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    Summary
    EudraCT Number:2018-000844-25
    Sponsor's Protocol Code Number:R668-EE-1774
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-12-11
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2018-000844-25
    A.3Full title of the trial
    A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients with Eosinophilic Esophagitis (EoE)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to determine the efficacy and safety of dupilumab in Adult and Adolescent Patients with Eosinophilic Esophagitis (EoE)
    A.4.1Sponsor's protocol code numberR668-EE-1774
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/059/2020
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorRegeneron Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    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 supportRegeneron Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRegeneron Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Address777 Old Saw Mill River Road
    B.5.3.2Town/ cityTarrytown, NY
    B.5.3.3Post code10591
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrials@regeneron.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 Yes
    D.2.1.1.1Trade name Dupixent
    D.2.1.1.2Name of the Marketing Authorisation holdersanofi-aventis groupe
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 namedupilumab
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNdupilumab
    D.3.9.2Current sponsor codeREGN668
    D.3.9.3Other descriptive nameDUPILUMAB
    D.3.9.4EV Substance CodeSUB130625
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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.IMP: 2
    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 Yes
    D.2.1.1.1Trade name Dupixent
    D.2.1.1.2Name of the Marketing Authorisation holdersanofi-aventis groupe
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 namedupilumab
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNdupilumab
    D.3.9.2Current sponsor codeREGN668
    D.3.9.3Other descriptive nameDUPILUMAB
    D.3.9.4EV Substance CodeSUB130625
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Eosinophilic Esophagitis (EoE)
    E.1.1.1Medical condition in easily understood language
    A chronic allergic/immune condition characterized by inflammation of the esophagus
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10064212
    E.1.2Term Eosinophilic oesophagitis
    E.1.2System Organ Class 10017947 - Gastrointestinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objectives of the study by study part are:
    Part A:
    To determine the treatment effect of dupilumab compared with placebo in adult and adolescent
    patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures,
    and to inform/confirm the final sample size determination for Part B.
    Part B:
    To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and
    adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical
    measures.
    Part C:
    To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with
    EoE after up to 52 weeks of treatment as assessed by histological and clinical measures.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are:
    -To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with EoE
    -To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with EoE, using descriptive analyses
    - To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation
    - To demonstrate the efficacy of dupilumab treatment compared to placebo after 24 weeks and 52 weeks of treatment in adult and adolescent patients with EoE who have previously received swallowed topical corticosteroids.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    A substudy of esophageal distensibility utilizing the endolumenal functional lumen imaging probe (EndoFLIP)

    This substudy may be performed at selected North American sites in approximately 150 adult patients, with measurements performed at screening, week 24 and week 52.

    The endpoint of this study is:
    Absolute change from baseline in esophageal distensibility plateau measured by functional lumen imaging, if collected, at week 24.

    Note: this endpoint will also be assessed at week 52 and summarized with descriptive statistics based on the treatment assignment in the double-blind treatment period as well as the extended active treatment assignment for patients previously in the placebo group.

    Genomics Substudy (Optional)

    Blood DNA and RNA samples will be collected for the pharmacogenomics analyses to understand the genetic determinants of efficacy and safety associated with the treatments in this study, and the molecular basis of EoE and related diseases.

    The purpose of the pharmacogenomic analyses is to identify genomic associations with clinical or
    biomarker response to dupilumab, other EoE clinical outcome measures, and possible AEs. In
    addition, associations between genomic variants and prognosis or progression of EoE as well as
    related allergic/atopic diseases may also be studied.
    E.3Principal inclusion criteria
    Key Inclusion Criteria (Parts A & B):
    1. A documented diagnosis of EoE by endoscopic biopsy
    2. Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration
    3. History (by patient report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening.








    NOTE: Other protocol defined inclusion criteria apply.
    E.4Principal exclusion criteria
    Key Exclusion Criteria (Parts A & B):
    1. Body weight ≤40 kg
    2. Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab
    3. Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 6 weeks prior to screening.
    4. Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
    5. Active Helicobacter pylori infection
    6. History of achalasia, Crohn’s disease, ulcerative colitis, celiac disease, and prior esophageal surgery
    7. Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening
    8. History of bleeding disorders or esophageal varices
    9. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study


    NOTE: Other protocol defined exclusion criteria apply.

    Key Exclusion Criteria (Part C):
    1. Participants who, during Part A or Part B, developed a serious adverse event (SAE) and/or adverse event (AE) deemed related to study drug, which in the opinion of the investigator could indicate that continued treatment with study drug may present an unreasonable risk for the participant.
    2. Participants who became pregnant during Part A or Part B
    3. Participants who are prematurely discontinued from study drug due to an AE (patients who are prematurely discontinued from study drug due to lack of efficacy are eligible to enter Part C)
    4. Patients who did not undergo endoscopy with biopsies prior to receiving rescue treatment
    E.5 End points
    E.5.1Primary end point(s)
    The co-primary endpoints of the study are:
    -Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) at week 24
    -Absolute change in Dysphagia Symptom Questionnaire (DSQ) score from baseline to week 24
    E.5.1.1Timepoint(s) of evaluation of this end point
    At week 24. Note: All the above co-primary will be assessed at week 52 as secondary endpoints
    E.5.2Secondary end point(s)
    The key secondary endpoints of the study are:
    -Absolute change in EoE endoscopic reference score (EREFS) from baseline to week 24
    -Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) from
    baseline to week 24
    -Absolute change in EoE Grade Score from the EoE Histology Scoring System (EoEHSS) from baseline to week 24
    -Absolute change in EoE Stage Score from the EoEHSS from baseline to week 24

    The other secondary endpoints are:
    -Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf at week 24
    -Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf at week 24
    -Percent change in DSQ from baseline to week 24
    -Normalized Enrichment Scores (NES) for the relative change from baseline to week 24 in the EoE diagnostic panel (EDP) transcriptome signature
    -NES for the relative change from baseline to week 24 in the type 2 inflammation transcriptome signature
    -Absolute change from baseline to week 24 in health-related QOL as measured by EoE Impact Questionnaire (EoE-IQ)
    -Absolute change from baseline to week 24 in severity and/or frequency of EoE symptoms other than dysphagia
    -Proportion of patients who receive rescue medications or procedures during the 24-week placebo-controlled treatment period
    -Absolute change from baseline in esophageal distensibility plateau measured by functional lumen imaging, if collected, at week 24.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At week 24. Note: All the above co-primary and secondary endpoints assessed at week 24 will be assessed at week 52 as secondary endpoints
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    24-week placebo-controlled treatment period followed by 28-week active treatment period
    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 trial3
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA37
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    United States
    Belgium
    France
    Germany
    Italy
    Netherlands
    Spain
    Sweden
    Switzerland
    United Kingdom
    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 years4
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 82
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 82
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 198
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 127
    F.4.2.2In the whole clinical trial 290
    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
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-12-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-07-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-06-07
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