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CompletedNCT01349920Updated Oct 15, 2018Results posted

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

An observational study in Crohn Disease, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2018-10-15.

Sponsored by Merck Sharp & Dohme LLC · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
15
Ages
18 Years to 60 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Crohn Disease

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Keywords

  • biological markers
  • endoscopy
  • gastrointestinal
03

In context

Crohn Disease

1,880 studies on the registry are indexed under Crohn Disease; 462 are open to participants now.

This study's enrollment of 15 is below the median of 162 across 608 observational studies indexed under Crohn Disease.

Browse Crohn Disease studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No
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.

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

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
05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
15 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • Infliximab 5 mg/kg

    Infliximab treatment and endoscopy.

    Drug: Infliximab

Interventions

  • DrugInfliximab

    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

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline and Week 6

  2. 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.

    Time frame: Baseline and Week 22

  3. 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.

    Time frame: Baseline and Week 6

  4. 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.

    Time frame: Baseline and Week 22

  5. 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.

    Time frame: Baseline and Week 6

  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.

    Time frame: Baseline and Week 22

  7. 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.

    Time frame: Baseline and Week 6

  8. 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.

    Time frame: Baseline and Week 22

  9. 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.

    Time frame: Baseline and Week 6

  10. 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.

    Time frame: Baseline and Week 22

  11. 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.

    Time frame: Baseline and Week 6 or 22

Secondary outcomes

  1. Concordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers

    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.

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

  2. Concordance Correlation Coefficient for Comparison Between Central Endoscopic Evaluation and Site Endoscopic Evaluation

    The CCC of blinded (central) versus unblinded (site) scores from either CDEIS or the Simple Endoscopic Score for Crohn's Disease (SES-CD) was determined at Baseline, Week 6 and Week 22. SES-CD sums the following scores: presence and size of ulcers in five visualized bowel segments; extent of ulcerated surface in five visualized bowel segments; extent of affected surface in five visualized bowel segments; presence and type of narrowings in five visualized bowel segments; and can range from 0-56, with a higher sum indicating greater severity of mucosal inflammation. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements.

    Time frame: Baseline, Week 6, Week 22

07

Results

Posted Sep 28, 2016

Participant flow

Participants 18 to 60 years of age, with moderate to severe Crohn's Disease (CD) who had not been previously treated with anti-inflammatory biologic agents were enrolled in this trial.

Participant flow — Overall Study
MilestoneInfliximab 5mg/kg
Started15
Completed15
Not completed0

Outcome measures

PrimaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · Score on a scale
Change From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6
Score on a scaleInfliximab 5 mg/kg
Change From Baseline in the Crohn's Disease Endoscopic Index of Severity (CDEIS) Blinded Score at Week 6-4.8 ± 4.2
PrimaryChange 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.

Time frame:
Baseline and Week 22
Reported as:
Mean · Score on a scale
Change From Baseline in CDEIS Blinded Score at Week 22
Score on a scaleInfliximab 5 mg/kg
Change From Baseline in CDEIS Blinded Score at Week 22-7.3 ± 5.5
PrimaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · mg/L
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at Week 6
mg/LInfliximab 5 mg/kg
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at Week 6-38.1 ± 30.4
PrimaryChange 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.

Time frame:
Baseline and Week 22
Reported as:
Mean · mg/L
Change From Baseline in Serum hsCRP at Week 22
mg/LInfliximab 5 mg/kg
Change From Baseline in Serum hsCRP at Week 22-28.0 ± 39.3
PrimaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · µg/g
Change From Baseline in Stool Calprotectin at Week 6
µg/gInfliximab 5 mg/kg
Change From Baseline in Stool Calprotectin at Week 6231.1 ± 4099.6
PrimaryChange 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.

Time frame:
Baseline and Week 22
Reported as:
Mean · µg/g
Change From Baseline in Stool Calprotectin at Week 22
µg/gInfliximab 5 mg/kg
Change From Baseline in Stool Calprotectin at Week 2298.3 ± 3236.7
PrimaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · ng/mL
Change From Baseline in Serum Lipocalin-2 at Week 6
ng/mLInfliximab 5 mg/kg
Change From Baseline in Serum Lipocalin-2 at Week 6-103.7 ± 108.3
PrimaryChange 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.

Time frame:
Baseline and Week 22
Reported as:
Mean · ng/mL
Change From Baseline in Serum Lipocalin-2 at Week 22
ng/mLInfliximab 5 mg/kg
Change From Baseline in Serum Lipocalin-2 at Week 22-104.6 ± 108.9
PrimaryChange 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.

Time frame:
Baseline and Week 6
Reported as:
Mean · ng/mL
Change From Baseline in Regenerating Islet-Derived 3-Alpha (REG3-A) at Week 6
ng/mLInfliximab 5 mg/kg
Change From Baseline in Regenerating Islet-Derived 3-Alpha (REG3-A) at Week 6-20.7 ± 20.9
PrimaryChange 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.

Time frame:
Baseline and Week 22
Reported as:
Mean · ng/mL
Change From Baseline in REG3-A at Week 22
ng/mLInfliximab 5 mg/kg
Change From Baseline in REG3-A at Week 22-21.2 ± 30.3
PrimaryCoefficient 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.

Time frame:
Baseline and Week 6 or 22
Reported as:
Number · Coefficient of Determination
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
Coefficient of DeterminationInfliximab 5 mg/kg
Week 6 (n = 9)0.920 (0.458 to 0.929)
Week 22 (n = 10)0.638 (0.539 to 0.946)
Statistical analysis
  • Infliximab 5 mg/kg · Multiple Linear Regression · p = 0.071
  • Infliximab 5 mg/kg · Multiple Linear Regression · p = 0.381
SecondaryConcordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers

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.

Time frame:
Baseline Visit 1 (one week prior to dosing), Baseline Visit 2 (1-2 days prior to dosing)
Reported as:
Number · Correlation coefficient
Concordance Correlation Coefficient for Comparison of Repeat Baseline Measurements of Biochemical Biomarkers
Correlation coefficientInfliximab 5 mg/kg
serum hsCRP (n=14)0.954 (0.913 to 0.995)
serum REG3-A (n=15)0.974 (0.952 to 0.996)
serum lipocalin-2 (n=15)0.910 (0.835 to 0.986)
stool calprotectin (n=15)0.792 (0.629 to 0.954)
SecondaryConcordance Correlation Coefficient for Comparison Between Central Endoscopic Evaluation and Site Endoscopic Evaluation

The CCC of blinded (central) versus unblinded (site) scores from either CDEIS or the Simple Endoscopic Score for Crohn's Disease (SES-CD) was determined at Baseline, Week 6 and Week 22. SES-CD sums the following scores: presence and size of ulcers in five visualized bowel segments; extent of ulcerated surface in five visualized bowel segments; extent of affected surface in five visualized bowel segments; presence and type of narrowings in five visualized bowel segments; and can range from 0-56, with a higher sum indicating greater severity of mucosal inflammation. The CCC can range from 0 to 1 with higher values indicating greater concordance between the 2 measurements.

Time frame:
Baseline, Week 6, Week 22
Reported as:
Number · Correlation coefficient
Concordance Correlation Coefficient for Comparison Between Central Endoscopic Evaluation and Site Endoscopic Evaluation
Correlation coefficientInfliximab 5 mg/kg
CDEIS Baseline (n = 15)0.662 (0.428 to 0.896)
CDEIS Week 6 (n = 13)0.693 (0.458 to 0.929)
CDEIS Week 22 (n = 12)0.743 (0.539 to 0.946)
SES-CD Baseline (n = 15)0.453 (0.176 to 0.729)
SES-CD Week 6 (n = 13)0.937 (0.879 to 0.995)
SES-CD Week 22 (n = 13)0.753 (0.562 to 0.945)

Adverse events

Collected over From 4 weeks prior to first dose, until 2 weeks after last dose (up to 28 weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Pre-study—0/15 (0%)7/15 (46.7%)
Infliximab 5mg/kg—2/15 (13.3%)13/15 (86.7%)
Post-study—0/15 (0%)0/15 (0%)
Most frequent serious events
Most frequent serious events
EventPre-studyInfliximab 5mg/kgPost-study
Crohn's diseaseGastrointestinal disorders0/151/150/15
Infusion related reactionInjury, poisoning and procedural complications0/151/150/15
Most frequent other events
Showing 10 of 42
Most frequent other events
EventPre-studyInfliximab 5mg/kgPost-study
NasopharyngitisInfections and infestations1/155/150/15
VomitingGastrointestinal disorders3/152/15—
Back painMusculoskeletal and connective tissue disorders0/153/150/15
HeadacheNervous system disorders0/153/150/15
NauseaGastrointestinal disorders0/152/150/15
GastroenteritisInfections and infestations0/152/150/15
Procedural hypotensionInjury, poisoning and procedural complications0/152/150/15
Iron deficiencyMetabolism and nutrition disorders2/150/150/15
ArthralgiaMusculoskeletal and connective tissue disorders0/152/150/15
ParaesthesiaNervous system disorders0/152/150/15

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Infliximab 5mg/kg
Mean25.0 ± 9.6
Sex: Female, Male
Sex: Female, Male(Participants)Infliximab 5mg/kg
Female7
Male8
08

Study locations

No study locations are listed for this record.

09

References and documents

Individual participant data

Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

No publications or documents are linked to this record.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 15, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01349920
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
May 9, 2011
Start date
Nov 28, 2012
Primary completion
Sep 28, 2015
Completion
Sep 28, 2015
Results posted
Sep 28, 2016
Last update
Oct 15, 2018

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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