A Study of Guselkumab for the Treatment of Participants With Crohn's Disease After Surgical Resection
- Registration Number
- NCT05784129
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the effectiveness of guselkumab treatment compared with placebo (an inactive substance with no medicine) in preventing recurrence of Crohn's disease in participants after surgery.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
- Have a documented diagnosis of Crohn's disease (CD) confirmed by endoscopic, histologic, and/or radiologic studies prior to resection or by tissue obtained at resection
- Have undergone an ileocolonic surgical resection (that is, an intestinal resection with an ileocolonic anastomosis) for CD prior to the baseline visit with the following criteria: (a)Have no known active CD anywhere in the gastrointestinal (GI) tract, including the findings at surgery. (b)Be able to undergo randomization no later than 49 days after surgery, and at least 10 days after surgery (or 8 days after resumption of bowel activity, example, in case of postoperative ileus) (c) Ileocolonic resection was not for the purpose of removing known dysplasia. (d) If ileocolonic resection is the participant's first resection for Crohn's, and occurs greater than (>) 10 years since the diagnosis of CD and only fibrostenotic stricturing is present, then length of stricture must be > 10 centimeter (cm)
- Have a baseline Crohn's Disease Activity Index (CDAI) less than (<) 200
- A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) test result during screening and a negative urine pregnancy test at week 0, prior to randomization
- A woman must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 12 weeks after the last administration of study intervention
- Has complications of CD, such as symptomatic strictures or stenoses, short bowel syndrome, a draining (that is, functioning) stoma or ostomy, 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
- Have had any active perianal disease within 3 months of screening (except skin tags) or have had any draining fistula within 3 months of screening unless the fistula was removed at the index surgery
- Evidence of a herpes zoster infection within 8 weeks before the first dose of study intervention
- Has a history of severe, progressive, or uncontrolled renal, genitourinary, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: Guselkumab Guselkumab Participants will receive Guselkumab Dose 1 subcutaneously (SC) followed by Dose 2 SC thereafter through Week 144. Participants with disease recurrence will receive guselkumab SC treatment. Group 2: Placebo Placebo Participants will receive matching placebo injections subcutaneously. Participants with disease recurrence will receive guselkumab SC treatment.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Endoscopic Recurrence Prior to or at Week 48 Baseline (Day 1) up to Week 48 Endoscopic recurrence was defined by modified Rutgeerts score greater than or equal to (\>=) i2a in neo-terminal ileum, anastomotic site, or its equivalent in gastrointestinal (GI) tract (e.g., colonic ulceration). The modified Rutgeerts score ranged from i0 to i4, where i0 (No lesions), i1 (less than \[\<\] 5 aphthous lesions), i2 (greater than \[\>\] 5 aphthous lesions with normal mucosa between lesions or skip areas of larger lesions or lesions confined to ileocolonic anastomosis \[\<1 centimeter (cm) in length\]), i2a (lesions confined to ileocolonic anastomosis \[including anastomotic stenosis\]), i2b (more than 5 aphthous ulcers or larger lesions, with normal mucosa in-between, in the neoterminal ileum \[with or without anastomotic lesions\]), i3 (diffuse aphthous ileitis with diffusely inflamed mucosa), i4 (large ulcers with diffuse mucosal inflammation or nodules or stenosis in neoterminal ileum). Higher score indicated worsening.
- Secondary Outcome Measures
Name Time Method Time To Recurrence of Symptoms Baseline (Day 1) up to Week 48 Time-to-recurrence of symptoms was defined as time to attaining an AP mean daily score \>1 (and also \>1 point higher than baseline) along with stool frequency (SF) mean daily score \>3 (and also \>3 higher per day than baseline) for 2 consecutive weeks through Week 48. AP score scaling was done on a 4-point score scale, ranged from 0 to 3, where 0 equals none, 1 equals mild, 2 equals moderate and 3 equals severe pain. Higher score indicated severe pain. Stool frequency score was calculated from the total number of liquid or very soft stools in the previous 7 days.
Percentage of Participants With Clinical Remission Without Disease Recurrence at Week 48 At Week 48 Clinical remission without disease recurrence at Week 48 was a composite endpoint defined by (1) Crohn's disease activity index (CDAI) \<150 at Week 48 \& (2) no endoscopic recurrence as defined by modified Rutgeerts score \< i2a by Week 48 \& (3) have not experienced disease recurrence. Disease recurrence was defined as (1) \>=70 point increase from baseline in CDAI score at \>8 weeks after randomization \& CDAI score \>=200 and evidence of endoscopic recurrence (Rutgeerts score \<i2a) or (2) initiation of physician-prescribed corticosteroids or increase in steroid dose of \>5 milligrams per day (mg/day) for treatment of Crohn's disease (CD) and endoscopic recurrence or (3) new draining or reopening of an internal or external fistula or (4) new perianal abscess or (5) new intra-abdominal abscess more than 3 months post index surgery. If a patient tested positive for enteric pathogen, infection should be treated and then participant should be reassessed for whether they meet disease recurrence.
Time to Disease Recurrence Baseline (Day 1) up to Week 48 Disease recurrence was defined by (1) a \>=70 point increase from baseline in CDAI score at \>8 weeks after randomization \& CDAI score \>=200 and evidence of endoscopic recurrence (Rutgeerts score \<i2a) or (2) initiation of physician-prescribed corticosteroids or increase in steroid dose of \>5 milligrams per day (mg/day) for treatment of Crohn's disease (CD) and endoscopic recurrence or (3) new draining or reopening of an internal or external fistula or (4) new perianal abscess or (5) new intra-abdominal abscess more than 3 months post index surgery. If a patient tested positive for enteric pathogen, infection should be treated and then participant should be reassessed for whether they meet disease recurrence.
Percentage of Participants With No Abdominal Pain at Week 48 At Week 48 Abdominal pain free at Week 48 is defined as abdominal pain (AP) score = 0 at Week 48. The scoring was done on a 4-point scale, ranged from 0 to 3, where 0 equals none, 1 equals mild, 2 equals moderate and 3 equals severe pain. Higher score indicated severe pain.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Baseline (Day 1) up to early termination of trial (up to Week 28) Number of participants with TEAEs and TESAEs were reported. An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE/SAE occurring at or after the initial administration of study intervention through early termination of trial (up to Week 28) was considered to be treatment emergent.
Serum Guselkumab Concentrations Over Time At Weeks 0, 8, 16 Serum guselkumab concentrations over time were reported. No summary analysis was done as study was terminated early and participant wise data were reported. This outcome measure was planned to be analyzed for "Guselkumab 200 mg + Guselkumab 100 mg" arm only.
Percentage of Participants With Steroid Free Clinical Remission at Week 48 At Week 48 Steroid free clinical remission at Week 48 is defined as CDAI \<150 and no corticosteroids within 30 days. The CDAI was a validated multi-item measure of severity of illness derived as a weighted sum of 8 different Crohn's disease-related variables. The CDAI score was assessed by collecting information on 8 different Crohn's disease-related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s), and/or opiates, and general well-being. The last 4 variables were scored over 7 days by the participant on a diary card. In general, CDAI score ranges from 0 to approximately 600Íž higher score indicated higher disease activities.
Trial Locations
- Locations (11)
Gastro Health Ohio
đşđ¸Cincinnati, Ohio, United States
Southern Star Research Institute, LLC
đşđ¸San Antonio, Texas, United States
Medical Associates Research Group, Inc.
đşđ¸San Diego, California, United States
Gastroenterology Group Of Naples
đşđ¸Naples, Florida, United States
Gastroenterolgy Associates of Central GA
đşđ¸Macon, Georgia, United States
Louisiana Research Center, LLC
đşđ¸Shreveport, Louisiana, United States
Asheville Gastroenterology Associates
đşđ¸Asheville, North Carolina, United States
Texas Digestive Disease Consultants
đşđ¸Southlake, Texas, United States
Tyler Research Institute, LLC
đşđ¸Tyler, Texas, United States
Centrum Medyczne Medyk
đľđąRzeszow, Poland
WIP Warsaw IBD Point Profesor Kierkus
đľđąWarszawa, Poland