447941692378
    B.5.5Fax number442032993107
    B.5.6E-mailcharlottewoodhouse@nhs.net
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameFaecal Microbiota for Transplantation
    D.3.4Pharmaceutical form Gastroenteral liquid
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntraduodenal use (Noncurrent)
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product Yes
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboGastroenteral liquid
    D.8.4Route of administration of the placeboIntraduodenal use (Noncurrent)
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Cirrhosis of the liver
    E.1.1.1Medical condition in easily understood language
    Scarring of the liver
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10024667
    E.1.2Term Liver cirrhosis
    E.1.2System Organ Class 100000004871
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess whether stabilising gut dysbiosis with FMT in patients with advanced cirrhosis is both feasible and safe
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are to provide preliminary
    evidence of efficacy for a larger randomised trial, with the purpose of:
    (i) Choosing the optimal primary outcome, and
    (ii)Estimating the parameters for sample size calculation.
    (a) As measured by an improvement in liver function tests at 90 days.
    (b) The development of complications of cirrhosis such as infection or
    bleeding.
    (c) The development of any infection during the 90-day follow up
    including chest, urine, stool, ascites (fluid accumulating in the abdominal
    cavity)and blood infection.
    (d) Stability of the transplant by comparing the composition of the
    patient's stool on day 7, 30 and day 90 with the donor stool.
    (e) Comparison of the bacterial composition of saliva with the stool at
    baseline, day 7, 30 and day 90 .
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • 18–75 years
    • Confirmed advanced cirrhosis of any aetiology with a MELD score between 10 and 16. The diagnosis of liver cirrhosis will be based on clinical, radiological, or histological criteria.
    • Patients with alcohol-related liver disease must have been abstinent from alcohol for a minimum of 6 weeks.
    • Patients must be deemed to have capacity to consent to study
    E.4Principal exclusion criteria
    • Severe or life-threatening food allergy
    • Pregnancy or breastfeeding
    • Patients treated for active variceal bleeding, infection, bacterial peritonitis, overt hepatic encephalopathy or acute-on-chronic liver failure within the past 14 days.
    • Patients who have received antibiotics in the past 14 days.
    • Active alcohol consumption of >20 grams/day.
    • Has had a previous liver transplant
    • Hepatocellular carcinoma outside of the Milan Criteria (2)
    • A history of prior gastrointestinal resection such as gastric bypass
    • Patient is not expected to survive the duration of the study (90 days).
    • Severe renal impairment (creatinine >150 µmol/L)
    • Inflammatory bowel disease (IBD)
    • Coeliac disease
    • HIV positive
    • Immunosuppression e.g. more than two weeks treatment with corticosteroids within 8 weeks of intervention, active treatment with tacrolimus, mycophenylate, azathioprine

    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoints of the study will be twofold:
    (i) Assessment of the feasibility of FMT
    c. Assess recruitment rates (including palatability of the intervention)
    d. Assess tolerability of FMT e.g reflux rates
    (ii) Assessment of the safety of FMT

    Success Criteria of Primary Endpoints:
    (i) Assessment of the feasibility and tolerability of FMT:
    • >25% consent rate (of all patients screened ~250)
    • >50% fulfil inclusion/exclusion criteria (of all patients consented ~64)
    • >80% randomised patients treated successfully and completing study up to day 90 (out of those randomised ~22)
    • Availability of obtaining sufficient stool donor samples for the study
    • Reflux rates of transplanted material <20% (e.g. foul taste, smell, nausea and vomiting, indigestion)
    • Significant gastrointestinal side effects (including diarrhoea, constipation, abdominal pain, flatulence and bloating) of <20%

    (ii) Assessment of the safety of FMT:
    •Incidence of any transmissable bacterial or viral infection that is deemed to have been acquired from the donor including Clostridium difficile infection.
    •The development of any Serious Adverse Event (SAE), Serious Adverse Reaction (SAR) or Unexpected Serious Adverse Reaction (USAR) that is not pre-specified or is a known consequence of disease progression or complication of cirrhosis as outlined in section 7.2.5.1 that:
     Results in death
     Is life-threatening
     Required hospitalisation or prolongation of existing hospitalisation
     Results in persistent or significant disability or incapacity
     Consists of a congenital anomaly or birth defect
    E.5.1.1Timepoint(s) of evaluation of this end point
    Patients will be assessed prior to the intervention and then again at 7
    days, 30 days and 90 days after the placebo or FMT administration.
    E.5.2Secondary end point(s)
    The secondary objectives of the study are to provide preliminary evidence of efficacy for a larger randomised trial, with the purpose of:
    (i) Choosing the optimal primary outcome, and
    (ii) Estimating the parameters for sample size calculation.
    (a) As measured by an improvement in global liver synthetic function as assessed by the MELD score [a composite score of serum bilirubin, creatinine and INR] at 90 days.
    (b) Development of overt hepatic encephalopathy (grade 1 or more as measured by the Westhaven Criteria).
    (c) The development of organ failure (hypotension requiring inotropic support, respiratory failure requiring ventilator support or the development of acute kidney injury requiring renal replacement therapy) and infection
    (d) The development of any infection during the 90 day follow up including chest, urinary, stool, ascites and blood infection.
    (e) Stability of the transplanted gut microbiome by comparing the % composition of the stool microbiota on day 7, 30 and 90 with the donor microbiome.
    (f) Comparison of the composition of the salivary microbiome
    with the stool microbiome as a surrogate marker of gut dysbiosis at baseline, day 7, day 30 and day 90 .
    Mechanistic Outcome(s):
    (i) Plasma endotoxin and bacterial DNA quantification at 7, 30 and 90 days.
    (ii) Changes in faecal biomarkers (calprotectin, lactoferrin and M2-Pyruvate Kinase) at 7, 30 and 90 days.
    (iii) Changes in leucocyte function including measurement by lipopolysaccharide-induced macrophage tumour necrosis alpha production and immunological markers using flow cytometry (HLA-DR and TLR-4 expression) at 7, 30 and 90 days.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 7, 30 and 90 post FMT/placebo administration
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind Yes
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial 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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 32
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 32
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state32
    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)
    No different from expected normal treatment. The FMT is administered
    once only and is not required on a regular basis will not need to be
    supplied after the trial has ended.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-01-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-31
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-10-17
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