Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-002697-39
    Sponsor's Protocol Code Number:MPOH03
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-03-15
    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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2017-002697-39
    A.3Full title of the trial
    Treatment of steroid refractory gastro-intestinal acute graft-versus-Host disEase afteR AllogeneiC hematopoietic stem celL transplantation with fEcal microbiota transfer (HERACLES)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Treatment of gastro-intestinal graft vs. host disease with rectal infusion of bacteria in patients not responsive to steroids.
    A.3.2Name or abbreviated title of the trial where available
    HERACLES
    A.4.1Sponsor's protocol code numberMPOH03
    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 SponsorMaaT Pharma
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMaaT Pharma
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMaaT Pharma
    B.5.2Functional name of contact pointDavid Salako, Project Director
    B.5.3 Address:
    B.5.3.1Street Address317 avenue Jean Jaurès
    B.5.3.2Town/ cityLyon
    B.5.3.3Post code69007
    B.5.3.4CountryFrance
    B.5.6E-maildsalako@maat-pharma.com
    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 nameMaaT013
    D.3.2Product code 7P010
    D.3.4Pharmaceutical form Rectal suspension
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPRectal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeMaaT013
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number30 to 90
    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 No
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Steroid refractory gastro-intestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
    E.1.1.1Medical condition in easily understood language
    Medical complication not treatable with steroids following the receipt of transplanted tissue from a genetically different person.
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Evaluation of response (Complete Response (CR) and Very Good Partial Response (VGPR)) of steroid refractory (SR) gastro-intestinal (GI) acute graft-versus-host disease (aGVHD) treated with allogeneic Fecal Microbiota Transfer (FMT).
    E.2.2Secondary objectives of the trial
    Evaluation of safety within 24 hours after FMT in patients with SR-GI-aGVHD, as well as overall safety.

    Other secondary:
    •Evaluation of feasibility of allogeneic FMT procedure and acceptability by the patient
    •Evaluation of clinical safety and performance of MaaT Pharma’s medical device
    •Evaluation of FMT activity and/or impact on:
    -Steroid-free, Progression-free survival, Maintenance of response, Relapse of the initial disease, GVHD free survival, GVHD and Relapse free survival and overall survival at D28 and M6 post inclusion
    -Infectious disorders
    -Multi-Drug Resistant Bacteria (MDRB) carriage
    -Clinical symptoms of skin/ liver aGVHD associated with SR-GI-aGVHD
    -Stool evaluation (Volume of diarrhea, Bristol stool chart)
    •Chronic GVHD expression
    •Evaluation of microbiota reconstitution post FMT
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Patients who develop a first episode of Stage 3 or 4 GI-aGVHD with gut predominance (Przepiorka D, 1995), resistant to a first line therapy with steroids (lack of improvement after 5 days or progression after 3 days of treatment with corticosteroids at 2 mg/Kg methylprednisolone equivalent dose) (SR GI-aGVHD)
    -Age ≥ 18 years old
    -Allo-HSCT with any type of donor, stem cell source, GVHD prophylaxis or conditioning regimen
    -Patients able to have a minimum of 12 hours discontinuation of systemic antibiotics in order to perform the allogeneic FMT (for patient who received antibiotics MaaT Pharma advises against the use of antibiotics (commonly used) with significant digestive excretion (for example but not limited to: metronidazol, ceftriaxone, levofloxacin))
    -Signature of informed and written consent by the subject or by the subject’s legally acceptable representative
    E.4Principal exclusion criteria
    -Grade IV hyper-acute GVHD as defined by the MD Anderson’s criteria (Saliba RM, 2007)
    -Late onset aGVHD as defined by the NIH Consensus Criteria (Jagasia MH, 2015)
    -Overlap chronic GVHD as defined by the NIH Consensus Criteria (Jagasia MH, 2015)
    -Acute GVHD after donor lymphocytes infusion (DLI)
    -Relapsed/persistent malignancy requiring rapid immune suppression withdrawal
    -Active uncontrolled infection according to the attending physician
    -Other systemic drugs than corticosteroids for GVHD treatment (including extra-corporeal photopheresis). Drugs already being used for GVHD prevention (eg. calcineurin inhibitors) are allowed.
    -Absolute neutrophil count <0.5 x 109 /L
    -Absolute platelet count < 10 000
    -Patient EBV negative
    -Evidence of toxic megacolon or gastrointestinal perforation on abdominal X-ray
    -Known allergy or intolerance to trehalose or maltodextrin or latex
    -Pregnancy: positive urinary or blood test in female of childbearing potential; lactation; absence of effective contraceptive method for female of childbearing potential
    -Other ongoing interventional protocol that might interfere with the current study primary endpoint.
    E.5 End points
    E.5.1Primary end point(s)
    1)Efficacy of FMT in the treatment of SR-GI-aGVHD at D28 post inclusion (V4):
    Proportion of patients achieving GI and overall GVHD response by D28, defined as Complete response (CR) or Very Good Partial Response (VGPR)

    Complete response (CR):
    A GVHD CR is defined as follows (Glucksberg) :
    1)GVHD CR is complete resolution of all signs and symptoms of acute GVHD in all organs without intervening salvage.
    2)GI CR is defined as:
    a.Able to eat, not requiring parenteral nutrition, and
    b.Passing primarily formed stools

    Very Good Partial Response (VGPR):
    A GVHD VGPR is defined as follows (Martin PJ B. C., 2009):
    1)Skin: no rash or residual erythematous rash involving < 25% of the body surface, without bullae (residual faint erythema and hyperpigmentation do not count)
    2)Liver: total serum bilirubin concentration < 2 mg/dL or < 25% of baseline at enrollment
    3)Gut: tolerating food or enteral feeding, predominantly formed stools, no overt GI bleeding or abdominal cramping and no more than occasional nausea or vomiting


    E.5.1.1Timepoint(s) of evaluation of this end point
    D28 post inclusion (V4)
    E.5.2Secondary end point(s)
    2)Safety of FMT in patients with SR-GI-aGVHD
    The overall safety of the study will be evaluated with the incidence of all AEs and SAEs (frequency, grade, relationship) throughout the study period
    3)Feasibility of allogeneic FMT procedure and acceptability by the patient
    4)Clinical safety and performance of MaaT Pharma’s medical device (Directive 9342 CE, med dev 2.7.1)

    5)Evaluation of FMT activity and/or impact on Steroid-free, Progression-free survival, Maintenance of response, Relapse of the initial disease, GVHD free survival, GVHD and Relapse free survival and overall survival
    6)Evaluation of FMT activity and/or impact on infectious disorders
    7)Evaluation of FMT activity and/or impact on MDRB carriage
    8)Evaluation of FMT activity and/or impact on clinical symptoms of skin/ liver aGVHD associated with SR-GI-aGVHD
    9)Stool evaluation (volume of diarrhea, Bristol stool chart)
    10)Evaluation of microbiota reconstitution
    11)Chronic GVHD expression
    12)Assessment of a microbiota signature (Exploratory)
    E.5.2.1Timepoint(s) of evaluation of this end point
    D28 post inclusion (V4) and M6 (V5)
    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 Yes
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    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 No
    E.8.2.3Other No
    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.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA21
    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 years0
    E.8.9.1In the Member State concerned months18
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months18
    E.8.9.2In all countries concerned by the trial days0
    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: 25
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 7
    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 No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Subject´s legally acceptable representative may sign the informed and written consent.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state11
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 32
    F.4.2.2In the whole clinical trial 32
    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
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-12-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-30
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-11-26
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 27 00:22:36 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA