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    Summary
    EudraCT Number:2020-000048-73
    Sponsor's Protocol Code Number:AMT-101-201
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-08-31
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2020-000048-73
    A.3Full title of the trial
    A Combined Phase 2/3 12-week, Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy of AMT-101 in Subjects with Chronic Antibiotic-resistant Pouchitis
    Studio combinato di fase 2/3 della durata di 12 settimane,randomizzato, in doppio cieco, controllato con placebo volto avalutare l’efficacia di AMT-101 in soggetti con pouchite cronica refrattaria agli antibiotici
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of AMT-101 in patients with Pouchitis.
    Studio di AMT-101 in pazienti con pouchite.
    A.3.2Name or abbreviated title of the trial where available
    AMT-101-201
    AMT-101-201
    A.4.1Sponsor's protocol code numberAMT-101-201
    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 SponsorApplied Molecular Transport 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 supportApplied Molecular Transport Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationApplied Molecular Transport Inc.
    B.5.2Functional name of contact pointClinical Trial AMT-101-201
    B.5.3 Address:
    B.5.3.1Street Address1 Tower Place, Suite 850
    B.5.3.2Town/ citySouth San Francisco
    B.5.3.3Post codeCA 94080
    B.5.3.4CountryUnited States
    B.5.4Telephone number16503920420
    B.5.5Fax number16503920420
    B.5.6E-mailCT101@appliedmt.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 nameAMT-101
    D.3.2Product code [AMT-101]
    D.3.4Pharmaceutical form Gastro-resistant capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeAMT-101
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 Yes
    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 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 nameAMT-101
    D.3.2Product code [AMT-101]
    D.3.4Pharmaceutical form Gastro-resistant capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeAMT-101
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 Yes
    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 placeboGastro-resistant capsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pouchitis
    Pouchite
    E.1.1.1Medical condition in easily understood language
    Inflammation of the ileal pouch - an artificial rectum surgically created out of ileal gut tissue in patients who have undergone a colectomy.
    Infiammazione della pouch ileale - un retto artificiale creata chirurgicamente dal tessuto intestinale ileale in pazienti che hanno subito una colectomia.
    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 PT
    E.1.2Classification code 10036463
    E.1.2Term Pouchitis
    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
    Phase 2 Study Objective:
    - To assess the safety, tolerability, systemic exposure, and efficacy of AMT-101 in subjects with chronic antibiotic-resistant pouchitis
    - To select an AMT-101 dose for Phase 3

    Phase 3 Study Co-primary Objectives:
    - To determine the effect of AMT-101 on stool frequency in subjects with chronic antibiotic-resistant pouchitis
    - To determine the effect of AMT-101 on histologic disease activity in subjects with chronic antibiotic-resistant pouchitis
    Fase 2 - Obiettivi dello studio:
    - Valutare la sicurezza, la tollerabilità, l’esposizione sistemica e l’efficacia di AMT- 101 in soggetti con pouchite cronica refrattaria agli antibiotici
    - Selezionare una dose di AMT-101 per la fase 3

    Obiettivi coprimari:
    - Determinare l’effetto di AMT-101 sulla frequenza di evacuazione in soggetti con pouchite cronica refrattaria agli antibiotici
    - Determinare l’effetto di AMT-101 sull’attività istologica di malattia in soggetti con pouchite cronica refrattaria agli antibiotici
    E.2.2Secondary objectives of the trial
    Phase 3 Study Objectives:
    - To assess the efficacy of AMT-101 on histologic, endoscopic, and other clinical signs and symptoms in subjects with chronic antibiotic-resistant pouchitis
    - To assess the safety and tolerability of AMT-101 in chronic antibiotic-resistant pouchitis
    - To assess the efficacy of AMT-101 to improve health-related quality of life (HRQOL)
    - To determine the systemic exposure of subjects following dosing
    Exploratory Objectives (both Phases):
    - To assess the effect of AMT-101 to reduce time to rescue therapy
    - To assess the pharmacodynamic (PD) effect of AMT-101 on endoscopic and histologic inflammation
    - To determine the mucosal tissue exposure of subjects following dosing
    - To assess the PD effect of AMT-101 on change in biomarkers
    - To assess target engagement and mechanism of action
    Phase 3 Obiettivi secondari:
    - Valutare l’efficacia di AMT-101 sugli esiti istologici ed endoscopici e su altri segni e sintomi clinici in soggetti con pouchite cronica refrattaria agli antibiotici
    - Valutare la sicurezza e la tollerabilità di AMT-101 nel trattamento della pouchite cronica refrattaria agli antibiotici
    - Valutare l’efficacia di AMT-101 nel migliorare la qualità della vita correlata alla salute (HRQOL)
    - Determinare l’esposizione sistemica dei soggetti dopo la somministrazione
    Obiettivi esplorativi (entrambe le fasi):
    -Valutare l’effetto di AMT-101 in termini di riduzione del tempo alla terapia di Soccorso
    -Valutare l’effetto farmacodinamico (PD) di AMT-101 sull’infiammazione endoscopica e istologica
    -Determinare l’esposizione dei soggetti a livello di tessuto mucoso dopo la somministrazione
    -Valutare l’effetto PD di AMT-101 sulle variazioni nei biomarcatori
    -Valutare l’interazione farmaco-recettore (target engagement) e il meccanismo d’azione
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male and female subjects aged 18 to 75 yrs, inclusive.
    2. IPAA for UC completed at least 1 yr prior to screening.
    3. Active signs and symptoms of pouchitis, as follows:
    a. Modified Pouchitis Disease Activity Index (mPDAI) score = 5, and,
    b. Increased stool frequency, defined as 3 more stools per day above “normal” (after IPAA) and an absolute total of = 6 stools per day.
    4. Chronic or recurrent pouchitis, defined by:
    a. = 2 episodes within 1 year prior to or including the screening period treated with antibiotic or other prescription therapy, or,
    b. Maintenance antibiotic therapy taken continuously for =4 weeks immediately prior to the screening endoscopy.
    5. Antibiotic-resistant pouchitis, defined as disease remaining active despite at least 2 weeks of antibiotic therapy.
    6. Histologic inflammation in the pouch, defined by a Geboes score of 3.1 or greater.
    7. Unlikley to conceive.
    8. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and at the randomization visit prior to the first dose of study drug.
    9. Able to participate fully in all aspects of this clinical trial.
    10. Written informed consent must be obtained and fully documented.
    11. HIV test must be negative prior to the first dose of study drug.
    1. Soggetti di sesso maschile e femminile di età compresa tra 18 e 75 anni compiuti.
    2. IPAA per CU completata almeno 1 anno prima dello screening.
    3. Segni e sintomi attivi di pouchite, come specificato di seguito:
    a. punteggio dell’Indice modificato di attività della malattia per la pouchite (mPDAI) =5; e
    b. aumento della frequenza di evacuazione, definito come 3 evacuazioni in più al giorno rispetto al “normale” (dopo IPAA) e numero totale assoluto di evacuazioni =6 al giorno.
    4. Pouchite cronica o ricorrente, definita da:
    a. =2 episodi entro 1 anno prima o incluso il periodo di screening trattati con terapia antibiotica o altra terapia su prescrizione; oppure
    b. terapia antibiotica di mantenimento assunta in modo continuativo per =4 settimane subito prima dell’endoscopia di screening.
    5. Pouchite refrattaria agli antibiotici, definita come malattia persistentemente attiva malgrado almeno 2 settimane di terapia antibiotica.
    6. Infiammazione istologica della pouch, definita da un punteggio di Geboes pari o superiore a 3,1.
    7. Improbabilità di concepimento.
    8. Le donne in età fertile (WOCBP) devono risultare negative al test di gravidanza eseguito allo screening e alla visita di randomizzazione prima della prima dose di farmaco dello studio.
    9. Capacità di partecipare pienamente a tutti gli aspetti della sperimentazione clinica.
    10. Acquisizione debitamente documentata di consenso informato scritto.
    11. Il test per l’HIV deve risultare negativo prima di assumere la prima dose del farmaco dello studio.
    E.4Principal exclusion criteria
    1. Known Crohn’s disease (CD) or suspected CD of the pouch, defined as complex perianal/pouch fistula and/or extensive length of pre-pouch ileitis with deep ulceration.
    2. Diagnosed or suspected irritable pouch syndrome (IPS).
    3. Isolated or predominant cuffitis.
    4. Mechanical complications of the pouch such as stricture or fistula(e) that preclude evaluation of the pouch and terminal ileum.
    5. Fecal incontinence due to anal sphincter dysfunction.
    6. Pelvic sepsis within 12 months prior to screening.
    7. Planned surgery for UC, or any other elective surgery within the time frame of the study.
    8. Diverting stoma.
    9. Current bacterial or parasitic pathogenic enteric infection, including Clostridium difficile; known infection with hepatitis B or C virus; known infection with HIV; infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 6 months prior to screening; any infection requiring antimicrobial therapy within 2 weeks prior to screening; history of more than 1 episode of herpes zoster or any episode of disseminated zoster.
    10. A positive diagnostic tuberculosis (TB) test at screening (defined as a positive QuantiFERON test).
    11. Prior biologic use restrictions and exclusions:
    a. No more than 25% of enrolled subjects (in each phase) may have prior failure of any biologics for pouchitis.
    b. Subjects who have used prior biologic therapies must have discontinued within 12 weeks or 5 half-lives of screening (or within 4 weeks if drug levels are undetectable).
    12. Use of any of the following prohibited therapies, except under the stated conditions (if applicable):
    a. Opioids within 4 weeks prior to screening.
    b. Chronic use (>4 weeks of continuous use prior to screening) of nonsteroidal anti-inflammatory drugs, except for chronic use of low-dose 81 mg aspirin.
    c. Oral 5-aminosalicylate (5-ASA), unless the dose is = 4.8 g/day and has been stable for at least 4 weeks prior to screening.
    d. Oral budesonide within 6 weeks of screening.
    e. Other oral corticosteroids at daily doses > 20 mg prednisone or equivalent, or who started oral corticosteroids within 6 weeks prior to screening; stable doses = 20 mg prednisone or equivalent for at least 4 weeks prior to screening are permitted.
    f. Any rectal compounds.
    g. Immunosuppresant therapy (azathioprine, 6-mercaptopurine, methotrexate, cyclosporin) within 8 weeks prior to screening.
    h. Fecal transplant within 12 weeks prior to screening.
    i. Live virus vaccination within 1 month prior to screening.
    j. Any investigational therapy within 4 weeks prior to screening.
    13. Diagnosed with any immune deficiency.
    14. History of malignancy, except for basal cell carcinoma, nonmetastatic squamous cell carcinoma of the skin, or prior malignancy with curative therapy completed at least 5 years prior to screening and no recurrence.
    15. Clinically meaningful laboratory abnormalities at screening that would affect subject safety, as judged by the investigator from local testing.
    16. A concurrent, clinically significant, serious, unstable, or uncontrolled underlying cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitoruinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, might confound study results, pose additional risk to the subject, or interfere with the subject’s ability to participate fully in the study.
    1. Nota o sospetta malattia di Crohn (MC) della pouch, definita come fistola complessa pouch/perianale e/o estesa ileite pre-pouch con ulcerazione profonda.
    2. Diagnosi o sospetto di sindrome della pouch irritabile (IPS).
    3. Cuffite isolata o prevalente.
    4. Complicanze meccaniche della pouch, quali stenosi o fistola/e che impediscono la valutazione della pouch e dell’ileo terminale.
    5. Incontinenza fecale dovuta a disfunzione dello sfintere anale.
    6. Sepsi pelvica entro 12 mesi prima dello screening.
    7. Intervento chirurgico programmato per CU, o qualsiasi altro intervento chirurgico elettivo durante il periodo di svolgimento dello studio.
    8. Stomia di diversione.
    9. Infezione enterica da patogeni batterici o parassitari in atto, incluso Clostridium difficile; infezione nota da virus dell’epatite B o C; infezione nota da HIV; infezione con necessità di ricovero o terapia antimicrobica endovenosa oppure infezione opportunistica entro 6 mesi prima dello screening; qualsiasi infezione che richieda una terapia antimicrobica entro 2 settimane prima dello screening; anamnesi di più di 1 episodio di herpes zoster o qualsiasi episodio di zoster disseminato.
    10. Positività di un test diagnostico per la tubercolosi (TB) allo screening (definita come esito positivo del test QuantiFERON).
    11. Restrizioni ed esclusioni relative all’uso pregresso di agenti biologici:
    a. non più del 25% dei soggetti arruolati (in ciascuna fase) può aver fallito un
    precedente trattamento con agenti biologici per pouchite;
    b. i soggetti precedentemente trattati con terapie biologiche devono aver interrotto il trattamento entro 12 settimane o 5 emivite dallo screening (o entro 4 settimane in caso di livelli di farmaco non rilevabili).
    12. Uso di una qualsiasi delle seguenti terapie vietate, salvo che nelle condizioni indicate (se pertinente):
    a. oppioidi entro 4 settimane prima dello screening;
    b. uso cronico (>4 settimane di uso continuativo prima dello screening) di farmaci antinfiammatori non steroidei, fatta eccezione per l’uso cronico di
    aspirina a bassa dose (81 mg);
    c. acido 5-aminosalicilico (5-ASA) orale, a meno di una dose =4,8 g/giorno e
    rimasta stabile per almeno 4 settimane prima dello screening;
    d. budesonide orale entro 6 settimane dallo screening;
    e. altri corticosteroidi per via orale a dosi giornaliere >20 mg di prednisone o
    equivalente, o iniziati entro 6 settimane prima dello screening; dosi stabili =20 mg di prednisone o equivalente per almeno 4 settimane prima dello screening sono ammesse;
    f. qualsiasi composto per via rettale;
    g. terapia immunosoppressiva (azatioprina, 6-mercaptopurina, metotrexato, ciclosporina) entro 8 settimane prima dello screening;
    h. trapianto fecale entro 12 settimane prima dello screening;
    i. vaccinazione con virus vivo entro 1 mese prima dello screening;
    j. qualsiasi terapia sperimentale entro 4 settimane prima dello screening.
    13. Diagnosi di qualsiasi forma di immunodeficienza.
    14. Anamnesi di tumore maligno, eccetto carcinoma basocellulare, carcinoma squamocellulare della cute non metastatico o pregresso tumore maligno con
    terapia curativa completata almeno 5 anni prima dello screening e assenza di recidiva.
    15. Anomalie di laboratorio clinicamente significative presenti allo screening e in grado di incidere sulla sicurezza del soggetto, come giudicato dallo sperimentatore in base agli esami eseguiti localmente.
    16. Presenza concomitante di una patologia di base clinicamente significativa, grave, instabile o non controllata, di natura cardiovascolare, polmonare, epatica, renale, gastrointestinale, genitourinaria, ematologica, coagulativa, immunologica, endocrina/metabolica o altra patologia medica che, a giudizio dello sperimentatore, potrebbe confondere i risultati dello studio, comportare ulteriori rischi per il soggetto oppure interferire con la capacità del soggetto di partecipare pienamente allo studio.
    E.5 End points
    E.5.1Primary end point(s)
    Co-primary Efficacy Endpoints:
    - Proportion of subjects with a stool frequency response at Week 12; defined as a reduction of = 3 stools AND = 30% reduction in number of stools from baseline, OR back to postoperative baseline number of stools
    - Proportion of subjects with histologic healing at Week 12; defined as neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue (Geboes score < 3.1)
    Endpoint di efficacia co-primari:
    • Percentuale di soggetti che raggiunge una risposta in termini di frequenza di
    evacuazione alla Settimana 12, definita come riduzione di =3 evacuazioni E
    riduzione =30% nel numero di evacuazioni rispetto al basale OPPURE ritorno al
    numero postoperatorio basale di evacuazioni
    • Percentuale di soggetti che raggiunge la guarigione istologica alla Settimana 12,
    definita come infiltrazione neutrofila in <5% delle cripte, assenza di distruzione
    delle cripte e assenza
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12
    Settimana 12
    E.5.2Secondary end point(s)
    Ranked efficacy endpoints:
    1. Proportion of subjects with histologic response at Week 12; defined as a reduction in Pouchitis Disease Activity Index (PDAI) histology subscore = 2 points from baseline or a PDAI histology subscore of 0
    2. Proportion of subjects with minimal histologic activity at Week 12; defined as PDAI neutrophil score = 1 and ulcer score of 0
    3. Mean change in PDAI histologic subscore at Week 12
