A Phase 3b, Open-label, Multicenter Study to Evaluate Transmural Healing and Disease Modifying Effect of Guselkumab in Crohn's Disease Patients

Official 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 Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 120 participants

Study Arms

• Guselkumab (EXPERIMENTAL)
  Participants will receive guselkumab 200 milligram (mg) intravenously (IV) at week 0, 4 and 8. Afterwards, participants will be alternately assigned at study level to 2 dose cohorts, high dose (200 mg subcutaneous (SC) every 4 weeks (Q4W) starting at week 12) through week 92 or low dose (100 mg SC every 8 weeks (Q8W) starting at week 16) through week 88. Starting at Week 24, participants in the low-dose cohort will be permitted to escalate to the 200 mg SC Q4W regimen if they are symptomatic and

Interventions

• DRUG: Guselkumab — Guselkumab will be administered IV and SC.

Primary Outcomes

• Percentage of Participants Achieving a Magnetic Resonance Index of Activity (MaRIA) Less Than (<)11 in All Intestinal Segments at Week 48 (At Week 48)

Secondary Outcomes

• Percentage of Participants Achieving a MaRIA <11 in All Intestinal Segments at Weeks 16 and 96. (At Weeks 16 and 96)
• Percentage of Participants Achieving a MaRIA <11 and a Reduction of >=5 Points From Baseline in All Segments at Weeks 16, 48, and 96 (At Weeks 16, 48, and 96)
• Percentage of Participants Achieving a MaRIA <11 in All Segments and Endoscopic Remission at Weeks 48 and 96 (At Week 48 and 96)
• Percentage of Participants Achieving a MaRIA <11 in All Segments and Endoscopic Response at Weeks 48 and 96. (At Weeks 48 and 96)
• 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 (At Weeks 16, 48 and 96)

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

Trial Locations

• Center for Colitis and Crohns Disease University of California, San Francisco, California, United States
• The University of Chicago Medical Center (UCMC), Chicago, Illinois, United States
• Washington University School Of Medicine, St Louis, Missouri, United States
• Medical University of South Carolina, Charleston, South Carolina, United States
• The Queen Elizabeth Hospital, Adelaide, Australia
• Concord Repatriation General Hospital, Concord, Australia
• Northern Hospital, Melbourne, Australia
• Fiona Stanley Hospital, Murdoch, Australia
• Mater Hospital Brisbane, South Brisbane, Australia
• AZ Maria Middelares, Ghent, Belgium
• ...and 10 more locations

Study Officials

• Janssen Cilag Ltd. Clinical trial — STUDY_DIRECTOR
  Janssen-Cilag Ltd.

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