A Study Evaluating Participants With Moderately to Severely Active Crohn's Disease

Crohn Disease Clinical Trial

— PRISM  

Official title:

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Platform Study Evaluating the Efficacy and Safety of Interventions in Participants With Moderately to Severely Active Crohn's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04102111
• Other study ID #: CR108455
• Secondary ID: 2018-000649-3867
• Status: Terminated
• Phase: Phase 2
• Start date: September 23, 2019
• Est. completion date: December 22, 2021

Study information

• Verified date: November 2022
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of JNJ-active as measured by the change in the Crohn's Disease Activity Index (CDAI) score and Simplified Endoscopic Score for Crohn's disease (SES-CD) from baseline at Week 12.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: December 22, 2021
• Est. primary completion date: November 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Have active Crohn's disease, defined as a baseline Crohn's Disease Activity Index (CDAI) score of greater than or equal to (>=) 220 and less than or equal to (<=) 450

• Have evidence of active ileocolonic Crohn's disease as assessed by an Simplified Endoscopic Score for Crohn's disease (SES-CD) score >=3 at screening by central endoscopy reading; or an elevated screening C-reactive protein (CRP) (greater than [>] 0.3 milligrams per deciliter [mg/dL] or 3.0 milligrams per liter [mg/L]) or an elevated screening fecal calprotectin (>250 micrograms per mg [mcg/mg])

• A participant with a family history of colorectal cancer, personal history of increased risk of colorectal cancer, age > 50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during screening). Adenomatous polyps must be removed before the first administration of the study intervention

• A woman of childbearing potential must have a negative highly sensitive serum (Beta-human chorionic gonadotropin [beta-hCG]) pregnancy test result at screening and a negative urine pregnancy test result at Week 0

• Has previously demonstrated inadequate response to, loss of response to, or intolerance to an approved biologic therapy (unless otherwise specified in the JNJ-67864238 intervention cohort specific criteria, that is, anti-tumor necrosis factor (TNF) alpha agents (for example, infliximab, adalimumab, certolizumab pegol], anti- interleukin (IL)-12/23 agents [for example, ustekinumab], or anti-integrin agents [for example, vedolizumab]) or has previously demonstrated an inadequate response to or failed to tolerate corticosteroids or immunomodulators (that is, 6-mercaptopurine [6-MP], azathioprine [AZA], and methotrexate [MTX]) but not a biologic, that is, the biologic nonfailures (Bio-NF) population

• Therapy for the treatment of Crohn's disease must include at least 1 of the following medications, which should have been maintained at stable doses prior to the baseline (Week 0) visit: (a) Oral 5-aminosalicylic acid (5-ASA) compounds; (b) Oral corticosteroids at a prednisone-equivalent dose <= 25 milligrams per day (mg/day), or 9 mg/day of budesonide, or 5 mg/day beclomethasone dipropionate; (c) Antibiotics being used as a primary treatment of Crohn's disease; and (d) Conventional immunomodulators (that is, AZA, 6-MP, or MTX) if participants have been taking them for at least 12 weeks and have been at a stable dose for at least 4 weeks prior to baseline

Exclusion Criteria:

• Prior exposure to an anti-IL-12/23 (that is ustekinumab) or anti-IL-23 agents or related compound (including risankizumab, brazikumab, guselkumab, mirikizumab, and related compounds). Exception is made for participants who have had minimal exposure to ustekinumab at its approved labeled dosage and have met the required wash-out criteria and have not demonstrated inadequate response or intolerance to ustekinumab

• Known allergies, hypersensitivity, or intolerance to JNJ-67864238 or its excipients

• Has complications of Crohn's disease such as symptomatic strictures or stenoses, 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 JNJ-67864238

• Has had any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before baseline

• Initiation of total (complete) or partial (supplemental) parenteral nutrition administered through any indwelling catheter less than (<) 3 weeks before baseline or anticipated to require parenteral nutrition administered through an indwelling catheter during enrollment in the study

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• JNJ-67864238
Participants will receive oral tablets of JNJ-67864238 twice daily.
• Placebo
Participants will receive oral tablets of matching placebo twice daily.

Locations

Country	Name	City	State
Argentina	Cer Instituto Medico	Buenos Aires
Argentina	CINME - Centro de Investigaciones Metabolicas	Caba
Argentina	Clínica Adventista Belgrano	Ciudad De Buenos Aires
Argentina	Sanatorio Duarte Quiroz	Cordoba
Argentina	Centro de Investigaciones Medicas Mar Del Plata	Mar Del Plata
Argentina	Fundación de Estudios Clínicos	Rosario
Germany	Universitatsklinikum Schleswig-Holstein - Kiel	Kiel
Germany	Eugastro GmbH	Leipzig
Germany	Universitatsklinikum Mannheim	Mannheim
Germany	Universitätsklinikum Ulm, Klinik für Innere Medizin II	Ulm
Italy	Policlinico di Bari Ospedale Giovanni XXIII	Bari
Italy	Policlinico Sant'Orsola Malpighi	Bologna
Italy	Azienda Ospedaliera G. Brotzu	Cagliari
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Ospedale Policlinico San Martino IRCCS	Genova
Italy	Ospedale Classificato Equiparato Sacro Cuore Don Calabria di Negrar	Negrar ( Ve)
Italy	Ospedale Maggiore della Carità	Novara
Italy	Azienda Ospedaliera di Padova	Padova
Italy	IRCCS Policlinico San Matteo, Università degli studi di Pavi	Pavia
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera G.Salvini Ospedale di Rho	RHO
Italy	Policinico A Gemelli	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Italy	A.O.Citta della Salute e della Scienza di Torino	Torino
Poland	Gastromed Kralisz Romatowski Stachurska Sp. j.	Bialystok
Poland	Endoskopia Sp z o.o.	Sopot
Poland	Centralny Szpital Kliniczny Mswia	Warsaw
Poland	WIP Warsaw IBD Point Profesor Kierkus	Warszawa
Poland	Wojskowy Instytut Medyczny	Warszawa
Russian Federation	Medical Center Meditsinskie Tekhnologii	Ekaterinburg
Russian Federation	Immanuel Kant Baltic Federal University	Kaliningrad
Russian Federation	Kemerovo Region Clinical Hospital	Kemerovo
Russian Federation	City Hospital #13 of Avtozavodsky	Nizhniy Novgorod
Russian Federation	Medical Center SibNovoMed LLC	Novosibirsk
Russian Federation	Rostov State Medical University (RSMU) based on City Hospital No. 20	Rostov-on-Don
Russian Federation	City Hospital named after St. Martyr Elizabeth	Saint-Petersburg
Russian Federation	Non State Healthcare Inst. Railway Clinical Hospital at Samara station JSC 'Russian Railways'	Samara
Russian Federation	International Medical Centre SOGAZ	St-Petersburg
Russian Federation	GBUZ Respublican Clinical Hospital n.a. GG Kuvatova	Ufa
Russian Federation	Medical diagnostic centre LTD 'MDC'	Yaroslavl
Ukraine	GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine	Kharkiv
Ukraine	MNCE'City Clinical Hospital ?2 named after prof. O.O. Shalimov' of the Kharkiv City Council	Kharkiv
Ukraine	Kyivska miska klinichna likarnia 18	Kyiv
Ukraine	Medical Center 'Ok Clinic' of International Institute of Clinical Research LLC	Kyiv
Ukraine	Danylo Halytsky Lviv National Medical University	Lviv
Ukraine	Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council	Odesa
Ukraine	Municipal Non-commercial Enterprise Ternopil University Hospital of Ternopil Regional Council	Ternopil
Ukraine	MNCE Zakarpatska Regional Clinical Hospital named after A Novak of Zakarpatska Regional Council	Uzhgorod
Ukraine	Medical Center Ltd 'Health Clinic'	Vinnytsya
Ukraine	VNMUn.af.Pyrogova,CNE Vinnytsia Regional Clinical Hospital n.af.Pyrogova Vinnytsia Regional Council	Vinnytsya
United States	Northshore Gastroenterology Research, LLC	Beachwood	Ohio
United States	Gastro Florida	Clearwater	Florida
United States	Peak Gastroenterology Associates	Colorado Springs	Colorado
United States	CroNOLA, LLC	Houma	Louisiana
United States	NYU Langone Long Island Clinical Research Associates	Lake Success	New York
United States	Gastroenterology Associates of Central GA	Macon	Georgia
United States	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Digestive Disease Specialists Inc	Oklahoma City	Oklahoma
United States	Washington University	Saint Louis	Missouri
United States	Gastroenterology Research of San Antonio	San Antonio	Texas
United States	Northshore Gastroenterology Research, LLC	Westlake	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Germany,  Italy,  Poland,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12	CDAI is a validated measure of illness severity derived as sum of 8 different Crohn's disease (CD)-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s)/opiates, and general well-being). Last 3 variables were scored over 7 days by participant on diary card. Score ranges from 0 to 600; higher score=higher disease activities. Participants who had incomplete data (less than or equal to [<=]4 component values missing) at the visit, had their last available component value carried forward to calculate CDAI Score. Participants who had prohibited change in concomitant CD medication, CD-related surgery or discontinued intervention due to lack of efficacy or adverse event of worsening CD prior to Week 12 had their baseline value carried forward. Participants who had discontinuation of intervention due to corona virus disease-19 related reasons had their CDAI data as missing.	Baseline and Week 12
Secondary	Change From Baseline in Simplified Endoscopic Score for Crohn's Disease (SES-CD) at Week 12	SES-CD scoring system assesses disease severity in participants with CD. It is based on evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any lesions and presence/type of narrowing [strictures/ stenosis clinically] across 5 predefined ileocolonic segments (ileum, right colon, transverse colon, left colon and rectum). Each component score= 0 to 3 for each segment, total score calculated as sum of all component scores for all segments. Maximum sub-score for narrowings=11 points. Total SES-CD score ranges=0 to 56, where higher scores=more severe disease. Participants who had prohibited change in concomitant CD medication, CD-related surgery or discontinued intervention due to lack of efficacy/AE of worsening CD prior to Week 12 had their baseline value carried forward. Participants who had discontinuation of intervention due to COVID-19 related reasons had their CDAI data as missing.	Baseline and Week 12
Secondary	Percentage of Participants With Clinical Response at Week 12	Percentage of participants with clinical response at Week 12 were reported. Clinical response is defined as a greater than or equal to (>=) 100-point reduction from baseline in CDAI score or CDAI score less than (<) 150. The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 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 3 variables were scored over 7 days by the participant on a diary card. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities.	Week 12
Secondary	Percentage of Participants With Clinical Remission at Week 12	Percentage of participants with clinical remission at Week 12 were reported. Clinical remission is defined as CDAI score <150. The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 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 3 variables were scored over 7 days by the participant on a diary card. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities.	Week 12
Secondary	Percentage of Participants With Patient-reported Outcome (PRO)-2 Remission at Week 12	Percentage of participants with PRO-2 remission at Week 12 were reported. PRO-2 remission is defined as abdominal pain (AP) mean daily score (AP component of the CDAI) <=1 and stool frequency (SF) mean daily score of <=3, that is, AP <=1 and SF <=3. PRO-2 is a composite index consisting of weighted scoring of both variables. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease.	Week 12
Secondary	Percentage of Participants With Endoscopic Response at Week 12	Endoscopic response is defined as at least 50 percent (%) improvement from baseline in SES-CD score. SES-CD scoring system assesses disease severity in participants with CD. It is based on evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any lesions and presence/type of narrowing [strictures/ stenosis clinically] across 5 predefined ileocolonic segments (ileum, right colon, transverse colon, left colon and rectum). Each component score=0 to 3 for each segment, total score calculated as sum of all component scores for all segments. Maximum sub-score for narrowings=11 points. Total SES-CD score range=0 to 56, where higher score=more severe disease.	Week 12
Secondary	Percentage of Participants With Endoscopic Remission at Week 12	Endoscopic remission defined as an SES-CD score of <=2. SES-CD scoring system assesses disease severity in participants with CD. It is based on evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any lesions and presence/type of narrowing [strictures/ stenosis clinically] across 5 predefined ileocolonic segments (ileum, right colon, transverse colon, left colon and rectum). Each component score=0 to 3 for each segment, total score calculated as sum of all component scores for all segments. Maximum sub-score for narrowings=11 points. Total SES-CD score range=0 to 56, where higher score=more severe disease.	Week 12