    4. Proportion of subjects with 50% reduction in Simple Endoscopic Score for Crohn’s Disease (SES-CD) score at Week 12 (area within 1 cm of the pouch suture line will not be included in the endoscopic evaluation)
    5. Mean change in PDAI endoscopic subscore at Week 12
    6. Proportion of subjects achieving mPDAI < 5 and a reduction of overall score by = 2 points from baseline at Week 12
    7. Proportion of subjects achieving PDAI < 7 and a reduction of overall score by = 3 points from baseline at Week 12
    8. Proportion of subjects achieving a partial response at Week 12; defined as reduction of mPDAI score by = 2 points from baseline
    9. Mean change in stool frequency at Weeks 2, 6, 8, 10, 12, and 4WPT
    10. Proportion of subjects with Mayo stool frequency score of 0 or 1 at Weeks 2, 6, 8, 10, 12, and 4WPT
    11. Mean change in urgency score at Week 12 and 4WPT
    12. Mean change in incontinence score (St. Mark’s) at Week 12 and 4WPT
    13. Mean change in rectal bleeding score at Weeks 2, 6, 8, 10, 12, and 4WPT
    14. Mean change in total PDAI score at Week 12

    Safety, HRQOL, and pharmacokinetic (PK) endpoints:
    • Proportion of subjects with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuation due to TEAEs
    • Assessment of laboratory parameters
    • Assessment of vital signs
    • Mean change in Inflammatory Bowel Disease Questionnaire (IBDQ), 5-dimension EuroQoL questionnaire (EQ-5D), and 36-item Short-Form questionnaire (SF-36) at Week 12 and 4WPT
    • Concentration of AMT-101, AMT-101 antidrug antibodies (ADAs), and total interleukin-10 (IL-10) in serum at Week 12

    Exploratory efficacy endpoints:
    • Time to relapse of pouchitis symptoms
    • Time to first use of rescue therapy
    • Increased use of antidiarrheals
    • Proportion of subjects with endoscopic remission; defined as absence of friability and ulceration, represented by a Mayo Endoscopic Subscore (MES) < 1 (area within 1 cm of the pouch suture line will not be included in the endoscopic evaluation)
    • Proportion of subjects with endoscopic remission; defined as a SES-CD score of = 2 (area within 1 cm of the pouch suture line will not be included in the endoscopic evaluation)
    • Change in Robarts Histopathology Index (RHI) score
    • Proportion of subjects who achieve a 50% reduction in RHI

    Exploratory PK/PD endpoints:
    • Concentration of AMT-101, AMT-101 ADAs, and total IL-10 in mucosal tissue biopsies
    • Change in high-sensitivity C-reactive protein (hs-CRP)
    • Change in fecal calprotectin
    • Change in white blood cell (WBC) count
    • Change in fecal matrix metallopeptidase-9 (MMP-9)
    • Change in fecal lactoferrin
    • Change in interleukin-1 receptor antagonist (IL-1Ra)
    • Change in serum and mucosal tissue protein levels
    Endpoint di efficacia ordinati per rango:
    1. Percentuale di soggetti che raggiunge la risposta istologica alla Settimana 12, definita come riduzione nel sottopunteggio istologico dell’Indice di attività della malattia per la pouchite (PDAI) =2 punti rispetto al basale o sottopunteggio istologico dell’Indice PDAI pari a 0
    2. Percentuale di soggetti con attività istologica minima alla Settimana 12, definita come punteggio dei neutrofili secondo l’Indice PDAI =1 e punteggio di ulcerazione pari a 0
    3. Variazione media nel sottopunteggio istologico dell’Indice PDAI alla Settimana 12
    4. Percentuale di soggetti con riduzione del 50% nel punteggio endoscopico semplice per la malattia di Crohn (SES-CD) alla Settimana 12 (l’area compresa entro 1 cm dalla linea di sutura della pouch non sarà inclusa nella valutazione endoscopica)
    5. Variazione media nel sottopunteggio endoscopico dell’Indice PDAI alla Settimana 12
    6. Percentuale di soggetti che raggiunge un punteggio mPDAI <5 e una riduzione del punteggio complessivo di =2 punti rispetto al basale alla Settimana 12
    7. Percentuale di soggetti che raggiunge un punteggio PDAI <7 e una riduzione del punteggio complessivo di =3 punti rispetto al basale alla Settimana 12
    8. Percentuale di soggetti che raggiunge una risposta parziale alla Settimana 12, definita come riduzione del punteggio mPDAI di =2 punti rispetto al basale
