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

Inflammatory Bowel Diseases Clinical Trial

— ADAPT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02566889
• Other study ID #: CR108044
• Secondary ID: C0168IBD40202015
• Status: Terminated
• Phase: Phase 4
• Start date: April 2016
• Est. completion date: July 2019

Study information

• Verified date: July 2020
• Source: Janssen Scientific Affairs, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 53
• Est. completion date: July 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 16 Years

Eligibility

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)

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Scientific Affairs, LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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