NCT02318667: EVOLUTION

Correlation of Soluble Suppression of Tumorigenicity 2 (ST2) With Golimumab (MK-8259) Response in Participants With Ulcerative Colitis (UC) (MK-8529-022).

Completed Phase 4 Results posted Last updated 27 January 2021

What this trial tests

Phase 4 trial testing Golimumab in Colitis, Ulcerative in 38 participants. Completed in 5 September 2017.

Timeline

27 February 2015

Primary endpoint
21 June 2017

5 September 2017

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	38
Start date	27 February 2015
Primary completion	21 June 2017
Estimated completion	5 September 2017

Drugs / interventions tested

• Golimumab (GOLIMUMAB) — full drug profile →

Conditions studied

• Colitis, Ulcerative — all drugs for Colitis, Ulcerative →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 65, any sex, with Colitis, Ulcerative. 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.

Serum ST2 Level at Week 6 Primary · Week 6

ST2, a serum biomarker, was collected at Week 6. ST2 levels were used to determine whether or not there is a correlation with endoscopic or histologic activity, or a clinical response to treatment in participants with moderate to severe Ulcerative Colitis.

Group	Value	95% CI
Golimumab Treatment	21.8	± 14.41

Correlation of Serum Soluble ST2 Levels With Endoscopic Activity of Disease (Assessed by Endoscopy Subscore of Mayo Score) at Week 6 Primary · Week 6

ST2, a serum biomarker, was collected at Week 6. Endoscopic Mayo subscore is one of 4 components that comprise the total Mayo Score, a scale for assessing ulcerative colitis (UC) activity. Endoscopic Mayo subscore ranges from 0-3: 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). A higher score indicates more severe disease. Moderate correlation was defined as a Spearman correlation (rs) coefficient

Group	Value	95% CI
Golimumab Treatment	0.451	0.133 – 0.685

Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 6 Primary · Week 6

ST2, a serum biomarker, was collected at Week 6. Geboes index, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5.

Group	Value	95% CI
Golimumab Treatment	0.252	-0.094 – 0.544

Serum ST2 Level at Week 16 Secondary · Week 16

ST2, a serum biomarker, was collected at Week 16. ST2 levels were used to determine whether or not there is a correlation with endoscopic or histologic activity, or a clinical response to treatment in participants with moderate to severe Ulcerative Colitis.

Group	Value	95% CI
Golimumab Treatment	17.9	± 13.10

Correlation of Serum Soluble ST2 Levels With Endoscopic Activity (Assessed by Endoscopy Subscore of Mayo Score) at Week 16 Secondary · Week 16

ST2, a serum biomarker, was collected at Week 16. Endoscopic Mayo subscore is one of 4 components that comprise the total Mayo Score, a scale for assessing ulcerative colitis (UC) activity. Endoscopic Mayo subscore ranges from 0-3: 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or

Group	Value	95% CI
Golimumab Treatment	0.268	-0.109 – 0.578

Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 16 Secondary · Week 16

ST2, a serum biomarker, was collected at Week 16. Geboes index, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5.

Group	Value	95% CI
Golimumab Treatment	0.177	-0.202 – 0.511

Correlation of Serum Soluble ST2 Levels With Faecal Calprotectin Levels at Baseline and Week 6 and Week 16 Secondary · Baseline, Weeks 6 and 16

ST2 and faecal calprotectin, serum biomarkers, were collected at Week 6 and Week 16. Faecal calprotectin is a surrogate marker for the presence of intestinal inflammation and response to treatment in participants with Inflammatory Bowel Disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5.

Baseline

Group	Value	95% CI
Golimumab Treatment	0.146	-0.214 – 0.470

Week 6

Group	Value	95% CI
Golimumab Treatment	-0.022	-0.374 – 0.335

Week 16

Group	Value	95% CI
Golimumab Treatment	-0.140	-0.487 – 0.246

Correlation of Serum Soluble ST2 Levels With Clinical Activity (Assessed by Total Mayo Score) at Week 6 and Week 16 Secondary · Weeks 6 and 16

ST2, a serum biomarker, was collected at Week 6 and Week 16. The total Mayo Score, is a scale for assessing UC activity and is the sum of 4 subscores (assessment of stool frequency \[0-3\], rectal bleeding \[0-3\], Physician's Global Assessment \[0-3\], and endoscopic Mayo subscore \[0-3\]) and has values that range from 0 to 12. Clinical remission: ≤2 points with no individual subscore \> 1; Mildly active disease: 3-5 points; Moderately active disease: 6-10 points; Severely active disease: 11-12 points. A higher score indicates more severe disease. Moderate correlation was defined as rs coeff

Week 6

Group	Value	95% CI
Golimumab Treatment	0.404	0.076 – 0.653

Week 16

Group	Value	95% CI
Golimumab Treatment	0.098	-0.279 – 0.448

Change From Baseline to Week 6 in ST2 Levels in Participants With Active Versus Inactive UC Secondary · Baseline, Week 6

ST2, a serum biomarker, was collected at Baseline and Week 6. Active Ulcerative Colitis was defined as an endoscopic Mayo subscore ≥2 and inactive Ulcerative Colitis was defined as an endoscopic Mayo subscore of 0 or 1.

Baseline

Group	Value	95% CI
Inactive Disease	17.2	± 6.81
Active Disease	25.0	± 12.47

Change from baseline at Week 6

Group	Value	95% CI
Inactive Disease	-3.5	± 6.89
Active Disease	2.4	± 7.75

Change From Baseline to Week 6 in ST2 Level According to Participant's Mayo Endoscopic Response at Week 16 (Maintained Response at Week 16 or Did Not Maintain Response at Week 16) Secondary · Baseline, Week 6

ST2, a serum biomarker, was collected at Baseline and Week 6. Comparison of participants who achieved endoscopic response \[endoscopic Mayo subscore 0 or 1\] at Week 6 and maintained response through Week 16 versus participants who did not maintain response throughout Week 16, regarding serum soluble ST2 at baseline, Week 6 and change between baseline and Week 6.

Baseline

Group	Value	95% CI
Maintained Endoscopic Response	15.7	± 6.06
Did Not Maintain Endoscopic Response	21.0	± 8.01

Change from Baseline at Week 6

Group	Value	95% CI
Maintained Endoscopic Response	-1.8	± 7.28
Did Not Maintain Endoscopic Response	-7.8	± 3.68

Correlation of Endoscopic Mayo Subscore With Ulcerative Colitis Endoscopic Index Of Severity (UCEIS©) Overall Score at Week 6 and Week 16 Secondary · Week 6 and Week 16

UCEIS© is a 3-item (vascular pattern, bleeding and erosion/ulceration) validated tool for assessing endoscopic severity of UC. Each item has 3 or 4 levels of severity and is given a score. The scores for each individual item are combined into a total score ranging from 1 to 11. A higher score indicates increased endoscopic severity of UC. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5.

Week 6

Group	Value	95% CI
Golimumab Treatment	0.830	0.683 – 0.912

Week 16

Group	Value	95% CI
Golimumab Treatment	0.875	0.748 – 0.940

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 16 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Golimumab Treatment

Serious: 4/38 (11%)

Deaths: 0/38

Serious adverse events (2 terms)

Reaction	System	Golimumab Treatment
Colitis ulcerative	Gastrointestinal disorders	—
Pneumonia	Infections and infestations	—

Other adverse events (1 terms — click to expand)

Reaction	System	Golimumab Treatment
Colitis ulcerative	Gastrointestinal disorders	—

Most-reported serious reactions: Colitis ulcerative, Pneumonia.

Data from ClinicalTrials.gov NCT02318667 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate serum soluble human ST2 protein, the receptor for Interleukin-33 (IL-33) and a member of the proinflammatory Interleukin-1 (IL-1) receptor superfamily, as a surrogate biological marker predictive of disease outcome and therapeutic response to golimumab treatment in participants with moderate to severe UC who have failed on prior conventional therapies. The primary endpoints of this study are to correlate serum soluble ST2 levels with endoscopic activity (endoscopic subscore of the Mayo score) and histological activity (Geboes index) of disease.

Publications & conference data

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