    9. Variazione media nella frequenza di evacuazione alle Settimane 2, 6, 8, 10 e 12 e
    4 settimane dopo il trattamento (4WPT)
    10. Percentuale di soggetti con punteggio della frequenza di evacuazione secondo Mayo pari a 0 o 1 alle Settimane 2, 6, 8, 10 e 12 e 4WPT
    11. Variazione media nel punteggio di urgenza alla Settimana 12 e 4WPT
    12. Variazione media nel punteggio di incontinenza (sistema di St. Mark) alla Settimana 12 e 4WPT
    13. Variazione media nel punteggio di sanguinamento rettale alle Settimane 2, 6, 8,
    10, 12 e 4WPT
    14. Variazione media nel punteggio PDAI totale alla Settimana 12
    Endpoint di sicurezza, HRQOL e farmacocinetica (PK):
    • Percentuale di soggetti con eventi avversi emergenti dal trattamento (TEAE), eventi avversi gravi (SAE) e interruzioni dovute a TEAE
    • Valutazione dei parametri di laboratorio
    • Valutazione dei segni vitali
    • Variazione media nel Questionario sulla malattia infiammatoria intestinale (IBDQ), nel Questionario EuroQoL a 5 dimensioni (EQ-5D) e nel Modulo breve a 36 voci (SF-36) alla Settimana 12 e 4WPT
    • Concentrazione di AMT-101, anticorpi anti-farmaco (ADA) anti-AMT-101 e interleuchina-10 (IL-10) totale nel siero alla Settimana 12
    Endpoint esplorativi di efficacia:
    • Tempo alla recidiva dei sintomi di pouchite
    • Tempo al primo utilizzo di una terapia di soccorso
    • Aumento dell’uso di antidiarroici
    • Percentuale di soggetti con remissione endoscopica, definita come assenza di friabilità e ulcerazione, rappresentata da un sottopunteggio endoscopico Mayo (MES) <1 (l’area compresa entro 1 cm dalla linea di sutura della pouch non sarà inclusa nella valutazione endoscopica)
    • Percentuale di soggetti con remissione endoscopica, definita come punteggio SESCD =2 (l’area compresa entro 1 cm dalla linea di sutura della pouch non sarà inclusa nella valutazione endoscopica)
    • Variazione nel punteggio dell’Indice istopatologico di Robarts (RHI)
    • Percentuale di soggetti che raggiunge una riduzione del 50% nel punteggio RHI
    Endpoint esplorativi di PK/PD:
    • Concentrazione di AMT-101, ADA anti-AMT-101 e IL-10 totale nelle biopsie di
    tessuto mucoso
    • Variazione nei livelli di proteina C-reattiva ad alta sensibilità (hs-CRP)
    • Variazione nei livelli di calprotectina fecale
    • Variazione nella conta dei globuli bianchi (GB)
    • Variazione nei livelli di metallopeptidasi-9 di matrice (MMP-9) fecale
    • Variazione nei livelli di lattoferrina fecale
    • Variazione nei livelli dell’antagonista del recettore per l’interleuchina-1 (IL-1Ra)
    • Variazione nei livelli proteici nel siero e nel tessuto mucoso
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 2, 6, 8, 10 and 12
    Settimane 2, 6, 8, 10 e 12
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) 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 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 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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    Belgium
    France
    Germany
    Hungary
    Italy
    Netherlands
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    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: 124
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 108
    F.4.2.2In the whole clinical trial 144
    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)
    Once clinical trial participants have completed the 4 week follow-up visit, the participants will no longer receive study drug. The study doctor will talk to them about how best to continue their medical care.
    Una volta che i partecipanti dello studio hanno completato la visita di follow-up di 4 settimane, i partecipanti non riceveranno più il farmaco in studio. Il medico dello studio parlerà loro del modo migliore per continuare le loro cure mediche.
    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 Decision2021-09-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-18
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2023-04-21
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    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.

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