CAMEO: Clinical, Imaging, and Endoscopic Outcomes of Children Newly Diagnosed With Crohn's Disease

Sponsor

Connecticut Children's Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05781152

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Emory University (Other), Children's Hospital Medical Center, Cincinnati (Other), University of North Carolina, Chapel Hill (Other)

900

Enrollment

Locations

Anticipated Duration (Months)

33.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Crohn's disease (CD) is a condition that causes inflammation (swelling, redness) of the lining and wall of the small intestine, large intestine, or both. CD may be associated with abdominal cramps/pain, diarrhea, blood in the stool, weight loss, or delayed growth in children. While the exact cause of CD is not certain it is thought that the immune system located in the intestine reacts abnormally to the large number of bacteria contained there. The investigators think that diet, exposure to antibiotics early in life, and having a family history of CD puts people at increased risk for developing CD. In order to decrease the inflammation doctors use what is called biologic therapy with anti-TNF molecules that can be given through an intravenous or shots. TNF is a chemical made by white blood cells that is involved in inflammation. When this type of treatment is given early after diagnosis it is more effective than when it is given later. The investigators have learned that it is important to give the optimum (ideal) amount of this medicine guided by certain blood tests. The investigators also know that not everyone responds to this therapy but do not understand the reasons for this variability between people. The CAMEO study has been started to help understand what factors are important in determining whether a child with CD completely heals the inflammation after anti-TNF therapy. The investigators will do that by measuring certain markers of inflammation in the blood and stool and by looking at a person's genes (DNA) and how inflammation is controlled in the intestine. These inflammation tests will be done before, during, and after one year of anti-TNF therapy. The investigators will determine how much healing has taken place by comparing the results of the colonoscopy and a special type of MRI that are both done before anti-TNF and then again one year later. The goal in treating CD is to heal both the lining and the wall of the intestine. Children ages 6-17 years who are thought to have CD and are about to undergo their diagnostic colonoscopy are eligible to be enrolled. If they are found to indeed have CD and start an anti-TNF medicine within 6 months they can continue in the study. There are no increased risks of participating in this study beyond those normally associated with having CD and its treatment. By better understanding why the bowel does or does not heal, doctors will be better able to provide personalized care.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Biological: infliximab, adalimumab

Detailed Description

Study Sites: Approximately 27 pediatric clinical centers in North America Study Period:

Planned enrollment period - 3 years Planned duration of the study: 5 years Primary Study Objective: Identify clinical, radiologic, genomic, immune, microbial and transcriptomic factors associated with complete intestinal healing (CH) in the context of optimized anti-TNF therapy in children with newly diagnosed CD Secondary Study Objective: Identify clinical, radiologic, genomic, immune, microbial and transcriptomic factors associated with endoscopic healing only, transmural healing by MRE only, endoscopic response only, transmural response only, clinical remission, fecal calprotectin normalization, in the context of optimized anti-TNF therapy in children with newly diagnosed CD Study Design: Prospective multicenter open label single arm clinical trial with 2-phase enrollment Sample Size: Phase 1: 900; Phase 2: 550

Study Design

Study Type:

Observational

Anticipated Enrollment :

900 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Clinical, Imaging, and Endoscopic Outcomes of Children Newly Diagnosed With Crohn's Disease

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2028

Anticipated Study Completion Date :

Apr 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Anti-tumor necrosis factor (TNF) Patients newly diagnosed with pediatric-onset Crohn's disease starting anti-TNF therapy within 6 months of diagnosis	Biological: infliximab, adalimumab Anti-TNF therapy guided by therapeutic drug monitoring Other Names: Remicade, Inflectra, Renflexis, Avsola, Humira, Amgevita, Hulio, Hadlima, Hyrimoz, Idacio

Arm

Intervention/Treatment

Anti-tumor necrosis factor (TNF)

Patients newly diagnosed with pediatric-onset Crohn's disease starting anti-TNF therapy within 6 months of diagnosis

Biological: infliximab, adalimumab

Anti-TNF therapy guided by therapeutic drug monitoring

Other Names:

Remicade, Inflectra, Renflexis, Avsola, Humira, Amgevita, Hulio, Hadlima, Hyrimoz, Idacio

Outcome Measures

Primary Outcome Measures

Complete healing (CH) [52 weeks from anti-TNF start]
The achievement of complete healing (CH) 52 weeks after initiation of anti-TNF therapy guided by ROADMAB™ (therapeutic drug monitoring) as evidenced by a composite of all of the following four features below: Endoscopic healing (EH) determined by centrally read ileocolonoscopy (total SES-CD score <3) Transmural healing (TH) determined by centrally read MRE (no segmental MaRIAs score of ≥1) Corticosteroid free for a minimum of 4 weeks The absence of either intestinal resection or the addition of a nutritional, biological or small molecule therapeutic agent other than anti-TNF± concomitant IM

Secondary Outcome Measures

Endoscopic mucosal healing only [52 weeks]
Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Endoscopic mucosal healing only (total Simple Endoscopic Score - Crohn's Disease (SES-CD) <3)
Transmural healing only [52 weeks]
Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Transmural healing only (no segmental simplified magnetic resonance index of activity (MaRIAs) score ≥1)
Clinical remission [52 weeks]
Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Clinical remission (weighted Pediatric Crohn's Disease Activity Index (wPCDAI) < 12.5)
Fecal calprotectin [52 weeks]
Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Fecal calprotectin <250 ug/g
Endoscopic response [52 weeks]
Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Endoscopic response: 50% reduction in SES-CD
Transmural response [52 weeks]
Following approximately 52 weeks of anti-TNF therapy guided by the ROADMAB™ Clinical Decision Support Tool (CDST), with a minimum of 4 weeks of being corticosteroid free, and in the absence of either intestinal resection or the addition of a biological or small molecule therapeutic agent other than anti-TNF± concomitant IM: Transmural response: 50% reduction in MaRIAs

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Phase 1 Inclusion Criteria (all must be fulfilled)

Age ≥ 6 years and < 18 years at enrollment
Suspected diagnosis of CD
Stool culture if performed that is negative for routine enteric pathogens (Salmonella, Shigella, Campylobacter, E. coli 0157:H7) and Clostridium difficile toxin in patients presenting with diarrhea. If history of C. difficile then a minimum of 6 weeks duration from treatment start and negative repeat stool for C. difficile toxin.
Parent/guardian consent and patient assent
Ability to remain in follow-up for up to 6 months of initial observation followed by a minimum of 52 weeks after possible start of anti-TNF therapy

Phase 1 Exclusion Criteria

Diagnosis of CD following abdominal resectional surgery/appendectomy at initial presentation
Investigator judgment that patient has high likelihood (>50%) of needing bowel resection within 3 months of diagnosis (i.e., presentation with perforation, bowel obstruction from stricture)
Use of any oral corticosteroid (CS) for non-gastrointestinal indication within the four weeks prior to diagnostic assessment and biosampling (e.g., asthma)
Use of any investigational drug within the past four weeks prior to diagnostic assessment and sampling
Pregnancy
Patients with poorly controlled medical conditions (e.g. diabetes, congestive heart failure)
Previous treatment with immunomodulators or anti-TNF therapy for other medical conditions (e.g., juvenile idiopathic arthritis) at any time prior to enrollment
Previous treatment with non-anti TNF biologics or small molecules for non-IBD indications in the past 6 months

Phase 2 Inclusion Criteria (all must be fulfilled)

Met all eligibility criteria for Phase 1 and participated in Phase 1
Diagnosed with active luminal CD involving the terminal ileum and/or colon by endoscopic and/or radiographic evidence
Magnetic Resonance Enterography (MRE) imaging within 6 weeks of ileocolonoscopy and no more than 4 weeks after starting initial therapy. A limited 'research protocol' MRE is acceptable in participants who have undergone a clinical CTE during their initial diagnostic evaluation; see Manual of Procedures for details.
Received at least one of the following as initial therapy upon diagnosis:
Corticosteroids
Immunomodulator
Defined nutritional therapy
Anti-TNF (adalimumab or infliximab)
Commenced adalimumab or infliximab anti-TNF therapy guided by ROADMAB™ CDST as first therapy or within 180 days of first therapy, with or without concomitant immunomodulator
Had ileal and rectal biopsies
Parent/guardian re-consent and patient re-assent
Ability to remain in follow-up for a minimum of 52 weeks after start of anti-TNF therapy

Phase 2 Exclusion Criteria

Diagnosis of CD using video capsule endoscopy only with normal ileocolonoscopy and normal MRE
Orofacial CD only
Esophageal, gastric, duodenal, and/or jejunal CD only
Severe complex fistulizing perianal disease +/- abscess, or perianal disease requiring surgical intervention or likely to require on-going surgical intervention possibly including diversion
Perianal CD only with no evidence of luminal disease
Internal fistulizing disease at diagnosis
Initial inflammatory bowel disease (IBD) treatment with non-anti-TNF biologic or small molecule therapy
Received any anti-TNF agent other than adalimumab or infliximab
Investigator judgment that patient unlikely to return for clinical, endoscopic or MRE follow-up
Inability to have MRE because of claustrophobia or other reasons
Incomplete lower endoscopic diagnostic evaluation where the investigation is terminated prior to intubation of the ileum
Video of baseline endoscopy not available for central reading
Underwent bowel resection within 3 months of initial therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Cedars-Sinai	Los Angeles	California	United States	90048
3	Rady Children's Hospital - San Diego and University of California, San Diego	San Diego	California	United States	92123
4	UCSF Benioff Children's Hospitals	San Francisco	California	United States	94158
5	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
6	Emory University	Atlanta	Georgia	United States	30328
7	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana	United States	46202
8	The Johns Hopkins Children's Medical Center	Baltimore	Maryland	United States	21287
9	Boston Children's Hospital	Boston	Massachusetts	United States	02115
10	University of Michigan	Ann Arbor	Michigan	United States	48109
11	Goryeb Children's Hospital/Morristown Medical Center/Atlantic Children's Health	Morristown	New Jersey	United States	07960
12	Cohen Children's Medical Center of NY	Lake Success	New York	United States	11042
13	Columbia University Medical Center	New York	New York	United States	10032
14	Levine Children's	Charlotte	North Carolina	United States	28203
15	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
16	UH/Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
17	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
18	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19146
19	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
20	Rhode Island Hospital	Providence	Rhode Island	United States	02903
21	Baylor College of Medicine / Texas Children's Hospital	Houston	Texas	United States	77030
22	Seattle Children's Hospital	Seattle	Washington	United States	98105
23	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
24	Stollery Children's Hospital	Edmonton	Alberta	Canada	T6G 1C9
25	Children's Hospital Western Ontario	London	Ontario	Canada	N6A 5W9
26	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
27	Toronto SickKids Hospital	Toronto	Ontario	Canada	M5G1X8

Sponsors and Collaborators

Connecticut Children's Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Emory University
Children's Hospital Medical Center, Cincinnati
University of North Carolina, Chapel Hill

Investigators

Principal Investigator: Jeffrey S Hyams, MD, Connecticut Children's Medical Center
Principal Investigator: Subra Kugathasan, MD, Emory University
Principal Investigator: Lee Denson, MD, Children's Hospital Medical Center, Cincinnati