NCT01349920

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

Completed Results posted Last updated 15 October 2018

What this trial tests

trial testing Infliximab in Crohn Disease in 15 participants. Completed in 28 September 2015.

Timeline

28 November 2012

Primary endpoint
28 September 2015

28 September 2015

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Status	Completed
Study type	OBSERVATIONAL
Enrollment	15
Start date	28 November 2012
Primary completion	28 September 2015
Estimated completion	28 September 2015

Drugs / interventions tested

• Infliximab (infliximab) — full drug profile →

Conditions studied

• Crohn Disease — all drugs for Crohn Disease →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 60, any sex, with Crohn Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Infliximab 5 mg/kg	-4.8	± 4.2

Change From Baseline in CDEIS Blinded Score at Week 22 Primary · Baseline and 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 v

Group	Value	95% CI
Infliximab 5 mg/kg	-7.3	± 5.5

Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at Week 6 Primary · Baseline and 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.

Group	Value	95% CI
Infliximab 5 mg/kg	-38.1	± 30.4

Change From Baseline in Serum hsCRP at Week 22 Primary · Baseline and 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.

Group	Value	95% CI
Infliximab 5 mg/kg	-28.0	± 39.3

Change From Baseline in Stool Calprotectin at Week 6 Primary · Baseline and 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.

Group	Value	95% CI
Infliximab 5 mg/kg	231.1	± 4099.6

Change From Baseline in Stool Calprotectin at Week 22 Primary · Baseline and 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.

Group	Value	95% CI
Infliximab 5 mg/kg	98.3	± 3236.7

Change From Baseline in Serum Lipocalin-2 at Week 6 Primary · Baseline and 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.

Group	Value	95% CI
Infliximab 5 mg/kg	-103.7	± 108.3

Change From Baseline in Serum Lipocalin-2 at Week 22 Primary · Baseline and 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.

Group	Value	95% CI
Infliximab 5 mg/kg	-104.6	± 108.9

Change From Baseline in Regenerating Islet-Derived 3-Alpha (REG3-A) at Week 6 Primary · Baseline and 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.

Group	Value	95% CI
Infliximab 5 mg/kg	-20.7	± 20.9

Change From Baseline in REG3-A at Week 22 Primary · Baseline and 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.

Group	Value	95% CI
Infliximab 5 mg/kg	-21.2	± 30.3

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 Primary · Baseline and Week 6 or 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

Week 6 (n = 9)

Group	Value	95% CI
Infliximab 5 mg/kg	0.920	0.458 – 0.929

Week 22 (n = 10)

Group	Value	95% CI
Infliximab 5 mg/kg	0.638	0.539 – 0.946

Concordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers Secondary · Baseline Visit 1 (one week prior to dosing), Baseline Visit 2 (1-2 days prior to dosing)

Based on two measurements at baseline, the concordance correlation coefficient (CCC) was computed for each of four biomarkers, using a mixed effects model with a fixed factor for repeat measurements and a random factor for participant. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements.

serum hsCRP (n=14)

Group	Value	95% CI
Infliximab 5 mg/kg	0.954	0.913 – 0.995

serum REG3-A (n=15)

Group	Value	95% CI
Infliximab 5 mg/kg	0.974	0.952 – 0.996

serum lipocalin-2 (n=15)

Group	Value	95% CI
Infliximab 5 mg/kg	0.910	0.835 – 0.986

stool calprotectin (n=15)

Group	Value	95% CI
Infliximab 5 mg/kg	0.792	0.629 – 0.954

Adverse events — posted to ClinicalTrials.gov

Time frame: From 4 weeks prior to first dose, until 2 weeks after last dose (up to 28 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pre-study

Serious: 0/15 (0%)

Deaths: —

Infliximab 5mg/kg

Serious: 2/15 (13%)

Deaths: —

Post-study

Serious: 0/15 (0%)

Deaths: —

Serious adverse events (2 terms)

Reaction	System	Pre-study	Infliximab 5mg/kg	Post-study
Crohn's disease	Gastrointestinal disorders	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—

Other adverse events (42 terms — click to expand)

Reaction	System	Pre-study	Infliximab 5mg/kg	Post-study
Nasopharyngitis	Infections and infestations	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Gastroenteritis	Infections and infestations	—	—	—
Procedural hypotension	Injury, poisoning and procedural complications	—	—	—
Iron deficiency	Metabolism and nutrition disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Paraesthesia	Nervous system disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—
Eczema	Skin and subcutaneous tissue disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—	—
Eye irritation	Eye disorders	—	—	—
Eye pain	Eye disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Aphthous ulcer	Gastrointestinal disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—
Gastrointestinal sounds abnormal	Gastrointestinal disorders	—	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—	—
Axillary pain	General disorders	—	—	—
Non-cardiac chest pain	General disorders	—	—	—
Pain	General disorders	—	—	—
Conjunctivitis	Infections and infestations	—	—	—
Ear infection	Infections and infestations	—	—	—
Rhinitis	Infections and infestations	—	—	—
Tonsillitis	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Accidental overdose	Injury, poisoning and procedural complications	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Migraine	Nervous system disorders	—	—	—
Syncope	Nervous system disorders	—	—	—
Anxiety	Psychiatric disorders	—	—	—
Bladder pain	Renal and urinary disorders	—	—	—

Most-reported serious reactions: Crohn's disease, Infusion related reaction.

Data from ClinicalTrials.gov NCT01349920 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.