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

A Phase 4, Multicenter, Open-label Study of Serum Infliximab Concentrations and Efficacy and Safety of Dose Escalation in Pediatric Patients With Inflammatory Bowel Disease

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.

Study Overview

• Status: Terminated
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Drug: Infliximab

Detailed Description

This is a multicenter (when more than one hospital or medical school team work on a medical research study), prospective (study following participants forward in time), open-label (all people know the identity of the intervention) study of infliximab in pediatric participants with inflammatory bowel disease. The study consists of 3 Phases: screening Phase (up to 4 weeks), open-label treatment Phase (56 weeks) and follow up safety Phase (8 weeks). The duration of participation in the study for each participant is approximately up to 68 weeks (including screening period). Participants' efficacy and safety outcomes will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
  • Ontario
    • Hamilton, Ontario, Canada
    • London, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
    • Sherbrooke, Quebec, Canada
• United States
  • Arizona
    • Phoenix, Arizona, United States
  • California
    • Los Angeles, California, United States
    • San Francisco, California, United States
  • Connecticut
    • Hartford, Connecticut, United States
  • Delaware
    • Wilmington, Delaware, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
    • Peoria, Illinois, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Louisiana
    • Shreveport, Louisiana, United States
  • Maine
    • Portland, Maine, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
    • Waltham, Massachusetts, United States
  • Minnesota
    • Rochester, Minnesota, United States
    • Saint Paul, Minnesota, United States
  • Missouri
    • Kansas City, Missouri, United States
  • New York
    • Mineola, New York, United States
    • New York, New York, United States
    • Stony Brook, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
  • Ohio
    • Cleveland, Ohio, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
  • South Carolina
    • Charleston, South Carolina, United States
  • Texas
    • Dallas, Texas, United States
    • Fort Worth, Texas, United States
  • Virginia
    • Fairfax, Virginia, United States
  • Wisconsin
    • Madison, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Group; 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; 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.; Other Names: Remicade
Experimental: Reference Group; 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; 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.; Other Names: Remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Clinical Response Through 56 Weeks After Dose Escalation	Sustained clinical response at Week 56 was defined as achieving clinical response per the primary OM definitions at Week 16 and maintaining clinical response at 1 year after dose escalation (Week 56). Clinical response was defined as a decrease from baseline in PCDAI of >= 15 points with total score of =< 30 points (for CD participants) and a decrease from baseline in partial Mayo score of >=2 points and >=30% and a decrease in rectal bleeding sub-score by >= 1 point or achievement of an absolute sub-score of =< point (for UC participants). Data for this OM was planned to be analyzed for the DE group only.	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	Abdominal and loose/watery stool frequency was evaluated by using the relevant sub-scores of the PCDAI. 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 the DE group only.	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	Change from baseline in abdominal pain using the Wong-Baker FACES scale at Week 16 and Week 56 in CD participants was reported. The Wong-Baker FACES Pain Scale is a pain scale that combines pictures and numbers to allow pain to be rated by children over the age of 3. The scale shows a series of faces ranging from a happy face at 0, "No hurt" to a crying face at 10 "Hurts worst". The participant must choose the face that best describes how they are feeling. Data for this OM was planned to be analyzed for the DE group only.	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	Change from baseline in Absolute stool frequency at Week 16 and Week 56 in CD participants were reported. 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. An absolute stool frequency subscore of =<1 point was indicative of mild disease. Data for this OM was planned to be analyzed for the DE group only.	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	Change from baseline in Stool frequency sub-score of the partial Mayo score at Week 16 and Week 56 in UC participants were reported. 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 PGA) with each ranging from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). An absolute stool frequency subscore of <=1 point was indicative of mild disease. Higher scores indicate more severe disease. Data for this OM was planned to be analyzed for the DE group only.	Baseline, Week 16 and Week 56
Change From Baseline in Rectal Bleeding Sub-Scores of the Partial Mayo Score at Week 16 and Week 56 in UC Participants	Change from baseline in rectal bleeding sub-scores of the partial Mayo score at Week 16 and Week 56 in UC participants were reported. 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 PGA) with each ranging from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). An absolute rectal bleeding subscore of <=1 point was indicative of mild disease. Higher scores indicate more severe disease. Data for this OM was planned to be analyzed for the DE group only.	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 UC Participants	Change from baseline in Abdominal pain using the Wong-Baker FACES scale at Week 16 and Week 56 in UC participants were reported. The Wong-Baker FACES Pain Scale is a pain scale that combines pictures and numbers to allow pain to be rated by children over the age of 3. The scale shows a series of faces ranging from a happy face at 0, "No hurt" to a crying face at 10 "Hurts worst". The participant must choose the face that best describes how they are feeling. Data for this OM was planned to be analyzed for the DE group only.	Baseline, Week 16 And Week 56
Change From Baseline in Absolute Stool Frequency at Week 16 and Week 56 in UC Participants	Change from baseline in absolute stool frequency at Week 16 and Week 56 in UC participants were reported. Data for this OM was planned to be analyzed for the DE group only.	Baseline, Week 16 And Week 56
Correlation of Wong-Baker FACES Scale With Clinical Remission and Response at Week 16	The Wong-Baker FACES Pain Scale is a pain scale that combines pictures and numbers to allow pain to be rated by children over the age of 3. The scale shows a series of faces ranging from a happy face at 0, "No hurt" to a crying face at 10 "Hurts worst". Data for this OM was planned to be analyzed for the DE group only. Statistical test of the hypothesis (regression model) was not performed due to insufficient data being collected to permit analysis.	Week 16
Relationship Between Abdominal Pain PCDAI Sub-Score And the Wong-Baker Faces Scale For CD Participants	PCDAI is validated clinical tool used to assess disease severity in pediatric CD participants. PCDAI collects information on disease-related variables:Total number of liquid stools, abdominal pain, and general well-being (scored by participants or participant's legal representative);Extra-intestinal manifestations;Physical examinations of abdominal mass, perirectal disease;Weight change, height change or, height velocity;Hematocrit;erythrocyte sedimentation rate; albumin. PCDAI score is calculated as sum of individual component scores and ranges from 0-100 points. Wong-Baker FACES Pain Scale combines pictures and numbers to allow pain to be rated by children over age of 3. Scale shows a series of faces ranging from a happy face at 0, "No hurt" to crying face at 10 "Hurts worst". Data for this OM was planned to be analyzed for the DE group only. Statistical test of the hypothesis (regression model) was not performed due to insufficient data being collected to permit analysis.	Week 16 and 56

Collaborators and Investigators

• Sponsor: Janssen Scientific Affairs, LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: October 1, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): August 6, 2020
• Last Update Submitted That Met QC Criteria: July 28, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Infliximab; Pediatric Participants; Dose Escalation; Pediatric Ulcerative Colitis; Pediatric Crohn's Disease; Pediatric Inflammatory Bowel Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: CR108044; C0168IBD4020 (Other Identifier: Janssen Scientific Affairs, LLC); 2015-001653-32 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No