ADAPT: An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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 Design
Arms and Interventions
| 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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- Clinical Response at Week 16 After Dose Escalation as Evaluated by Pediatric Crohn's Disease Activity Index (PCDAI) in Crohn's Disease (CD) Participants [Week 16]
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.
- Clinical Response at Week 16 After Dose Escalation as Evaluated by Mayo Score in Ulcerative Colitis (UC) Participants [Week 16]
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.
Secondary Outcome Measures
- Sustained Clinical Response Through 56 Weeks After Dose Escalation [Up to Week 56]
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.
- 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]
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.
- 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 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.
- 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 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.
- 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]
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.
- Change From Baseline in Rectal Bleeding Sub-Scores of the Partial Mayo Score at Week 16 and Week 56 in UC Participants [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 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.
- Change From Baseline in Abdominal Pain Using the Wong-Baker FACES Scale at Week 16 and Week 56 in UC 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 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.
- Change From Baseline in Absolute Stool Frequency at Week 16 and Week 56 in UC Participants [Baseline, Week 16 And Week 56]
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.
- Correlation of Wong-Baker FACES Scale With Clinical Remission and Response at Week 16 [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.
- Relationship Between Abdominal Pain PCDAI Sub-Score And the Wong-Baker Faces Scale For CD Participants [Week 16 and 56]
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.
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix | Arizona | United States | ||
| 2 | Los Angeles | California | United States | ||
| 3 | San Francisco | California | United States | ||
| 4 | Hartford | Connecticut | United States | ||
| 5 | Wilmington | Delaware | United States | ||
| 6 | Atlanta | Georgia | United States | ||
| 7 | Chicago | Illinois | United States | ||
| 8 | Peoria | Illinois | United States | ||
| 9 | Indianapolis | Indiana | United States | ||
| 10 | Shreveport | Louisiana | United States | ||
| 11 | Portland | Maine | United States | ||
| 12 | Baltimore | Maryland | United States | ||
| 13 | Boston | Massachusetts | United States | ||
| 14 | Waltham | Massachusetts | United States | ||
| 15 | Rochester | Minnesota | United States | ||
| 16 | Saint Paul | Minnesota | United States | ||
| 17 | Kansas City | Missouri | United States | ||
| 18 | Mineola | New York | United States | ||
| 19 | New York | New York | United States | ||
| 20 | Stony Brook | New York | United States | ||
| 21 | Chapel Hill | North Carolina | United States | ||
| 22 | Cleveland | Ohio | United States | ||
| 23 | Philadelphia | Pennsylvania | United States | ||
| 24 | Pittsburgh | Pennsylvania | United States | ||
| 25 | Charleston | South Carolina | United States | ||
| 26 | Dallas | Texas | United States | ||
| 27 | Fort Worth | Texas | United States | ||
| 28 | Fairfax | Virginia | United States | ||
| 29 | Madison | Wisconsin | United States | ||
| 30 | Vancouver | British Columbia | Canada | ||
| 31 | Halifax | Nova Scotia | Canada | ||
| 32 | Hamilton | Ontario | Canada | ||
| 33 | London | Ontario | Canada | ||
| 34 | Toronto | Ontario | Canada | ||
| 35 | Montreal | Quebec | Canada | ||
| 36 | Sherbrooke | Quebec | Canada |
Sponsors and Collaborators
- Janssen Scientific Affairs, LLC
Investigators
- Study Director: Janssen Scientific Affairs, LLC Clinical Trial, Janssen Scientific Affairs, LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- CR108044
- C0168IBD4020
- 2015-001653-32
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Reference arm was planned only for safety analysis in participants being treated with labeled dosing of infliximab. |
| Arm/Group Title | Reference Group | Dose Escalation Group |
|---|---|---|
| Arm/Group Description | Participants received infliximab 5 mg/kg intravenous (IV) infusion every 8 weeks (q8wk) up to 56 weeks with a final safety visit at Week 64. Those who lost clinical response during participation in the study were eligible to cross over to the Dose Escalation Group and receive a total of 56 weeks of therapy with infliximab, which included duration of therapy while in the Reference Group prior to dose escalation. | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Period Title: Overall Study | ||
| STARTED | 45 | 8 |
| Cross-over to Dose Escalation Group | 1 | 0 |
| COMPLETED | 32 | 3 |
| NOT COMPLETED | 13 | 5 |
Baseline Characteristics
| Arm/Group Title | Reference Group | Dose Escalation Group | Total |
|---|---|---|---|
| Arm/Group Description | Participants received infliximab 5 mg/kg intravenous (IV) infusion every 8 weeks (q8wk) up to 56 weeks with a final safety visit at Week 64. Those who lost clinical response during participation in the study were eligible to cross over to the Dose Escalation Group and receive a total of 56 weeks of therapy with infliximab, which included duration of therapy while in the Reference Group prior to dose escalation. | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. | Total of all reporting groups |
| Overall Participants | 45 | 8 | 53 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
14.1
(1.9)
|
12.9
(2.7)
|
13.9
(2.05)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
16
35.6%
|
4
50%
|
20
37.7%
|
| Male |
29
64.4%
|
4
50%
|
33
62.3%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
4.4%
|
0
0%
|
2
3.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
4.4%
|
0
0%
|
2
3.8%
|
| White |
37
82.2%
|
7
87.5%
|
44
83%
|
| More than one race |
3
6.7%
|
1
12.5%
|
4
7.5%
|
| Unknown or Not Reported |
1
2.2%
|
0
0%
|
1
1.9%
|
| Region of Enrollment (Count of Participants) | |||
| Canada |
3
6.7%
|
1
12.5%
|
4
7.5%
|
| United States |
42
93.3%
|
7
87.5%
|
49
92.5%
|
Outcome Measures
| Title | Clinical Response at Week 16 After Dose Escalation as Evaluated by Pediatric Crohn's Disease Activity Index (PCDAI) in Crohn's Disease (CD) Participants |
|---|---|
| Description | 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. |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 5 |
| Number [Participants] |
4
8.9%
|
| Title | Clinical Response at Week 16 After Dose Escalation as Evaluated by Mayo Score in Ulcerative Colitis (UC) Participants |
|---|---|
| Description | 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. |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 1 |
| Number [Participants] |
0
0%
|
| Title | Sustained Clinical Response Through 56 Weeks After Dose Escalation |
|---|---|
| Description | 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. |
| Time Frame | Up to Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 4 |
| Number [Participants] |
2
4.4%
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 16 and Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As the study was terminated early with lesser participants and lesser sample size, data for this OM was not collected. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 0 |
| Title | Change From Baseline in Abdominal Pain Using the Wong-Baker FACES Scale at Week 16 and Week 56 in CD Participants |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 16 and Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 5 |
| Participant 1: Change at Week 16 |
0
|
| Participant 1: Change at Week 56 |
0
|
| Participant 2: Change at Week 16 |
0
|
| Participant 2: Change at Week 56 |
NA
|
| Participant 3: Change at Week 16 |
0
|
| Participant 3: Change at Week 56 |
NA
|
| Participant 4: Change at Week 16 |
1
|
| Participant 4: Change at Week 56 |
-4
|
| Participant 5: Change at Week 16 |
-5
|
| Participant 5: Change at Week 56 |
-5
|
| Title | Change From Baseline in Absolute Stool Frequency Based on PCDAI Score at Week 16 and Week 56 in CD Participants |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 16 and Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 5 |
| Participant 1: Change at Week 16 |
-9
|
| Participant 1: Change at Week 56 |
-3
|
| Participant 2: Change at Week 16 |
2
|
| Participant 2: Change at Week 56 |
NA
|
| Participant 3: Change at Week 16 |
-1
|
| Participant 3:Change at Week 56 |
NA
|
| Participant 4: Change at Week 16 |
-2
|
| Participant 4: Change at Week 56 |
-1
|
| Participant 5: Change at Week 16 |
1
|
| Participant 5: Change at Week 56 |
1
|
| Title | Change From Baseline in Stool Frequency Sub-Score of the Partial Mayo Score at Week 16 and Week 56 in UC Participants |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 16 and Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint and 'n' (number analyzed) signifies number of participants analyzed at specified timepoints. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 1 |
| Change at Week 16 |
-2
|
| Title | Change From Baseline in Rectal Bleeding Sub-Scores of the Partial Mayo Score at Week 16 and Week 56 in UC Participants |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 16 and Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint and 'n' (number analyzed) signifies number of participants analyzed at specified timepoints. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 1 |
| Change at Week 16 |
0
|
| Title | Change From Baseline in Abdominal Pain Using the Wong-Baker FACES Scale at Week 16 and Week 56 in UC Participants |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 16 And Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint and 'n' (number analyzed) signifies number of participants analyzed at specified timepoints. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 1 |
| Change at Week 16 |
-4
|
| Title | Change From Baseline in Absolute Stool Frequency at Week 16 and Week 56 in UC Participants |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 16 And Week 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received at least one infusion of infliximab after enrollment. Here 'N' (number of participants analyzed) signifies the number of participants for whom data was available for this endpoint and 'n' (number analyzed) signifies number of participants analyzed at specified timepoints. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 1 |
| Change at Week 16 |
-6
|
| Title | Correlation of Wong-Baker FACES Scale With Clinical Remission and Response at Week 16 |
|---|---|
| Description | 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. |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As the study was terminated early with lesser participants and lesser sample size, data for this OM was not collected. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 0 |
| Title | Relationship Between Abdominal Pain PCDAI Sub-Score And the Wong-Baker Faces Scale For CD Participants |
|---|---|
| Description | 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. |
| Time Frame | Week 16 and 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As the study was terminated early with lesser participants and lesser sample size, data for this OM was not collected. |
| Arm/Group Title | Dose Escalation Group |
|---|---|
| Arm/Group Description | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | Up to Week 64 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The safety analysis population included all participants who received at least one infusion of infliximab after enrollment. Reference arm was planned only for safety analysis in participants being treated with labeled dosing of infliximab. One participants who had crossed-over from reference group to Dose escalation group was counted in both arms and safety is presented accordingly. | |||
| Arm/Group Title | Reference Group | Dose Escalation Group | ||
| Arm/Group Description | Participants received infliximab 5 mg/kg intravenous (IV) infusion every 8 weeks (q8wk) up to 56 weeks with a final safety visit at Week 64. Those who lost clinical response during participation in the study were eligible to cross over to the Dose Escalation Group and receive a total of 56 weeks of therapy with infliximab, which included duration of therapy while in the Reference Group prior to dose escalation. | Participants received infliximab 10 mg/kg IV infusion q8wk from Week 0 to 56 with a final safety visit at Week 64. | ||
All Cause Mortality |
||||
| Reference Group | Dose Escalation Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/45 (0%) | 0/9 (0%) | ||
Serious Adverse Events |
||||
| Reference Group | Dose Escalation Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/45 (4.4%) | 1/9 (11.1%) | ||
| Gastrointestinal disorders | ||||
| Colitis Ulcerative | 0/45 (0%) | 1/9 (11.1%) | ||
| Infections and infestations | ||||
| Gastroenteritis Viral | 1/45 (2.2%) | 0/9 (0%) | ||
| Pharyngitis Streptococcal | 1/45 (2.2%) | 0/9 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Reference Group | Dose Escalation Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 36/45 (80%) | 8/9 (88.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/45 (0%) | 1/9 (11.1%) | ||
| Cardiac disorders | ||||
| Palpitations | 1/45 (2.2%) | 0/9 (0%) | ||
| Eye disorders | ||||
| Dry Eye | 0/45 (0%) | 1/9 (11.1%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 2/45 (4.4%) | 2/9 (22.2%) | ||
| Abdominal Pain Upper | 1/45 (2.2%) | 0/9 (0%) | ||
| Anorectal Disorder | 1/45 (2.2%) | 0/9 (0%) | ||
| Colitis Ulcerative | 1/45 (2.2%) | 2/9 (22.2%) | ||
| Constipation | 2/45 (4.4%) | 0/9 (0%) | ||
| Diarrhoea | 5/45 (11.1%) | 0/9 (0%) | ||
| Epigastric Discomfort | 1/45 (2.2%) | 0/9 (0%) | ||
| Faeces Soft | 1/45 (2.2%) | 0/9 (0%) | ||
| Gastritis | 1/45 (2.2%) | 0/9 (0%) | ||
| Haematochezia | 1/45 (2.2%) | 1/9 (11.1%) | ||
| Lip Swelling | 1/45 (2.2%) | 0/9 (0%) | ||
| Mouth Haemorrhage | 1/45 (2.2%) | 0/9 (0%) | ||
| Nausea | 2/45 (4.4%) | 0/9 (0%) | ||
| Stomatitis | 1/45 (2.2%) | 0/9 (0%) | ||
| Tongue Erythema | 1/45 (2.2%) | 0/9 (0%) | ||
| Tooth Disorder | 1/45 (2.2%) | 0/9 (0%) | ||
| Tooth Impacted | 1/45 (2.2%) | 0/9 (0%) | ||
| Toothache | 1/45 (2.2%) | 0/9 (0%) | ||
| Vomiting | 1/45 (2.2%) | 0/9 (0%) | ||
| General disorders | ||||
| Chest Discomfort | 1/45 (2.2%) | 0/9 (0%) | ||
| Chest Pain | 1/45 (2.2%) | 0/9 (0%) | ||
| Fatigue | 2/45 (4.4%) | 0/9 (0%) | ||
| Pain | 1/45 (2.2%) | 0/9 (0%) | ||
| Pyrexia | 1/45 (2.2%) | 0/9 (0%) | ||
| Immune system disorders | ||||
| Allergy to Arthropod Bite | 1/45 (2.2%) | 0/9 (0%) | ||
| Food Allergy | 1/45 (2.2%) | 0/9 (0%) | ||
| Infections and infestations | ||||
| Adenovirus Infection | 1/45 (2.2%) | 0/9 (0%) | ||
| Cellulitis | 1/45 (2.2%) | 0/9 (0%) | ||
| Clostridium Difficile Infection | 0/45 (0%) | 1/9 (11.1%) | ||
| Conjunctivitis | 1/45 (2.2%) | 0/9 (0%) | ||
| Ear Infection | 3/45 (6.7%) | 0/9 (0%) | ||
| Eczema Infected | 1/45 (2.2%) | 0/9 (0%) | ||
| Epstein-Barr Virus Infection | 1/45 (2.2%) | 0/9 (0%) | ||
| Eye Infection | 1/45 (2.2%) | 0/9 (0%) | ||
| Folliculitis | 2/45 (4.4%) | 0/9 (0%) | ||
| Gastroenteritis | 1/45 (2.2%) | 1/9 (11.1%) | ||
| Gingivitis | 1/45 (2.2%) | 0/9 (0%) | ||
| Herpes Zoster | 1/45 (2.2%) | 0/9 (0%) | ||
| Impetigo | 2/45 (4.4%) | 0/9 (0%) | ||
| Influenza | 0/45 (0%) | 2/9 (22.2%) | ||
| Nasopharyngitis | 5/45 (11.1%) | 0/9 (0%) | ||
| Otitis Media | 1/45 (2.2%) | 0/9 (0%) | ||
| Paronychia | 1/45 (2.2%) | 0/9 (0%) | ||
| Pharyngitis Streptococcal | 2/45 (4.4%) | 0/9 (0%) | ||
| Pneumonia | 1/45 (2.2%) | 0/9 (0%) | ||
| Sinusitis | 3/45 (6.7%) | 0/9 (0%) | ||
| Staphylococcal Impetigo | 1/45 (2.2%) | 0/9 (0%) | ||
| Upper Respiratory Tract Infection | 3/45 (6.7%) | 0/9 (0%) | ||
| Urinary Tract Infection | 2/45 (4.4%) | 0/9 (0%) | ||
| Viral Infection | 2/45 (4.4%) | 1/9 (11.1%) | ||
| Viral Upper Respiratory Tract Infection | 4/45 (8.9%) | 0/9 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Animal Bite | 1/45 (2.2%) | 0/9 (0%) | ||
| Burns Second Degree | 1/45 (2.2%) | 0/9 (0%) | ||
| Joint Dislocation | 1/45 (2.2%) | 0/9 (0%) | ||
| Joint Injury | 2/45 (4.4%) | 1/9 (11.1%) | ||
| Ligament Sprain | 2/45 (4.4%) | 0/9 (0%) | ||
| Limb Injury | 2/45 (4.4%) | 0/9 (0%) | ||
| Lip Injury | 0/45 (0%) | 1/9 (11.1%) | ||
| Soft Tissue Injury | 1/45 (2.2%) | 0/9 (0%) | ||
| Investigations | ||||
| Aspartate Aminotransferase Increased | 1/45 (2.2%) | 0/9 (0%) | ||
| C-Reactive Protein Increased | 2/45 (4.4%) | 0/9 (0%) | ||
| Faecal Calprotectin Increased | 1/45 (2.2%) | 0/9 (0%) | ||
| Heart Rate Irregular | 1/45 (2.2%) | 0/9 (0%) | ||
| Hepatic Enzyme Increased | 1/45 (2.2%) | 1/9 (11.1%) | ||
| Transaminases Increased | 1/45 (2.2%) | 0/9 (0%) | ||
| Vitamin D Decreased | 1/45 (2.2%) | 0/9 (0%) | ||
| White Blood Cell Count Increased | 0/45 (0%) | 1/9 (11.1%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 0/45 (0%) | 1/9 (11.1%) | ||
| Vitamin D Deficiency | 1/45 (2.2%) | 0/9 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 4/45 (8.9%) | 0/9 (0%) | ||
| Back Pain | 1/45 (2.2%) | 0/9 (0%) | ||
| Costochondritis | 1/45 (2.2%) | 0/9 (0%) | ||
| Neck Pain | 1/45 (2.2%) | 0/9 (0%) | ||
| Pain in Extremity | 1/45 (2.2%) | 1/9 (11.1%) | ||
| Synovial Cyst | 1/45 (2.2%) | 0/9 (0%) | ||
| Torticollis | 1/45 (2.2%) | 0/9 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Skin Papilloma | 1/45 (2.2%) | 0/9 (0%) | ||
| Nervous system disorders | ||||
| Dizziness Postural | 1/45 (2.2%) | 0/9 (0%) | ||
| Headache | 6/45 (13.3%) | 1/9 (11.1%) | ||
| Hemianopia | 1/45 (2.2%) | 0/9 (0%) | ||
| Lethargy | 1/45 (2.2%) | 0/9 (0%) | ||
| Migraine | 1/45 (2.2%) | 0/9 (0%) | ||
| Paraesthesia | 1/45 (2.2%) | 0/9 (0%) | ||
| Syncope | 2/45 (4.4%) | 0/9 (0%) | ||
| Psychiatric disorders | ||||
| Anxiety | 2/45 (4.4%) | 0/9 (0%) | ||
| Depression | 1/45 (2.2%) | 0/9 (0%) | ||
| Insomnia | 0/45 (0%) | 1/9 (11.1%) | ||
| Renal and urinary disorders | ||||
| Hydronephrosis | 1/45 (2.2%) | 0/9 (0%) | ||
| Reproductive system and breast disorders | ||||
| Ovarian Cyst | 1/45 (2.2%) | 0/9 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma Exercise Induced | 1/45 (2.2%) | 0/9 (0%) | ||
| Cough | 2/45 (4.4%) | 1/9 (11.1%) | ||
| Dyspnoea | 3/45 (6.7%) | 0/9 (0%) | ||
| Dyspnoea Exertional | 1/45 (2.2%) | 0/9 (0%) | ||
| Epistaxis | 2/45 (4.4%) | 1/9 (11.1%) | ||
| Nasal Congestion | 3/45 (6.7%) | 0/9 (0%) | ||
| Oropharyngeal Pain | 3/45 (6.7%) | 1/9 (11.1%) | ||
| Respiratory Tract Congestion | 1/45 (2.2%) | 0/9 (0%) | ||
| Rhinorrhoea | 1/45 (2.2%) | 0/9 (0%) | ||
| Tonsillolith | 1/45 (2.2%) | 0/9 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acne Cystic | 1/45 (2.2%) | 0/9 (0%) | ||
| Blister | 1/45 (2.2%) | 0/9 (0%) | ||
| Dry Skin | 1/45 (2.2%) | 0/9 (0%) | ||
| Psoriasis | 2/45 (4.4%) | 0/9 (0%) | ||
| Rash | 1/45 (2.2%) | 0/9 (0%) | ||
| Skin Warm | 0/45 (0%) | 1/9 (11.1%) | ||
| Vascular disorders | ||||
| Flushing | 1/45 (2.2%) | 0/9 (0%) | ||
| Orthostatic Hypertension | 1/45 (2.2%) | 0/9 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
| Name/Title | Director |
|---|---|
| Organization | Janssen Scientific Affairs |
| Phone | 844-434-4210 |
| ClinicalTrialDisclosure@its.jnj.com |
- CR108044
- C0168IBD4020
- 2015-001653-32