Colitis, UlcerativePhase 4EVOLUTIONNCT02318667
Correlation of Soluble Suppression of Tumorigenicity 2 (ST2) With Golimumab (MK-8259) Response in Participants With Ulcerative Colitis (UC) (MK-8529-022).
A Phase 4 study testing Golimumab in people with Colitis, Ulcerative, run by Merck Sharp & Dohme LLC.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- Golimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- No sites listed yet
- Study dates
- 27 Feb 2015to 5 Sep 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- History of asthma
- History of autoimmune diseases
- History of hypertension
About this study
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.
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.
- Conditions
- Colitis, Ulcerative
- Being tested
- Golimumab
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GolimumabBiological
Also called SIMPONI
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.
| Study group | Role | What they receive |
|---|---|---|
| Golimumab treatment | Experimental | 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. Receives: Biological: Golimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Week 6
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 6 and Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2014 (estimated)
- Study start27 Feb 2015
- Primary completion21 Jun 2017
- Study completion5 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02318667
- Sponsor's protocol ID
- 8259-022
- Other IDs
- 2014-003262-25, MK-8259-022, 2014
- Acronym
- EVOLUTION
- Status last verified
- Jan 2021
- First submitted
- 12 Dec 2014
- Last updated
- 27 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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.
PubMed 30989180Magro 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. Ther Adv Gastroenterol. 2019 Aug 30;12:1756284819869141. doi: 10.1177/1756284819869141. eCollection 2019.
PubMed 31516554
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02318667
- Acronym / sponsor ID
- EVOLUTION / 8259-022
- Conditions
- Colitis, Ulcerative
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Feb 2015 (actual)
- Primary completion
- 21 Jun 2017 (actual)
- Study completion
- 5 Sep 2017 (actual)
- First posted
- 17 Dec 2014 (estimated)
- Results
- Posted 20 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Golimumab treatment | Experimental | Biological: GolimumabGolimumab 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (3 listed)
- History of asthma
- History of autoimmune diseases
- History of hypertension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GolimumabAlso: SIMPONIGolimumab 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. | Biological | Golimumab treatment |
Primary outcome
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.
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.
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.
8 secondary outcomes
Serum ST2 Level at Week 16
Time frame: Week 16
Correlation of Serum Soluble ST2 Levels With Endoscopic Activity (Assessed by Endoscopy Subscore of Mayo Score) at Week 16
Time frame: Week 16
Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 16
Time frame: Week 16
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
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
Change From Baseline to Week 6 in ST2 Levels in Participants With Active Versus Inactive UC
Time frame: 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)
Time frame: Baseline, Week 6
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30989180Magro 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.
- Results publication: PubMed 31516554Magro 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. Ther Adv Gastroenterol. 2019 Aug 30;12:1756284819869141. doi: 10.1177/1756284819869141. eCollection 2019.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Golimumab in people with Colitis, Ulcerative, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum ST2 Level at Week 6 (time frame: Week 6). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02318667, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2021.