An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease

NCT02566889 | Terminated Phase 4 Results DMC

• 3 other identifiers: CR108044C0168IBD40202015-001653-32
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 36

Brief Summary

The purpose of this study is to evaluate whether trough serum infliximab concentrations at the time of loss of clinical response will identify pediatric participants with inflammatory bowel disease (IBD) who would benefit (regain clinical response) from dose escalation above the currently approved dose \[5 milligram (mg)/kilogram (kg) every 8 weeks (q8wk)\] and the safety of that dose escalation.

Conditions

Inflammatory Bowel Diseases

Keywords

Pediatric Inflammatory Bowel Disease; Infliximab; Pediatric Participants; Pediatric Ulcerative Colitis; Pediatric Crohn's Disease; Dose Escalation

Outcome Measures

Primary Outcomes (2)

• Clinical Response at Week 16 After Dose Escalation as Evaluated by Pediatric Crohn's Disease Activity Index (PCDAI) in Crohn's Disease (CD) Participants

  Clinical response was defined as Crohn's disease (CD) participants with decrease from baseline in PCDAI of greater than or equal to (\>=) 15 points with total score of less than or equal to (\<=) 30 points. PCDAI includes three history items (abdominal pain, number of liquid stools, general wellbeing), five physical examination items (abdominal examination, perirectal disease, extraintestinal manifestations, weight, height), and three laboratory tests (hematocrit, albumin, erythrocyte sedimentation rate). Items are scored on a three-point scale (zero, 5, or 10 points) except for hematocrit and erythrocyte sedimentation rate which are scored as zero, 2.5 or 5 points. PCDAI scores can range from zero to 125 with higher scores indicating more active disease. Data for this OM was planned to be analyzed for Dose escalation (DE) group only.

  Week 16

• Clinical Response at Week 16 After Dose Escalation as Evaluated by Mayo Score in Ulcerative Colitis (UC) Participants

  Clinical Response as per Mayo score was defined as decrease from baseline in partial Mayo score of \>= 2 points and \>= 30 percent (%) and decrease in rectal bleeding sub-score by \>= 1 point or achievement of an absolute sub-score of less than or equal to (\<=) 1 point (for UC participants). A Partial Mayo Score which is Mayo score without endoscopy ranges from 0 (normal or inactive disease) to 9 (severe disease) and calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment \[PGA\]) with each ranging from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). Data for this OM was planned to be analyzed for the DE group only.

  Week 16

Secondary Outcomes (10)

• Sustained Clinical Response Through 56 Weeks After Dose Escalation

  Up to Week 56

• Change From Baseline in Abdominal Pain and Loose/Watery Stool Frequency Sub-scores of the PCDAI at Week 16 and Week 56 in CD Participants

  Baseline, Week 16 and Week 56

• Change From Baseline in Abdominal Pain Using the Wong-Baker FACES Scale at Week 16 and Week 56 in CD Participants

  Baseline, Week 16 and Week 56

• Change From Baseline in Absolute Stool Frequency Based on PCDAI Score at Week 16 and Week 56 in CD Participants

  Baseline, Week 16 and Week 56

• Change From Baseline in Stool Frequency Sub-Score of the Partial Mayo Score at Week 16 and Week 56 in UC Participants

  Baseline, Week 16 and Week 56

Study Arms (2)

Dose Escalation Group

EXPERIMENTAL

Participants must have completed: a) recommended infliximab induction dosing regimen of 5 milligram (mg)/kilogram (kg) at Weeks 0, 2, and 6, followed by at least 1 maintenance doses of 5 mg/kg every 8 weeks (q8wk); or b) induction regimen with doses \>6 mg/kg and have received at least 2 maintenance doses of 5 mg/kg q8wk with clinical response for at least 28 days after the most recent 5 mg/kg maintenance dose; or c) maintenance doses \>6 mg/kg within past 6 months and at least 2 maintenance doses of 5 mg/kg q8wk with clinical response for at least 28 days after the most recent 5 mg/kg maintenance dose; d) must have lost clinical response, after first or subsequent q8wk maintenance dose of infliximab 5 mg/kg for participants who have completed the recommended infliximab induction dosing regimen or, after most recent (second or later) q8wk maintenance dose of infliximab 5 mg/kg for participants with an induction regimen with doses \>6 mg/kg or with previous maintenance doses \>6 mg/kg.

Drug: Infliximab

Reference Group

EXPERIMENTAL

Participants must have completed: a) the recommended infliximab induction dosing regimen of 5 mg/kg at Weeks 0, 2, and 6, and have maintained a stable clinical response to infliximab after at least 1 maintenance doses of 5 mg/kg q8wk; or b) an induction regimen with doses \>6 mg/kg and have received at least 2 maintenance doses of 5 mg/kg q8wk and have maintained clinical response for at least 28 days after the most recent 5 mg/kg maintenance dose 5 mg/kg maintenance dose; or c) maintenance doses \>6 mg/kg within the past 6 months and at least 2 maintenance doses of 5 mg/kg q8wk and have maintained a clinical response for at least 28 days after the most recent 5 mg/kg maintenance dose 5 mg/kg maintenance dose.

Drug: Infliximab

Interventions

Infliximab DRUG

Participants in the dose escalation group will escalate dose from infliximab 5 mg/kg q8w to 10 mg/kg q8w at the time of loss response. Participants in the reference group will be maintained on infliximab 5 mg/kg q8w.

Also known as: Remicade

Dose Escalation Group; Reference Group

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Must have a biopsy-confirmed diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) prior to study entry
• Must meet concomitant medication stability criteria as specified in protocol
• Is considered eligible according to the tuberculosis (TB) Screening criteria specified in protocol
• Must have negative stool results for enteric pathogens. Stool studies must include a stool culture and Clostridium difficile toxin assay. These must have been performed during Screening or the current episode of disease exacerbation as long as the stool studies were performed within 4 months prior to the first administration of infliximab at Week 0
• Must have screening laboratory test results as specfied in the protocol
• Must be up to date with all immunizations in agreement with current local immunization guidelines for immunosuppressed participants prior to Screening
• Must not have discontinued infliximab therapy

You may not qualify if:

• Must not require, or must not have required, within the 2 months prior to Screening, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intraabdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from infliximab treatment
• Must not have presence or history of colonic or small bowel obstruction within 6 months prior to Screening, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (example, dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy)
• Must not have local manifestations of CD, such as fistulae, strictures, abscesses, or other disease complications for which surgery might be indicated. Enterocutaneuous fistulae for which surgery is not indicated, are allowed
• Must not have presence of a stoma
• Must not have documented short bowel syndrome (more than 100 centimeter in total of small bowel resected)

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead

Study Sites (36)

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Phoenix, Arizona, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Hartford, Connecticut, United States

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Wilmington, Delaware, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Peoria, Illinois, United States

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Indianapolis, Indiana, United States

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Shreveport, Louisiana, United States

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Portland, Maine, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Waltham, Massachusetts, United States

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Rochester, Minnesota, United States

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Saint Paul, Minnesota, United States

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Kansas City, Missouri, United States

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Mineola, New York, United States

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New York, New York, United States

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Stony Brook, New York, United States

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Chapel Hill, North Carolina, United States

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Cleveland, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Fairfax, Virginia, United States

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Madison, Wisconsin, United States

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Vancouver, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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Hamilton, Ontario, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Sherbrooke, Quebec, Canada

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MeSH Terms

Conditions

Inflammatory Bowel Diseases; Pediatric ulcerative colitis; Pediatric Crohn's disease

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study was terminated due to the inability to enroll a sufficient number of the required participants.

Results Point of Contact

• Title: Director
• Organization: Janssen Scientific Affairs

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2015
• First Posted: October 2, 2015
• Study Start: April 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: February 4, 2025
• Results First Posted: June 9, 2020

Record last verified: 2025-01

Locations

US (29); CA (7)