Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02318667
Recruitment Status : Completed
First Posted : December 17, 2014
Results First Posted : August 20, 2018
Last Update Posted : June 24, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Biological: Golimumab Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: 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.
Actual Study Start Date : February 27, 2015
Actual Primary Completion Date : June 21, 2017
Actual Study Completion Date : September 5, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Golimumab

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 Name: SIMPONI




Primary Outcome Measures :
  1. Serum ST2 Level at Week 6 [ Time Frame: 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.

  2. Correlation of Serum Soluble ST2 Levels With Endoscopic Activity of Disease (Assessed by Endoscopy Subscore of Mayo Score) at Week 6 [ Time Frame: 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.

  3. Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 6 [ Time Frame: 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.


Secondary Outcome Measures :
  1. Serum ST2 Level at Week 16 [ Time Frame: 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.

  2. Correlation of Serum Soluble ST2 Levels With Endoscopic Activity (Assessed by Endoscopy Subscore of Mayo Score) at Week 16 [ Time Frame: 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.

  3. Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 16 [ Time Frame: 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.

  4. Correlation of Serum Soluble ST2 Levels With Faecal Calprotectin Levels at Baseline and Week 6 and Week 16 [ Time Frame: 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.

  5. Correlation of Serum Soluble ST2 Levels With Clinical Activity (Assessed by Total Mayo Score) at Week 6 and Week 16 [ Time Frame: 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.

  6. Change From Baseline to Week 6 in ST2 Levels in Participants With Active Versus Inactive UC [ Time Frame: 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.

  7. 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) [ Time Frame: 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.

  8. Correlation of Endoscopic Mayo Subscore With Ulcerative Colitis Endoscopic Index Of Severity (UCEIS©) Overall Score at Week 6 and Week 16 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02318667


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:

Publications of Results:
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02318667     History of Changes
Other Study ID Numbers: 8259-022
2014-003262-25 ( EudraCT Number )
MK-8259-022 ( Other Identifier: Merck Protocol Number )
First Posted: December 17, 2014    Key Record Dates
Results First Posted: August 20, 2018
Last Update Posted: June 24, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
Layout table for MeSH terms
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs