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

An Open Label, Single Group Assignment Design Study to Correlate Soluble ST2 With Clinical, Endoscopic and Histological Activity in Moderate to Severe Ulcerative Colitis Patients Under Golimumab.

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.

Study Overview

• Status: Completed
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Biological: Golimumab

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inadequate response to conventional therapy including corticosteroids or are intolerant to, or have medical contraindications for conventional therapies
• UC diagnosed prior to screening, based on a biopsy collected at endoscopy
• Moderate to severe active UC with total Mayo score of 6 to 12, inclusive at baseline, and endoscopic Mayo sub-score, greater than or equal to 2
• Adenomatous polyps removed within last 5 years or at the screening visit prior to the first drug treatment
• Extensive colitis for ≥ 8 years, or disease limited to the left side of the colon for ≥10 years should have a colonoscopy to exclude the presence of dysplasia within 1 year prior to study inclusion or a colonoscopy to exclude the presence of malignancy at the screening visit
• No history of untreated latent or active Tuberculosis (TB) prior to screening
• Negative stool results for enteric pathogens

Exclusion Criteria:

• History of asthma
• History of autoimmune diseases
• History of hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Golimumab; Golimumab 50mg/0.5 mL in a single-use, ready-to-use autoinjector. Golimumab is a fully human anti-TNF (tumor necrosis factor) alpha monoclonal antibody that will be administered SC.; Other Names: SIMPONI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum ST2 Level at 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.	Week 6
Correlation of Serum Soluble ST2 Levels With Endoscopic Activity of Disease (Assessed by Endoscopy Subscore of Mayo Score) at 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 between -0.5 to -0.3 or 0.3 to 0.5.	Week 6
Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at 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.	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum ST2 Level at 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.	Week 16
Correlation of Serum Soluble ST2 Levels With Endoscopic Activity (Assessed by Endoscopy Subscore of Mayo Score) at 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 0.3 to 0.5.	Week 16
Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at 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.	Week 16
Correlation of Serum Soluble ST2 Levels With Faecal Calprotectin Levels at Baseline and 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.	Baseline, Weeks 6 and 16
Correlation of Serum Soluble ST2 Levels With Clinical Activity (Assessed by Total Mayo Score) at Week 6 and Week 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.	Weeks 6 and 16
Change From Baseline to Week 6 in ST2 Levels in Participants With Active Versus Inactive UC	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, 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)	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, Week 6
Correlation of Endoscopic Mayo Subscore With Ulcerative Colitis Endoscopic Index Of Severity (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.	Week 6 and Week 16

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Magro F, Lopes S, Silva M, Coelho R, Portela F, Branquinho D, Correia L, Fernandes S, Cravo M, Caldeira P, Sousa HT, Patita M, Lago P, Ramos J, Afonso J, Redondo I, Machado P, Cornillie F, Lopes J, Carneiro F; Portuguese IBD Group [GEDII]. Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study. J Crohns Colitis. 2019 Oct 28;13(11):1387-1393. doi: 10.1093/ecco-jcc/jjz071.
• Magro F, Lopes S, Silva M, Coelho R, Portela F, Branquinho D, Correia L, Fernandes S, Cravo M, Caldeira P, Tavares de Sousa H, Patita M, Lago P, Ramos J, Afonso J, Redondo I, Machado P, Philip G, Lopes J, Carneiro F. Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab. Therap Adv Gastroenterol. 2019 Aug 30;12:1756284819869141. doi: 10.1177/1756284819869141. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2015
• Primary Completion (Actual): June 21, 2017
• Study Completion (Actual): September 5, 2017

Study Registration Dates

• First Submitted: December 12, 2014
• First Submitted That Met QC Criteria: December 12, 2014
• First Posted (Estimate): December 17, 2014

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 7, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Golimumab
• Other Study ID Numbers: 8259-022; 2014-003262-25 (EudraCT Number); MK-8259-022 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf