ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02566889
Recruitment Status : Recruiting
First Posted : October 2, 2015
Last Update Posted : May 31, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Scientific Affairs, LLC

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
Inflammatory Bowel Diseases Drug: Infliximab 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 12, 2015
Estimated Primary Completion Date : August 6, 2029
Estimated Study Completion Date : August 6, 2030


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 Name: 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 Name: Remicade




Primary Outcome Measures :
  1. Change From Baseline in Clinical Response at Week 16 After Dose Escalation [ Time Frame: Baseline and Week 16 After Dose Escalation ]
    Clinical response is defined as, Crohn's disease (CD) participants: A decrease from baseline in Pediatric Crohn's Disease Activity Index (PCDAI) of greater than or equal to (>=) 15 points with total score of less than or equal to (<=) 30 points. Ulcerative colitis (UC) participants: A decrease from baseline in partial Mayo score of >= 2 points and >= 30 percent (%) and a decrease in the rectal bleeding sub-score by >= 1 point or achievement of an absolute sub-score of <= 1 point.


Secondary Outcome Measures :
  1. Sustained Clinical Response Through 56 Weeks After Dose Escalation [ Time Frame: Baseline and Week 56 After Dose Escalation ]
    Sustained clinical response at Week 56 is defined as achieving clinical response per the primary endpoint definitions at Week 16 and maintaining clinical response at 1 year after dose escalation (Week 56).

  2. Relationship Between Trough Levels of Infliximab and Clinical Remission at Week 16 [ Time Frame: Week 16 ]
    The relationship between trough infliximab serum levels and clinical remission at Week 16 will be analyzed with the Reference Group and the Dose Escalation Group participants in a combined analysis.

  3. Change From Baseline at Week 16 and at Week 56 in Abdominal Pain and Loose/Watery Stool Frequency Sub-Scores of the Pediatric Crohn's Disease Activity Index (PCDAI) in Crohn's Disease (CD) Participants [ Time Frame: Baseline, Week 16 and Week 56 ]
    Abdominal and loose/watery stool frequency will be evaluated by using the relevant sub-scores of the PCDAI.

  4. Change From Baseline at Week 16 and at Week 56 in Stool Frequency and Rectal Bleeding Sub-Scores of the Partial Mayo Score for Ulcerative Colitis (UC) Participants [ Time Frame: Baseline, Week 16 and Week 56 ]
    Stool frequency and rectal bleeding will be evaluated by using the relevant sub-scores of partial Mayo score.

  5. Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Screening up to follow-up (8 weeks after the Last Dose Administration of Study Drug) ]
    A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  6. Changes from baseline at Week 16 and at Week 56 in Abdominal pain using the Wong-Baker FACES scale in CD Participants [ Time Frame: Baseline, Week 16 and Week 56 ]
    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.

  7. Changes from Baseline at Week 16 and at Week 56 in Absolute stool frequency in CD Participants [ Time Frame: Baseline, Week 16 and Week 56 ]
  8. Changes from Baseline at Week 16 and at Week 56 in Abdominal Pain Using the Wong-Baker FACES scale for UC Participants [ Time Frame: Baseline, Week 16 and Week 56 ]
    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.

  9. Changes from Baseline at Week 16 and at Week 56 in Absolute stool frequency in UC Participants [ Time Frame: Baseline, Week 16 and Week 56 ]
  10. Percentage of Participants who Achieved Clinical Response at Week 16 as assessed by Wong-Baker FACES Pain Scale [ Time Frame: 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 3.4 The scale shows a series of faces ranging from a happy face at 0, "No hurt" to a crying face at 10 "Hurts worst".

  11. Percentage of Participants who Achieved Clinical Remission at Week 16 as assessed by Wong-Baker FACES Pain Scale [ Time Frame: 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 3.4 The scale shows a series of faces ranging from a happy face at 0, "No hurt" to a crying face at 10 "Hurts worst".

  12. Association Between Abdominal Pain PCDAI Sub-Score and the Wong-Baker FACES Scale for CD Participants [ Time Frame: Up to 56 weeks ]
    The association between abdominal pain PCDAI sub-score and the Wong-Baker FACES scale for CD participants will be analysed using an ordinary regression model.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   6 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02566889


Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 51 Study Locations
Sponsors and Collaborators
Janssen Scientific Affairs, LLC
Investigators
Study Director: Janssen Scientific Affairs, LLC Clinical Trial Janssen Scientific Affairs, LLC

Additional Information:
Responsible Party: Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier: NCT02566889     History of Changes
Other Study ID Numbers: CR108044
C0168IBD4020 ( Other Identifier: Janssen Scientific Affairs, LLC )
2015-001653-32 ( EudraCT Number )
First Posted: October 2, 2015    Key Record Dates
Last Update Posted: May 31, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Scientific Affairs, LLC:
Pediatric Inflammatory Bowel Disease
Infliximab
Pediatric Participants
Pediatric Ulcerative Colitis
Pediatric Crohn's Disease
Dose Escalation

Additional relevant MeSH terms:
Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Infliximab
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents