Clinical trial NCT06408935: Transmural Healing and Disease-Modifying Effect of Guselkumab in Crohn's Disease Patients
Official title: A Phase 3b, Open-label, Multicenter Study to Evaluate Transmural Healing and Disease Modifying Effect of Guselkumab in Crohn's Disease Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Crohn's Disease
Lead sponsor: Janssen-Cilag Ltd.
Sponsor class: INDUSTRY
First posted: 2024-05-10
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of guselkumab in healing of all layers of the digestive tract (transmural healing) with the help of a score called Magnetic Resonance Index of Activity (MaRIA) based on a scan at Week 48.


Eligibility criteria: Inclusion Criteria:

* Has luminal Crohn's disease (CD) of at least 3 months duration (defined as a minimum of 12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
* Has clinically active CD, defined as a baseline CD activity index (CDAI) score greater than or equal to (\>=)220 but \<=450 and either: a. Mean daily stool frequency (SF) count \>=4, based on the unweighted CDAI component of the number of liquid or very soft stools or b. Mean daily AP score \>=2, based on the unweighted CDAI component of abdominal pain (AP)
* Active transmural activity in at least one segment (segmental magnetic resonance index of activity \[MaRIA\] \>= 11)
* a. Has demonstrated inadequate response/intolerance to conventional therapy; b. Has previously demonstrated lack of initial response (that is, primary non-responders), responded initially but then lost response with continued therapy (that is, secondary non-responders), or was intolerant to a maximum of 1 class of advanced therapies at a dose approved for the treatment of Crohn's disease (that is, janus kinase \[JAK\] inhibitors, infliximab, adalimumab, certolizumab pegol, vedolizumab, ustekinumab, or approved biosimilars for these agents)

Exclusion Criteria:

* Has complications of Crohn's disease, such as symptomatic strictures or stenoses (unless less than \[\<\]3 centimeter (cm) dilatation and not symptomatic or displaying associated fistula/fistulae and/or or abscess), fibrotic stenosis, internal fistulas, short gut syndrome, or any other manifestation, that might be anticipated to require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with guselkumab
* Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks before baseline, or 8 weeks before baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery. Participants with active perianal fistulas may be included if there are no associated stenoses, no anticipated surgery and no abscesses currently identified
* Has had any kind of bowel resection within 6 months, or any other intra-abdominal or other major surgery within 12 weeks before baseline
* Has a draining (that is, functioning) stoma or ostomy
* Has a stool culture or other examination positive for an enteric pathogen, including Clostridioides difficile (formerly known as Clostridium difficile) toxin, in the previous 4 months, unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen

Primary outcomes:
measure: Percentage of Participants Achieving a Magnetic Resonance Index of Activity (MaRIA) Less Than (<)11 in All Intestinal Segments at Week 48
timeFrame: At Week 48
Secondary outcomes:
measure: Percentage of Participants Achieving a MaRIA <11 in All Intestinal Segments at Weeks 16 and 96.
timeFrame: At Weeks 16 and 96
measure: Percentage of Participants Achieving a MaRIA <11 and a Reduction of >=5 Points From Baseline in All Segments at Weeks 16, 48, and 96
timeFrame: At Weeks 16, 48, and 96
measure: Percentage of Participants Achieving a MaRIA <11 in All Segments and Endoscopic Remission at Weeks 48 and 96
timeFrame: At Week 48 and 96
measure: Percentage of Participants Achieving a MaRIA <11 in All Segments and Endoscopic Response at Weeks 48 and 96.
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants Achieving a MaRIA <11 in All Segments, Patient-Reported Outcome-2 (PRO-2) Remission, and No Worsening of Abdominal Pain (AP) or Stool Frequency (SF) From Baseline
timeFrame: At Weeks 16, 48 and 96
measure: Percentage of Participants Achieving a MaRIA <11 in All Segments and Biomarkers Remission
timeFrame: At Weeks 16, 48 and 96
measure: Percentage of Participants Achieving a MaRIA <11 in All Segments, PRO-2, and Endoscopic Remission
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants Achieving a MaRIA <7 in All Intestinal Segments at Weeks 16, 48 and 96
timeFrame: At Weeks 16, 48 and 96
measure: Percentage of Participants Achieving a MaRIA <7 in All Segments and Endoscopic Remission at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Absolute Value of Global Simple MaRIA Score Through Week 96
timeFrame: Baseline up to Week 96
measure: Change From Baseline in the Global Simple MaRIA Score Through Week 96
timeFrame: Up to Week 96
measure: Percentage of Participants Achieving a MaRIA <7 in All Intestinal Segments and Not Receiving Corticosteroids at Weeks 16, 48, and 96
timeFrame: At Weeks 16, 48, and 96
measure: Percentage of Participants Achieving Transmural Segmental Response with Intestinal Ultrasound (IUS) at Weeks 4, 8, 16, 48, and 96
timeFrame: Baseline, at Weeks 4, 8, 16, 48, and 96
measure: Percentage of Participants with Transmural Response (total) at Weeks 4, 8, 16, 48, and Week 96
timeFrame: Baseline, at Weeks 4, 8, 16, 48, and Week 96
measure: Percentage of Participants Achieving Transmural Remission with IUS at Weeks 4, 8, 16, 48, and 96
timeFrame: At Weeks 4, 8, 16, 48, and 96
measure: Absolute Value of International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) Through Week 96
timeFrame: Baseline up to Week 96
measure: Change from Baseline in International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) Through Week 96
timeFrame: Up to Week 96
measure: Percentage of Participants Achieving IBUS-SAS Response at Weeks 4, 8, 16, 48, and Week 96
timeFrame: Baseline, at Weeks 4, 8, 16, 48, and Week 96
measure: Percentage of Participants Achieving BWT <=3 mm for Ileum and Colon Plus CDS 0, in all segments and Participants Not Receiving Corticosteroids at Weeks 4, 8, 16, 48, and 96
timeFrame: At Weeks 4, 8, 16, 48, and 96
measure: Absolute Value of BWT through Week 96
timeFrame: Baseline up to Week 96
measure: Change From Baseline in BWT Through Week 96
timeFrame: Up to Week 96
measure: Absolute Value of Simple IUS Score For CD (SUS-CD) Score Through Week 96
timeFrame: Baseline up to Week 96
measure: Change From Baseline in the SUS-CD Score Through Week 96
timeFrame: Up to Week 96
measure: Percentage of Participants Achieving Endoscopic Response at Weeks 48 and 96
timeFrame: Weeks 48 and 96
measure: Percentage of Participants Achieving Endoscopic Remission at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Absolute Value of SES-CD Total Score Through Week 96
timeFrame: Baseline up to Week 96
measure: Change From Baseline in the SES-CD Total Score Through Week 96
timeFrame: Up to Week 96
measure: Percentage of Participants (Not Receiving Corticosteroids) Achieving Endoscopic Remission at Weeks 48 and 96
timeFrame: Baseline, at Weeks 48 and 96
measure: Percentage of Participants Achieving Endoscopic Healing of the Intestinal Mucosa at Weeks 48 and 96
timeFrame: At Weeks 48 and 96
measure: Percentage of Participants Achieving Crohn's Disease Activity Index (CDAI) <150 at Weeks 4, 8, 16, 48 and 96
timeFrame: At Weeks 4, 8, 16, 48 and 96
measure: Percentage of Participants Achieving a Reduction in the CDAI Score of >=100 points or CDAI <150 From Baseline at Weeks 4, 8, 16, 48, and 96
timeFrame: At Weeks 4, 8, 16, 48, and 96
measure: Percentage of Participants (Not Receiving Corticosteroids) Achieving CDAI Score <150 at Weeks 4, 8, 16, 48 and 96
timeFrame: At Weeks 4, 8, 16, 48 and 96
measure: Absolute Value of CDAI Score Through Week 96
timeFrame: Baseline up to Week 96
measure: Change From Baseline in CDAI Score Through Week 96
timeFrame: Up to Week 96
measure: Percentage of Participants Achieving PRO-2 Remission at Weeks 4, 8, 16, 48, and Week 96
timeFrame: At Weeks 4, 8, 16, 48, and Week 96
measure: Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Weeks 48 and 96
timeFrame: At Week 48 and Week 96
measure: Percentage of Participants Achieving IBDQ Response at Weeks 48 and 96
timeFrame: Baseline, at Weeks 48 and 96
measure: Absolute Value of IBDQ Through Week 96
timeFrame: Baseline up to Week 96
measure: Change From Baseline in IBDQ Score Through Week 96
timeFrame: Up to Week 96
measure: Change from Baseline in Urgency Numeric Rating Scale (UNRS) Through Week 96
timeFrame: Baseline up to Week 96
measure: Percentage of Participants Achieving C-reactive Protein (CRP) Normalization at Weeks 4, 8, 16, 48, and Week 96
timeFrame: Baseline, at Weeks 4, 8, 16, 48, and Week 96
measure: Percentage of Participants Achieving >=50% Improvement of CRP Response From Baseline at Weeks 4, 8, 16, 48, and 96
timeFrame: Baseline, at Weeks 4, 8, 16, 48, and 96
measure: Percentage of Participants Achieving fCal Normalization at Weeks 4, 8, 16, 48, and 96
timeFrame: Baseline, at Weeks 4, 8, 16, 48, and 96
measure: Percentage of Participants Achieving >=50% Improvement of fCal Response From Baseline at Weeks 4, 8, 16, 48, and 96
timeFrame: Baseline, at Weeks 4, 8, 16, 48, and 96
measure: Change From Baseline in CRP and fCal Levels Over Time
timeFrame: Baseline, Weeks 4, 8, 16, 32, 48, and 96
measure: Values of CRP and fCal Levels Over Time
timeFrame: Baseline, Weeks 4, 8, 16, 32, 48, and 96
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TSAEs) Through Week 48
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: The Queen Elizabeth Hospital
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Melbourne
country: Australia
facility: Northern Hospital
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
city: Macae
country: Brazil
facility: Cliged
city: Passo Fundo
country: Brazil
facility: Instituto Mederi de Pesquisa e Saude
city: Porto Alegre
country: Brazil
facility: NPCRS Nucleo de Pesquisa Clinica do Rio Grande do Sul
city: Votuporanga
country: Brazil
facility: INTEGRAL Pesquisa e Ensino
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: London
country: Canada
facility: Western University & London Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Ceske Budejovice
country: Czechia
facility: Nemocnice Ceske Budejovice a s
city: Hradec Kralove
country: Czechia
facility: Hepato-gastroenterologie HK, s.r.o.
city: Praha 9
country: Czechia
facility: ISCARE a.s.
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Berlin
country: Germany
facility: Praxis Für Gastroenteroligie
city: Frankfurt
country: Germany
facility: Universitatsklinikum Frankfurt/ Medizinische Klinik 1
city: Gottingen
country: Germany
facility: Universitatsmedizin Gottingen
city: Halle
country: Germany
facility: BSF Studiengesellschaft
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig Holstein
city: Lüneburg
country: Germany
facility: Staedtisches Klinikum Lueneburg
city: Münster
country: Germany
facility: MVZ Portal 10
city: Pforzheim
country: Germany
facility: Siloah St Trudpert Klinikum
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: The Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Azienda Ospedaliera Policlinico S. Orsola-Malpighi
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Rho
country: Italy
facility: Asst Rhodense - Ospedale Di Rho
city: Roma
country: Italy
facility: Universita Campus Bio-Medico di Roma
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli IRCCS
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
city: Bydgoszcz
country: Poland
facility: NZOZ Centrum Medyczne KERmed
city: Rzeszow
country: Poland
facility: Centrum Medyczne Medyk
city: Torun
country: Poland
facility: GASTROMED Sp. z o.o.
city: Warszawa
country: Poland
facility: WIP Warsaw IBD Point Profesor Kierkus
city: Wroclaw
country: Poland
facility: Melita Medical Sp. z o.o.
city: Wroclaw
country: Poland
facility: Centrum Medyczne Oporow
city: Wroclaw
country: Poland
facility: EuroMediCare Szpital Specjalistyczny z Przychodnia
city: Zamosc
country: Poland
facility: ETG Zamosc
city: Banska Bystrica
country: Slovakia
facility: FNsP F.D.R. Banska Bystrica
city: Bratislava
country: Slovakia
facility: Cliniq s.r.o.
city: Kosice
country: Slovakia
facility: ENDOMED s.r.o
city: Nitra
country: Slovakia
facility: KM Management spol. s r.o.
city: Presov
country: Slovakia
facility: GASTRO I. s.r.o.
city: Alicante
country: Spain
facility: Hosp. Gral. Univ. Dr. Balmis
city: Cordoba
country: Spain
facility: Hosp Reina Sofia
city: Ferrol
country: Spain
facility: Complejo Hosp Univ. de Ferrol
city: Ferrol
country: Spain
facility: Hosp. Univ. de La Paz
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Madrid
country: Spain
facility: Hosp. Univ. Pta. de Hierro Majadahonda
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Vigo
country: Spain
facility: Hosp. Alvaro Cunqueiro
city: Changhua
country: Taiwan
facility: Chang-Hua Christian Hospital
city: New Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Janssen-Cilag Ltd.
name: Janssen Cilag Ltd. Clinical trial
role: STUDY_DIRECTOR
References: