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Golimumab Trough Levels in Patients With Ulcerative Colitis (GLMLEVEL)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03773445
Recruitment Status : Recruiting
First Posted : December 12, 2018
Last Update Posted : March 13, 2019
Sponsor:
Collaborators:
Hospital Universitario La Fe
Hospital Universitario 12 de Octubre
Hospital Universitario Ramon y Cajal
Gregorio Marañón Hospital
Complejo Hospitalario de Navarra
Hospital Universitario Fundación Alcorcón
Hospital Infanta Sofia
Hospital Clínico Universitario de Valencia
Puerta de Hierro University Hospital
Hospital Universitario La Paz
Hospital Universitario de Fuenlabrada
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Carlos Taxonera, Hospital San Carlos, Madrid

Brief Summary:
Proactive therapeutic drug monitoring of Anti-TNFs with drug titration to a therapeutic window is associated with favorable long-term therapeutic outcomes in IBD and may be superior to reactive therapeutic drug monitoring. Moreover, many exposure-response relationship studies have shown that higher serum anti-TNF drug concentrations are associated with better clinical outcomes in IBD, suggesting that it is maybe time to go from a 'treat-to-target' to a 'treat-to trough' therapeutic approach. In this scenario, there are very limited data regarding therapeutic drug monitoring with golimumab in UC and even no data regarding a therapeutic window to target for important objectives outcomes like mucosal healing and histological remission.

Condition or disease Intervention/treatment
Ulcerative Colitis Diagnostic Test: Golimumab trough levels Diagnostic Test: Antibodies to golimumab Diagnostic Test: Histology Diagnostic Test: Colonoscopy

Detailed Description:

Tumor necrosis factor (TNF)-α antagonists have changed the goals of ulcerative colitis (UC) treatment, with the focus now on preventing disease progression rather than just controlling symptoms. Anti-TNF agents have shown ability to achieve clinical remission and mucosal healing in UC. However, histological remission represents a target distinct from endoscopic healing in UC, and seems a better predictor of clinical outcomes. Moreover, histological remission and not mucosal healing has been associated with a reduced risk of colorectal cancer in UC. Infliximab was reported to induce histological remission in a significant proportion of UC patients. More recently, adalimumab was able to achieve histological remission in nearly one-third of anti-TNF naïve patients with moderately to severely active UC.

Reactive therapeutic drug monitoring of anti-TNF agents may help to identify mechanisms for loss of response and to guide selection of optimal intervention in individual patients and has been shown to be cost-effective compared with empiric dose escalation. Proactive therapeutic drug monitoring showed that anti-TNF trough levels are correlated with clinical response, clinical remission and mucosal healing in patients with inflammatory bowel disease (IBD). Conversely, inadequate serum drug concentrations and antidrug antibodies are associated with poor clinical outcomes. Recently, a study demonstrated that infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in patients with UC.

Golimumab, a subcutaneously administered fully human antibody to TNF, induces clinical response and remission in patients with moderately to severely active UC. In patients who responded to induction therapy, golimumab doses administered every 4 weeks as a maintenance regimen was effective in maintaining clinical response through 1 year. Available data on golimumab drug monitoring and exposure-response relationship in UC patients are from the PURSUIT trials. A positive association between golimumab levels and efficacy outcomes, including mucosal healing, was confirmed during both induction and maintenance portions of the PURSUIT studies.

Real life data regarding golimumab concentrations and clinical outcomes are lacking, with only a small observational study published. Besides, there are no data regarding the ability of golimumab to achieve histological remission in UC patients.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Association of Golimumab Trough Levels With Endoscopic and Histologic Healing in Patients With Ulcerative Colitis
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : November 30, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Golimumab


Intervention Details:
  • Diagnostic Test: Golimumab trough levels
    Golimumab trough levels taken immediately before the administration of the next subcutaneous dose of golimumab
  • Diagnostic Test: Antibodies to golimumab
    Antibodies to golimumab taken immediately before the administration of the next subcutaneous dose of golimumab
  • Diagnostic Test: Histology
    Histology of colonic biopsies using the Geboes Index
  • Diagnostic Test: Colonoscopy
    Colonoscopy to evaluate the endoscopic activity by a Mayo endoscopic subscore


Primary Outcome Measures :
  1. Correlation between Golimumab trough levels and Endoscopic remission [ Time Frame: Cross-Sectional: 15 days before or after the extraction of levels ]
    defined as a Mayo endoscopic subscore of 0

  2. Correlation between Golimumab trough levels and Endoscopic healing [ Time Frame: Cross-Sectional: 15 days before or after the extraction of levels ]
    defined as a Mayo endoscopic subscore of 0 or 1

  3. Correlation between Golimumab trough levels and Histological remission [ Time Frame: Cross-Sectional: 15 days before or after the extraction of levels ]
    defined as a Geboes index ≤3.0


Secondary Outcome Measures :
  1. Correlation between Golimumab trough levels and Clinical remission [ Time Frame: Cross-Sectional: 15 days before or after the extraction of levels ]
    defined as a total Mayo score ≤2 with no individual subscore exceeding 1 point

  2. Correlation between Golimumab trough levels and Clinical response [ Time Frame: Cross-Sectional: 15 days before or after the extraction of levels ]
    defined as a decrease from baseline in the total Mayo score of at least 3-points

  3. Receiver operating characteristic curve analysis [ Time Frame: Cross-Sectional: 15 days before or after the extraction of levels ]
    Thresholds of golimumab levels for outcomes 1 to 5 will be determined using the receiver operating characteristic curve analysis.

  4. C-reactive protein and fecal calprotectin. [ Time Frame: Cross-Sectional: 15 days before or after the extraction of levels ]
    Correlation between Golimumab trough levels with C-reactive protein and fecal calprotectin.

  5. Histological remission [ Time Frame: Cross-Sectional: 15 days before or after the extraction of levels ]
    Proportion of patients with Histological remission defined as a Geboes index ≤3.0


Biospecimen Retention:   Samples Without DNA
Serum and colonic biopsies


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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Eligible patients will include patients of at least 18 years old with moderate to severe UC treated with maintenance therapy with golimumab according to usual clinical practice and have received the induction regimen with the drug according to the EU label, followed by maintenance treatment for at least 6 months from the first dose of drug.

The study population will comprise all consecutive patients in which a programmed colonoscopy is indicated according to clinical practice for one of the following reasons:

  1. Based on a treat-to-target strategy
  2. Screening for prevention of colorectal cancer ( >8 years disease)
  3. In case of flare
  4. In case of long term remission
Criteria

Inclusion Criteria:

  • Age greater than or equal to 18 years.
  • Patients with a diagnosis of ulcerative colitis at least 12 months prior to the start of the study.
  • Patients previously treated with golimumab for ulcerative colitis prescribed according to the usual clinical practice of each center and who have received at least 5 maintenance doses according to the guidelines accepted in the technical file.
  • Sign of informed consent.

Exclusion Criteria:

  • Patients with Crohn's disease or colitis pending classification
  • Alterations in the coagulation that contraindicate the taking of biopsies
  • Patients with moderate-severe heart failure (grades III / IV NYHA)
  • Patients with tuberculosis or other serious infections such as septicemia, abscesses and opportunistic infections
  • Psychiatric illness that discourages participation in the study
  • Patients with a history of hypersensitivity to golimumab, to other murine proteins or to any of the excipients included in the golimumab data sheet
  • Withdrawal of the informed consent by the patient
  • Any other condition that in the opinion of the investigator discourages the participation of the subject in the study.

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): NCT03773445


Contacts
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Contact: Carlos Taxonera, Dr. 34-913303049 carlos.taxonera@salud.madrid.org
Contact: David Olivares, BD 34-913303713 david.olivares@salud.madrid.org

Locations
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Spain
Hospital Universitario Fundación Alcorcón Recruiting
Alcorcón, Madrid, Spain, 28922
Contact: Pilar López Serrano, Dr.       plopez@fhalcorcon.es   
Hospital Universitario Fuenlabrada Recruiting
Fuenlabrada, Madrid, Spain, 28942
Contact: Fernando Bermejo, Dr.       fernando.bermejo@salud.madrid.org   
Hospital Puerta de Hierro Recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Marta Calvo, Dr.       calvo.marta@gmail.com   
Hospital Infanta Sofia Recruiting
San Sebastián De Los Reyes, Madrid, Spain, 28703
Contact: Noemí Manceñido, Dr.       nmancenido@gmail.com   
Complejo Hospitalario de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Contact: Saioa Rubio, Dr.       saioa.rubio.iturria@cfnavarra.es   
Hospital Gregorio Marañón Recruiting
Madrid, Spain, 28007
Contact: Luis Alberto Menchén, Dr.       luisalberto.menchen@salud.madrid.org   
Hospital Universitario Ramon y Cajal Recruiting
Madrid, Spain, 28034
Contact: Francisco Mesonero, Dr.       pacomeso@hotmail.com   
Hospital Clinico San Carlos Recruiting
Madrid, Spain, 28040
Contact: Carlos Taxonera, Dr.    34-913303049    carlos.taxonera@salud.madrid.org   
Contact: David Olivares, BD    34-913303713    david.olivares@salud.madrid.org   
Hospital 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Begoña Casis, Dr.       bcasis63@gmail.com   
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: María Dolores Martín-Arranz, Dr.       mmartinarranz@gmail.com   
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Maia Boscá Watts, Dr.       maiabosca@yahoo.es   
Hospital Universitario La Fe Recruiting
Valencia, Spain, 46026
Contact: Marisa Iborra, Dr.       marisaiborra@hotmail.com   
Sponsors and Collaborators
Hospital San Carlos, Madrid
Hospital Universitario La Fe
Hospital Universitario 12 de Octubre
Hospital Universitario Ramon y Cajal
Gregorio Marañón Hospital
Complejo Hospitalario de Navarra
Hospital Universitario Fundación Alcorcón
Hospital Infanta Sofia
Hospital Clínico Universitario de Valencia
Puerta de Hierro University Hospital
Hospital Universitario La Paz
Hospital Universitario de Fuenlabrada
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Carlos Taxonera, Dr. Hospital San Carlos, Madrid
  Study Documents (Full-Text)

Documents provided by Carlos Taxonera, Hospital San Carlos, Madrid:
Study Protocol  [PDF] November 15, 2018
Informed Consent Form  [PDF] November 15, 2018

Publications of Results:

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Responsible Party: Carlos Taxonera, Dr., Hospital San Carlos, Madrid
ClinicalTrials.gov Identifier: NCT03773445    
Other Study ID Numbers: CTS-GOL-2018-01
First Posted: December 12, 2018    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Carlos Taxonera, Hospital San Carlos, Madrid:
ulcerative colitis
golimumab
simponi
therapeutic drug monitoring
endoscopic healing
histologic remission
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs