Trial Outcomes & Findings for Correlation of Soluble Suppression of Tumorigenicity 2 (ST2) With Golimumab (MK-8259) Response in Participants With Ulcerative Colitis (UC) (MK-8529-022). (NCT NCT02318667)

NCT ID: NCT02318667

Last Updated: 2021-01-27

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 38 participants
• Primary outcome timeframe: Week 6
• Results posted on: 2021-01-27

Participant Flow

Participant milestones

Measure	Golimumab Treatment Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.
Overall Study STARTED	38
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Measure	Golimumab Treatment Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	6
Overall Study Protocol Violation	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Golimumab Treatment n=38 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.
Age, Continuous	34.8 Years STANDARD_DEVIATION 12.15 • n=38 Participants
Sex: Female, Male Female	23 Participants n=38 Participants
Sex: Female, Male Male	15 Participants n=38 Participants
Serum human Suppression of Tumorigenicity 2 (ST2) level	21.8 ng/mL STANDARD_DEVIATION 11.09 • n=34 Participants • Participants with available ST2 data

PRIMARY outcome

Timeframe: Week 6

Population: Participants with available Week 6 ST2 data.

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.

Outcome measures

Measure	Golimumab Treatment n=34 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Serum ST2 Level at Week 6	21.8 ng/mL Standard Deviation 14.41	—

PRIMARY outcome

Timeframe: Week 6

Population: Analysis population includes all participants who had received study medication, had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and had a Week 6 endoscopic Mayo subscore.

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 between -0.5 to -0.3 or 0.3 to 0.5.

Outcome measures

Measure	Golimumab Treatment n=34 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Correlation of Serum Soluble ST2 Levels With Endoscopic Activity of Disease (Assessed by Endoscopy Subscore of Mayo Score) at Week 6	0.451 Spearman correlation (rs) coefficient Interval 0.133 to 0.685	—

PRIMARY outcome

Timeframe: Week 6

Population: Analysis population includes all participants who had received study medication, had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and had a Week 6 Geboes index score.

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.

Outcome measures

Measure	Golimumab Treatment n=34 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 6	0.252 rs coefficient Interval -0.094 to 0.544	—

SECONDARY outcome

Timeframe: Week 16

Population: Participants with available Week 16 ST2 data.

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.

Outcome measures

Measure	Golimumab Treatment n=29 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Serum ST2 Level at Week 16	17.9 ng/mL Standard Deviation 13.10	—

SECONDARY outcome

Timeframe: Week 16

Population: Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and had a Week 16 endoscopic Mayo subscore.

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 0.3 to 0.5.

Outcome measures

Measure	Golimumab Treatment n=29 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Correlation of Serum Soluble ST2 Levels With Endoscopic Activity (Assessed by Endoscopy Subscore of Mayo Score) at Week 16	0.268 rs coefficient Interval -0.109 to 0.578	—

SECONDARY outcome

Timeframe: Week 16

Population: Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and had a Week 16 Geboes index score.

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.

Outcome measures

Measure	Golimumab Treatment n=29 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 16	0.177 rs coefficient Interval -0.202 to 0.511	—

SECONDARY outcome

Timeframe: Baseline, Weeks 6 and 16

Population: Analysis population includes all participants who had received study medication and had a valid faecal calprotectin assessment at time point (Baseline, Week 6, and Week 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.

Outcome measures

Measure	Golimumab Treatment n=32 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Correlation of Serum Soluble ST2 Levels With Faecal Calprotectin Levels at Baseline and Week 6 and Week 16 Baseline	0.146 rs coefficient Interval -0.214 to 0.47	—
Correlation of Serum Soluble ST2 Levels With Faecal Calprotectin Levels at Baseline and Week 6 and Week 16 Week 6	-0.022 rs coefficient Interval -0.374 to 0.335	—
Correlation of Serum Soluble ST2 Levels With Faecal Calprotectin Levels at Baseline and Week 6 and Week 16 Week 16	-0.140 rs coefficient Interval -0.487 to 0.246	—

SECONDARY outcome

Timeframe: Weeks 6 and 16

Population: Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and total Mayo score at 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 coefficient between -0.5 to -0.3 or 0.3 to 0.5.

Outcome measures

Measure	Golimumab Treatment n=34 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Correlation of Serum Soluble ST2 Levels With Clinical Activity (Assessed by Total Mayo Score) at Week 6 and Week 16 Week 6	0.404 rs coefficient Interval 0.076 to 0.653	—
Correlation of Serum Soluble ST2 Levels With Clinical Activity (Assessed by Total Mayo Score) at Week 6 and Week 16 Week 16	0.098 rs coefficient Interval -0.279 to 0.448	—

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity at 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.

Outcome measures

Measure	Golimumab Treatment n=14 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease n=20 Participants Participants with active Ulcerative Colitis at Week 6
Change From Baseline to Week 6 in ST2 Levels in Participants With Active Versus Inactive UC Baseline	17.2 ng/mL Standard Deviation 6.81	25.0 ng/mL Standard Deviation 12.47
Change From Baseline to Week 6 in ST2 Levels in Participants With Active Versus Inactive UC Change from baseline at Week 6	-3.5 ng/mL Standard Deviation 6.89	2.4 ng/mL Standard Deviation 7.75

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Analysis population includes all participants who had received study medication and achieved endoscopic response at 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.

Outcome measures

Measure	Golimumab Treatment n=10 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease n=4 Participants Participants with active Ulcerative Colitis at Week 6
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) Baseline	15.7 ng/mL Standard Deviation 6.06	21.0 ng/mL Standard Deviation 8.01
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) Change from Baseline at Week 6	-1.8 ng/mL Standard Deviation 7.28	-7.8 ng/mL Standard Deviation 3.68

SECONDARY outcome

Timeframe: Week 6 and Week 16

Population: Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and UCEIS overall score at 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.

Outcome measures

Measure	Golimumab Treatment n=34 Participants Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.	Active Disease Participants with active Ulcerative Colitis at Week 6
Correlation of Endoscopic Mayo Subscore With Ulcerative Colitis Endoscopic Index Of Severity (UCEIS©) Overall Score at Week 6 and Week 16 Week 6	0.830 rs coefficient Interval 0.683 to 0.912	—
Correlation of Endoscopic Mayo Subscore With Ulcerative Colitis Endoscopic Index Of Severity (UCEIS©) Overall Score at Week 6 and Week 16 Week 16	0.875 rs coefficient Interval 0.748 to 0.94	—

Adverse Events

Golimumab Treatment

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Golimumab Treatment n=38 participants at risk Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.
Gastrointestinal disorders Colitis ulcerative	7.9% 3/38 • Number of events 4 • Up to 16 weeks Analysis population includes all participants who received at least one dose of study medication.
Infections and infestations Pneumonia	2.6% 1/38 • Number of events 1 • Up to 16 weeks Analysis population includes all participants who received at least one dose of study medication.

Other adverse events

Measure	Golimumab Treatment n=38 participants at risk Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks.
Gastrointestinal disorders Colitis ulcerative	10.5% 4/38 • Number of events 4 • Up to 16 weeks Analysis population includes all participants who received at least one dose of study medication.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial.
• Publication restrictions are in place

Restriction type: OTHER