Biomarkers of Intestinal Mucosal Healing in Crohn's Disease (P08143)

NCT01349920 | Completed Results

• 3 other identifiers: P081432011-000517-40MK-2155-195
• Study Type: observational
• Target: 15
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Crohn Disease

Keywords

biological markers; endoscopy; gastrointestinal

Outcome Measures

Primary Outcomes (11)

• Change From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6

  CDEIS endoscopically assesses mucosal status, by summing the following six component scores: number of bowel segments with deep ulcerations divided by number of visualized bowel segments; number of bowel segments with superficial ulcerations divided by number of visualized bowel segments; mean proportion of bowel segment surface involved by disease measured on 0-10 cm visual analog scale (VAS); mean proportion of bowel segment surface area involved by ulcerations measured on 0-10 cm VAS; presence of ulcerated stenosis anywhere; and presence of non-ulcerated stenosis anywhere. An observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy scored the CDEIS. The sum of the six components can range from 0-44, with a higher sum indicating greater severity of mucosal inflammation. Change from baseline is defined as Week 6 minus baseline CDEIS scores, with a negative change from baseline indicating improvement.

  Baseline and Week 6

• Change From Baseline in CDEIS Blinded Score at Week 22

  CDEIS endoscopically assesses mucosal status, by summing the following six component scores: number of bowel segments with deep ulcerations divided by number of visualized bowel segments; number of bowel segments with superficial ulcerations divided by number of visualized bowel segments; mean proportion of bowel segment surface involved by disease measured on 0-10 cm visual analog scale (VAS); mean proportion of bowel segment surface area involved by ulcerations measured on 0-10 cm VAS; presence of ulcerated stenosis anywhere; and presence of non-ulcerated stenosis anywhere. An observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy scored the CDEIS. The sum of the six components can range from 0-44, with a higher sum indicating greater severity of mucosal inflammation. Change from baseline is defined as Week 22 minus baseline CDEIS scores, with a negative change from baseline indicating improvement.

  Baseline and Week 22

• Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at Week 6

  Concentrations of the serum biomarker hsCRP were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline.

  Baseline and Week 6

• Change From Baseline in Serum hsCRP at Week 22

  Concentrations of the serum biomarker hsCRP were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline.

  Baseline and Week 22

• Change From Baseline in Stool Calprotectin at Week 6

  Concentrations of the stool biomarker calprotectin were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline.

  Baseline and Week 6

• Change From Baseline in Stool Calprotectin at Week 22

  Concentrations of the stool biomarker calprotectin were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline.

  Baseline and Week 22

• Change From Baseline in Serum Lipocalin-2 at Week 6

  Concentrations of the serum biomarker lipocalin-2 were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline.

  Baseline and Week 6

• Change From Baseline in Serum Lipocalin-2 at Week 22

  Concentrations of the serum biomarker lipocalin-2 were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline.

  Baseline and Week 22

• Change From Baseline in Regenerating Islet-Derived 3-Alpha (REG3-A) at Week 6

  Concentrations of the serum biomarker REG3-A were determined at baseline and at Week 6. The change from baseline was Week 6 minus baseline.

  Baseline and Week 6

• Change From Baseline in REG3-A at Week 22

  Concentrations of the serum biomarker REG3-A were determined at baseline and at Week 22. The change from baseline was Week 22 minus baseline.

  Baseline and Week 22

• 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

  To determine R\^2 a multiple linear regression analysis was conducted with the change from baseline in CDEIS score as the response variable and the baseline CDEIS score, changes from baseline in the four biomarkers serum hsCRP, serum lipocalin-2, serum Reg3-A, and stool calprotectin (their concentrations were log-transformed to make the mean function of the response more linear) at Weeks 6 and 22 as the predictor variables. CDEIS scores were provided by a blinded observer who viewed procedural videotape while blinded to the allocation number and visit of the endoscopy. The R\^2 can range from 0 to 1; with higher values indicating greater predictability of the model. The primary hypothesis is that the true R\^2 at weeks 6 and 22 is approximately 0.7.

  Baseline and Week 6 or 22

Secondary Outcomes (2)

• Concordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers

  Baseline Visit 1 (one week prior to dosing), Baseline Visit 2 (1-2 days prior to dosing)

• Concordance Correlation Coefficient for Comparison Between Central Endoscopic Evaluation and Site Endoscopic Evaluation

  Baseline, Week 6, Week 22

Study Arms (1)

Infliximab 5 mg/kg

Infliximab treatment and endoscopy.

Drug: Infliximab

Interventions

Infliximab DRUG

Infliximab administered intravenously at a dose of 5 mg/kg at study Weeks 0, 2, 6, 14, and 22.

Also known as: Remicade, SCH 215596, MK-2155

Infliximab 5 mg/kg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Biospecimen

Retention: SAMPLES WITH DNA

stool, serum, peripheral blood mononuclear cells (PBMC)

MeSH Terms

Conditions

Crohn Disease

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2011
• First Posted: May 9, 2011
• Study Start: November 28, 2012
• Primary Completion: September 28, 2015
• Study Completion: September 28, 2015
• Last Updated: October 15, 2018
• Results First Posted: September 28, 2016

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share