Clinical Trial Results:
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.
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Summary
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EudraCT number |
2014-003262-25 |
Trial protocol |
PT |
Global end of trial date |
05 Sep 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Jun 2018
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First version publication date |
20 Jun 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MK-8259-022
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02318667 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Sep 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Sep 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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 Ulcerative Colitis (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.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Feb 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Portugal: 38
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Worldwide total number of subjects |
38
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EEA total number of subjects |
38
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
37
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
Participants with 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. | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Golimumab treatment | ||||||||||||||
Arm description |
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. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Golimumab
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Investigational medicinal product code |
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Other name |
MK-8259; Simponi
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Golimumab 50mg/0.5 mL in a single-use, ready-to-use autoinjector. Golimumab is a fully human anti-tumor
necrosis factor (anti-TNF) alpha monoclonal antibody that will be administered
SC.
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Baseline characteristics reporting groups
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Reporting group title |
Golimumab treatment
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Golimumab treatment
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Reporting group description |
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. | ||
Subject analysis set title |
Inactive disease
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with inactive Ulcerative Colitis at Week 6
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Subject analysis set title |
Active disease
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants with active Ulcerative Colitis at Week 6
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Subject analysis set title |
Maintained endoscopic response
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants who achieved endoscopic response at Week 6 and maintained endoscopic response at Week 16
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Subject analysis set title |
Did not maintain endoscopic response
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants who achieved endoscopic response at Week 6 and did not maintain endoscopic response at Week 16
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End point title |
Correlation of serum soluble human Suppression of Tumorigenicity 2 (ST2) levels with endoscopic activity of disease (assessed by endoscopy subscore of Mayo score) at Week 6 [1] | ||||||||
End point description |
ST2, a serum biomarker, was collected prior to study drug administration. 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. 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.
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End point type |
Primary
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End point timeframe |
Week 6
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical analyses were planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Correlation of serum soluble ST2 levels with histological activity (assessed by Geboes index) at Week 6 [2] | ||||||||
End point description |
ST2, a serum biomarker, was collected prior to study drug administration. 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. 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.
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End point type |
Primary
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End point timeframe |
Week 6
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical analyses were planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Correlation of serum soluble ST2 levels with endoscopic activity (assessed by endoscopy subscore of Mayo score) at Week 16 | ||||||||
End point description |
ST2, a serum biomarker, was collected prior to study drug administration. 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. 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.
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End point type |
Secondary
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End point timeframe |
Week 16
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| No statistical analyses for this end point | |||||||||
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End point title |
Correlation of serum soluble ST2 levels with histological activity (assessed by Geboes index) at Week 16 | ||||||||
End point description |
ST2, a serum biomarker, was collected prior to study drug administration. 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. 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.
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End point type |
Secondary
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End point timeframe |
Week 16
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| No statistical analyses for this end point | |||||||||
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End point title |
Correlation of serum soluble ST2 levels with faecal calprotectin levels at baseline and Week 6 and Week 16 | ||||||||||||||
End point description |
ST2 and faecal calprotectin, serum biomarkers, were collected prior to study drug administration. 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. 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).
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 6 and 16
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Correlation of serum soluble ST2 levels with clinical activity (assessed by total Mayo score) at Week 6 and Week 16 | ||||||||||||
End point description |
ST2, a serum biomarker, was collected prior to study drug administration. 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. 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.
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End point type |
Secondary
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End point timeframe |
Weeks 6 and 16
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline to Week 6 in ST2 levels in participants with Active versus Inactive UC | ||||||||||||||||||
End point description |
ST2, a serum biomarker, was collected prior to study drug administration. 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. 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.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 6
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
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) | ||||||||||||||||||
End point description |
ST2, a serum biomarker, was collected prior to study drug administration. 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. Analysis population includes all participants who had received study medication and achieved endoscopic response at Week 6.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 6
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Correlation of endoscopic Mayo subscore with Ulcerative Colitis Endoscopic Index Of Severity (UCEIS©) overall score at Week 6 and Week 16 | ||||||||||||
End point description |
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. 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.
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End point type |
Secondary
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End point timeframe |
Week 6 and Week 16
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 16 weeks
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Adverse event reporting additional description |
Analysis population includes all participants who received at least one dose of study medication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Golimumab treatment
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Reporting group description |
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. | ||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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11 Aug 2015 |
Amendment 1: major revisions to the protocol included the following:
• prolonging the screening period, to allow participants who are diagnosed during screening period with latent tuberculosis to receive treatment that is consistent with local guidelines before starting the study drug;
• updating the Tuberculosis assessment wording to clarify clinical situations that were not described in the original protocol;
• allow re-screening for participants in a very specific case, namely, participants who fail to meet the inclusion/exclusion criteria related with the severity of the disease. |
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18 Feb 2016 |
Amendment 2: major revisions to the protocol include the following • removal of the procedure “tuberculin skin test” due to its shortage in Portugal and after consultation with the regulatory authority; • inclusion of the procedure “evaluation of latent tuberculosis by specialized, trained, and licensed personnel”, at screening visit if not available within 2 months prior to study inclusion. |
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21 Apr 2017 |
Amendment 3: major revision to the protocol included the following:
• addition of the procedure “measurement of serum golimumab levels and anti-golimumab antibodies". |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
