Clinical trial NCT01349920: Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (P08143)
Official title: An Open Label Study to Discover Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (CD)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Crohn Disease
Keywords: biological markers
endoscopy
gastrointestinal
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-05-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Approximately 20 participants aged 18 to 60 years with Crohn's Disease will be enrolled from gastrointestinal specialist clinics.

Brief summary: This study will evaluate biomarkers that reflect changes in gut mucosal status during therapy with infliximab and determine whether changes in the levels of the selected biomarkers can be used to predict endoscopically assessed gut mucosal status changes.


Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of Crohn's Disease (CD) of at least 6 weeks duration, or acute diagnosis of sufficiently severe CD warranting initiation of infliximab sooner than allowed by fecal calprotectin turnaround time
* History of colonic involvement verified by prior endoscopy or radiography
* Indicated for treatment with infliximab according to current best medical practice
* Body Mass Index (BMI) between 15 kg/m\^2 and 35 kg/m\^2
* Women of childbearing potential and non-vasectomized men agree to use medically-acceptable contraception
* Negative pregnancy test
* No signs or symptoms of active tuberculosis (TB) and has a negative TB test within 6 weeks of first study drug administration

Exclusion Criteria:

* Pregnancy, intention to become pregnant, or breastfeeding
* Evidence of a colon unaffected by CD
* Indication for surgery
* Perianal disease likely to interfere with study participation
* Presence of a stoma or history of colectomy
* Symptomatic diarrhea unrelated to CD
* Strictures or evidence of bowel obstruction
* Presence of abscess unless completed definitive treatment can be documented one week prior to screening
* Presence of fistulas
* Contraindication to infliximab
* Intolerance to sedatives or other medications required for endoscopy
* Any prior use of anti-inflammatory biologic therapy
* Moderate or severe congestive heart failure
* History of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis
* Major surgery or donation/loss of at least one unit of blood within 4 weeks of screening
* Positive for hepatitis B surface antigen, hepatitis C antibodies, or Human Immunodeficiency Virus (HIV)
* History of any tumor except adequately treated basal cell carcinoma or carcinoma in situ of the cervix
* History of systemic granulomatous infection
* History of nontuberculous mycobacterial disease, or any opportunistic infection within 12 months of study entry
* Transplanted organ including bone marrow or hematopoietic stem cell-derived marrow

Primary outcomes:
measure: Change From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6
timeFrame: Baseline and Week 6
measure: Change From Baseline in CDEIS Blinded Score at Week 22
timeFrame: Baseline and Week 22
measure: Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at Week 6
timeFrame: Baseline and Week 6
measure: Change From Baseline in Serum hsCRP at Week 22
timeFrame: Baseline and Week 22
measure: Change From Baseline in Stool Calprotectin at Week 6
timeFrame: Baseline and Week 6
measure: Change From Baseline in Stool Calprotectin at Week 22
timeFrame: Baseline and Week 22
measure: Change From Baseline in Serum Lipocalin-2 at Week 6
timeFrame: Baseline and Week 6
measure: Change From Baseline in Serum Lipocalin-2 at Week 22
timeFrame: Baseline and Week 22
measure: Change From Baseline in Regenerating Islet-Derived 3-Alpha (REG3-A) at Week 6
timeFrame: Baseline and Week 6
measure: Change From Baseline in REG3-A at Week 22
timeFrame: Baseline and Week 22
measure: Coefficient of Determination (R^2) For Predicting The Change From Baseline In Blinded CDEIS Score From The Changes From Baseline In Four Biomarkers At Weeks 6 and 22
timeFrame: Baseline and Week 6 or 22
Secondary outcomes:
measure: Concordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers
timeFrame: Baseline Visit 1 (one week prior to dosing), Baseline Visit 2 (1-2 days prior to dosing)
measure: Concordance Correlation Coefficient for Comparison Between Central Endoscopic Evaluation and Site Endoscopic Evaluation
timeFrame: Baseline, Week 6, Week 22
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: