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    Summary
    EudraCT Number:2018-004694-27
    Sponsor's Protocol Code Number:IM011024
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-01-25
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-004694-27
    A.3Full title of the trial
    A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of BMS-986165 in Subjects with Moderate to Severe Ulcerative Colitis
    Studio di fase 2, randomizzato, in doppio cieco, controllato con placebo sulla sicurezza e l’efficacia di BMS-986165 in soggetti affetti da colite ulcerosa da moderata a grave
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety and Efficacy of BMS-986165 Compared with Placebo in Subjects with Ulcerative Colitis
    Sicurezza ed efficacia di BMS-986165 in soggetti affetti da colite ulcerosa da moderata a grave
    A.3.2Name or abbreviated title of the trial where available
    na
    na
    A.4.1Sponsor's protocol code numberIM011024
    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 SponsorBRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
    B.1.3.4CountryBelgium
    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 supportBristol Myers-Squibb International Corporation
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBristol-Myers Squibb International Corporation
    B.5.2Functional name of contact pointGCT-SU
    B.5.3 Address:
    B.5.3.1Street AddressParc de l'Alliance - Avenue de Finlande 4
    B.5.3.2Town/ cityBraine-l'Alleud
    B.5.3.3Post code1420
    B.5.3.4CountryBelgium
    B.5.6E-mailclinical.trials@bms.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 nameBMS-986165
    D.3.2Product code [BMS-986165]
    D.3.4Pharmaceutical form Film-coated tablet
    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.3.9.1CAS number 1609392-27-9
    D.3.9.2Current sponsor codeBMS-986165
    D.3.9.4EV Substance CodeSUB180283
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 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 placeboFilm-coated tablet
    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
    Ulcerative Colitis
    Colite ulcerosa
    E.1.1.1Medical condition in easily understood language
    inflammatory bowel disease
    Malattia infiammatoria intestinale
    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 LLT
    E.1.2Classification code 10045365
    E.1.2Term Ulcerative colitis
    E.1.2System Organ Class 100000004856
    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 the effect of BMS-986165 on clinical remission at the end of the induction period
    - To assess the safety and tolerability of BMS-986165 in subjects with moderate to severe UC
    - Valutare l’effetto di BMS-986165 sulla remissione clinica al termine del periodo di induzione
    - Valutare la sicurezza e la tollerabilità di BMS-986165 nei soggetti affetti da CU da moderata a grave
    E.2.2Secondary objectives of the trial
    - To assess the effect of BMS-986165 on clinical response through the end of the induction period
    - To assess the effect of BMS 986165 on endoscopic response at the end of the induction period
    - To assess the effect of BMS-986165 on endoscopic remission at the end of the induction period
    - Valutare l’effetto di BMS-986165 sulla risposta clinica fino al termine del periodo di induzione
    - Valutare l’effetto di BMS-986165 sulla risposta endoscopica al termine del periodo di induzione
    - Valutare l’effetto di BMS-986165 sulla remissione endoscopica al termine del periodo di induzione
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    a) Documented diagnosis (endoscopic and histological) of UC at least 12 weeks prior to screening
    b) Disease severity: moderate to severe active UC defined as an Adapted Mayo Score of 5 to 9 points, inclusive, that includes all of the following subscore values:
    • An endoscopic subscore of >= 2 (screening endoscopy)
    • A rectal bleeding subscore >= 1
    • A stool frequency subscore of >= 2
    c) Active UC extending >= 15 cm from the anal verge and confirmed by a screening/baseline colonoscopy/sigmoidoscopy prior to the randomization visit
    d) Documentation of an inadequate response, loss of response, or intolerance to a treatment course of 1 or more of the following standard of care medications:
    • 5- ASAs, such as mesalamine, sulfasalazine, olsalazine, or balsalazide
    • CS, such as prednisone (or equivalent) or budesonide (or equivalent)
    • Immunosuppressants, such as azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX)
    • Anti-tumor necrosis factor (TNF)-a agents, such as infliximab, adalimumab, or golimumab
    • Integrin inhibitor, such as vedolizumab
    Subjects currently using concomitant salicylates, probiotics, or oral CS (<= 20 mg prednisone or equivalent, <= 9 mg budesonide or equivalent) at stable doses prior to the randomization visit are eligible provided they are on stable doses for the specified time period.
    a) Diagnosi (endoscopica e istologica) documentata di CU da almeno 12 settimane prima dello screening.
    b) Gravità della malattia: CU attiva da moderata a grave, definita come un punteggio Mayo adattato di 5-9 punti, estremi compresi, che include tutti i seguenti valori:
    • un sottopunteggio endoscopico >=2 (endoscopia di screening);
    • un sottopunteggio di sanguinamento rettale (RB) >=1;
    • un sottopunteggio di frequenza delle evacuazioni (SF) >=2.
    c) CU attiva che si estende per >=15 cm dal margine anale e confermata mediante una colonscopia/sigmoidoscopia di screening/basale prima della visita di randomizzazione.
    d) Documentazione di una risposta inadeguata, perdita di risposta o intolleranza a un ciclo di terapia standard oppure 1 o più dei seguenti farmaci previsti dallo standard di cura:
    • acidi 5-aminosalicilici (ASA), quali mesalamina, sulfasalazina, olsalazina o balsalazide;
    • corticosteroidi, quali prednisone (o equivalente) o budesonide (o equivalente);
    • immunosoppressori, quali azatioprina (AZA), 6-mercaptopurina (6-MP) o metotrexato (MTX);
    • agenti anti-fattore di necrosi tumorale (TNF)-a, quali infliximab, adalimumab o golimumab;
    • inibitori dell’integrina, come vedolizumab.
    Soggetti che fanno uso concomitante di salicilati, probiotici e corticosteroidi (CS) orali (<=20 mg di prednisone o equivalente, <=9 mg di budesonide o equivalente) a una dose stabile prima della visita di randomizzazione sono idonei purché siano a una dose stabile per il periodo di tempo specificato.
    E.4Principal exclusion criteria
    • Previous/current documented diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, or pseudomembranous colitis.
    • Positive stool culture for enteric pathogens (ova and parasites, bacteria) or positive for Clostridium difficile (C. difficile) at screening. Subjects who show a C. difficile positive result during screening, may re-screen for the study after they have successfully completed therapy (as per institutional practice) and been resolved for at least 2 weeks prior to the start of rescreening. Investigator will be responsible for clinically assessing eligibility.
    • Current or recent (within 12 weeks prior to the randomization visit) evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation.
    • History or evidence of any extensive colonic resection, subtotal or total colectomy, with or without presence of a stoma or ileoanal pouch. Current need for, or anticipated need for, surgical intervention for UC during the study.
    • History of diverticulitis within 60 days prior to the randomization visit (previous diverticulitis that has been successfully treated with a local standard course of antimicrobial therapy is permitted; however, the course of antimicrobial therapy must be completed at least 30 days prior to the randomization visit).
    • Current colonic adenomas or dysplasia or past confirmed colonic dysplasia that has not been eradicated (subjects who have had UC > 8 years should have had a colonoscopy to screen for dysplasia within 1 year prior to the randomization visit, or this can be performed as part of screening colonoscopy). A subject with prior history of adenomatous polyps will be eligible if the polyps have been completely removed (documented) and the subject is free of polyps at baseline.
    • Prior exposure to treatment with TYK2 inhibitors.
    • Prior lack of response to anti-12/23 p40 antibodies (such as ustekinumab or briakinumab) or anti-IL-23 p19 antibodies (such as guselkumab, risankizumab, tildrakizumab, MEDI2070, LY3074828).
    • Failure or loss of response to janus kinase (JAK) inhibitors, such as tofacitinib.
    • Nonresponders (ie, inadequate response and/or loss of response defined in APPENDIX 5) to > 2 biologic agents (eg, anti-TNF agents or vedolizumab) for the treatment of UC.
    • Use of other investigational agents within 12 weeks or 5 half-lives prior to the randomization visit.
    • Use of topical rectal treatment with 5-ASA or CS within 2 weeks prior to the randomization visit.
    • Current use of CS at a dose of > 20 mg/day for prednisone or equivalent or > 9 mg/day for budesonide or equivalent.
    • Use of immunosuppressants (AZA, 6-MP, or MTX) within 4 weeks prior to the randomization visit.
    • Use of a biologic agent within 8 weeks or 5 half-lives, whichever is longer, prior to the randomization visit
    o Fecal transplant is considered as "investigational” biologic agent and the appropriate washout period must be 8 weeks or 5 half-lives (if known), whichever is longer.
    Please, refer to the Protocol for the full list of exclusion criteria
    • Diagnosi pregressa/attuale documentata di malattia di Crohn, colite indeterminata, colite ischemica o colite pseudomembranosa.
    • Positività della coltura fecale a patogeni enterici (uova e parassiti, batteri) o positività al Clostridium difficile (C. difficile) allo screening. I soggetti che risultano positivi a C. difficile durante lo screening possono essere nuovamente sottoposti allo screening per lo studio dopo aver completato con successo la relativa terapia (secondo le pratiche istituzionali) e a condizione che l’infezione si sia risolta da almeno 2 settimane prima dell’inizio del nuovo screening. Lo sperimentatore avrà la responsabilità di valutare l’idoneità a livello clinico.
    • Evidenza attuale o recente (entro 12 settimane prima della visita di randomizzazione) di colite fulminante, ascessi addominali, megacolon tossico o perforazione intestinale.
    • Anamnesi o evidenza di qualsiasi resezione estensiva del colon, colectomia subtotale o totale, con o senza presenza di una tasca stomatica o ileoanale. Necessità attuale o prevista di un intervento chirurgico per CU durante lo studio.
    • Anamnesi di diverticolite nei 60 giorni precedenti la visita di randomizzazione (è consentita una precedente diverticolite che sia stata trattata con successo mediante un ciclo standard locale di terapia antimicrobica; tuttavia, il ciclo di terapia antimicrobica deve essersi concluso almeno 30 giorni prima della visita di randomizzazione).
    • Adenomi o displasia del colon in corso o precedente displasia del colon confermata che non è stata eradicata (i soggetti che hanno sofferto di CU per >8 anni devono essersi sottoposti a una colonscopia per lo screening della displasia entro 1 anno prima della visita di randomizzazione o, in alternativa, questa può essere eseguita nell’ambito della colonscopia di screening). Un soggetto con anamnesi pregressa di polipi adenomatosi sarà idoneo se i polipi sono stati completamente rimossi (con relativa documentazione) e il soggetto non presenta polipi al basale.
    • Precedente esposizione al trattamento con inibitori di TYK2.
    • Precedente mancata risposta ad anticorpi anti-12/23 p40 (come ustekinumab o briakinumab) o anticorpi anti-IL-23 p19 (come guselkumab, risankizumab, tildrakizumab, MEDI2070, LY3074828).
    • Mancata risposta o perdita di risposta a inibitori della Janus chinasi (JAK), come tofacitinib.
    • Non rispondenti (ovvero, soggetti che mostrano risposta inadeguata e/o perdita di risposta come definito nell’APPENDICE 5) a >2 agenti biologici (es. agenti anti-TNF o vedolizumab) per il trattamento della CU.
    • Uso di altri agenti sperimentali entro 12 settimane o 5 emivite prima della visita di randomizzazione.
    • Uso di trattamenti rettali topici con 5-ASA o CS nelle 2 settimane precedenti la visita di randomizzazione.
    • Uso attuale di CS a una dose >20 mg/giorno di prednisone o equivalente o >9 mg/giorno di budesonide o equivalente.
    • Uso di immunosoppressori (AZA, 6-MP o MTX) nelle 4 settimane precedenti la visita di randomizzazione.
    • Uso di un agente biologico nelle 8 settimane o 5 emivite, a seconda di quale duri di più, prima della visita di randomizzazione.
    o Il trapianto fecale è considerato un agente biologico “sperimentale” e il relativo periodo di washout deve essere di 8 settimane o 5 emivite (se noto), a seconda di quale duri di più.
    Si prega di far riferimento al Protocollo per la lista completa dei criteri di esclusione
    E.5 End points
    E.5.1Primary end point(s)
    Clinical remission per Adapted Mayo Score
    Remissione clinica in base al punteggio Mayo adattato
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12
    Settimana 12
    E.5.2Secondary end point(s)
    • Clinical response
    • Endoscopic response
    • Endoscopic remission
    • Risposta clinica
    • Risposta endoscopica
    • Remissione endoscopica
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 12
    Settimana 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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    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) 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 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) Yes
    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 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 EEA38
    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
    Australia
    Japan
    Korea, Republic of
    Russian Federation
    United States
    Belgium
    Czechia
    Germany
    Hungary
    Italy
    Poland
    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
    End of trial is defined as the last scheduled procedure shown in the Schedule of Activities for the last subject.
    La conclusione della sperimentazione è definita come l'ultima procedura programmata indicata nel Calendario delle attività per l'ultimo soggetto.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years3
    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: 108
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 12
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 76
    F.4.2.2In the whole clinical trial 120
    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)
    At the end of the study, the investigator should ensure that subjects continue to receive appropriate standard of care to treat the condition under study. In addition, for subjects who continue to demonstrate clinical benefit, BMS may continue to provide study treatment via an extension of the current study, a rollover study requiring approval by the responsible health authority and ethics committee, or through another mechanism at the discretion of BMS.
    Al termine dello studio, lo sperimentatore deve assicurarsi che il soggetto continui a ricevere le cure di base adeguate per il trattamento della patologia di studio. Inoltre, per i pazienti che continuano a dimostrare benfici clinici, BMS può continuare a fornire il trattamento di studio attraverso un estensione dello studio attuale, uno studio di rollover richiede l'approvazione dell'autorità sanitaria di competenza e del comitato etico, o attraverso un altro meccanismo, a discrezione di BMS
    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 Decision2019-08-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-07-16
    P. End of Trial
    P.End of Trial StatusOngoing
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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
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