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出境医 / 临床实验 / Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis (FAVOUR)

Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis (FAVOUR)

Study Description
Brief Summary:

The purpose of this study is to study the loss of vedolizumab in stool in patients with active ulcerative colitis (UC).

Patients with moderate-to-severe UC who are commencing induction therapy with vedolizumab will be enrolled into a prospective study and stool will be collected for faecal vedolizumab measurement at days 1, 4 and 7; and again at weeks 2, 6 and 14. They will also be evaluated at three time-points (weeks 2, 6 and 14) for clinical and biochemical UC disease activity as well as serum vedolizumab concentrations and anti-vedolizumab antibodies.


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

Detailed Description:

Primary objective

- To determine whether vedolizumab is present in significant quantities in the stool of patients receiving induction therapy with vedolizumab for active UC.

Secondary objective (s)

  • To evaluate whether the presence and quantity of vedolizumab in stool can be used to predict primary non-response to vedolizumab.
  • To explore whether a correlation exists between stool vedolizumab concentrations, serum vedolizumab concentrations and UC disease activity and extent.
  • To determine whether there is a correlation between stool and serum vedolizumab levels and trafficking of Th1/Th17 effector memory CD4+ T-cells (the key pathogenic subset in IBD) to the colon in UC.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis
Actual Study Start Date : July 1, 2019
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: Vedolizumab Biological: Vedolizumab
Intravenously administered selective leukocyte adhesion molecule inhibitor
Other Name: Entyvio
Outcome Measures
Primary Outcome Measures :
  1. Change in vedolizumab concentrations in stool [ Time Frame: Days 1, 4 and 7; and weeks 2, 6 and 14 ]
    Evaluated using an enzyme-linked immunosorbent assay (ELISA)


Secondary Outcome Measures :
  1. UC endoscopic activity [ Time Frame: Baseline and week 14 ]
    Evaluated using the Mayo Endoscopic Score: Mayo 0 = normal; Mayo 1= mild inflammation; Mayo 2 = moderate inflammation; Mayo 3 = severe inflammation

  2. UC endoscopic activity [ Time Frame: Baseline and week 14 ]
    Evaluated using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score: Vascular pattern= Normal (0), patchy loss (1), obliterated (2); Bleeding = None (0), mucosal (1), luminal mild (2), luminal moderate (3); Erosions/ulcers = None (0), erosions (1), superfical ulcer (2), deep ulcer (3)

  3. Clinical UC disease activity [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using Patient Reported Outcome 2 (PRO2) Questionnaire: Stool frequency= normal (0), 1-2 more (1), 3-4 more (2), 5 or more stools than normal (3); Rectal bleeding= no blood (0), streaks of blood <50% time (1), obvious blood >50% time (2), blood alone passes (3)

  4. Vedolizumab serum concentrations [ Time Frame: Weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)

  5. Vedolizumab anti-drug antibody levels [ Time Frame: Weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)

  6. Faecal calprotectin [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)

  7. Serum CRP (mg/L) [ Time Frame: Day 0, weeks 2, 6 and 14 ]
  8. Serum albumin (g/L) [40-52g/L] [ Time Frame: Day 0, weeks 2, 6 and 14 ]
  9. Quality of life questionnaire [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    IBD-Control questionnaire

  10. Clinical UC disease activity [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using the Simple Clinical Colitis Activity Index score: Bowel frequency day= 0-3 (0), 4-6 (1), 7-9 (2), >9 (3); Bowel frequency night= 0 (0), 1-3 (1), 4-6 (2); Urgency of defectation= None(0), Hurry (1), immediately (2), incontinence (3); Blood in stool = None (0), trace (1), occasional frank (2), usually frank (3); General well being= very well (0), slightly below par (1), poor (2), very poor (3), terrible (4); Extracolonic features (1 point for each) = arthritis, uveitis, erythema nodosum, pyoderma gangrenosum. Remission SCCAI ≤ 2; Response SCCAI ≤ 5, with a decrease by ≥ 2; Relapse SCCAI ≥ 5 (following a response)

  11. UC histological activity [ Time Frame: Day 0 and week 14 ]
    Evaluated using Nancy Histological Index


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

Inclusion Criteria:

  • Aged 18 years or over, either male or female

  • Moderate-to-severe UC, defined as:

    - SCCAI > 5 and, i. A raised fecal calprotectin (> 59 μg/g) or, ii. A raised CRP (> 5 mg/L) or, iii. Endoscopic disease activity Mayo 2 or above, Evaluated within 6 weeks of study enrollment

  • Commencing vedolizumab treatment
  • Sufficient English language skills to understand the patient information sheet and consent form

Exclusion Criteria:

  • Contra-indication to vedolizumab (i.e. known serious or severe hypersensitivity reaction to vedolizumab or any of its excipients)
  • Imminent need for colectomy (i.e. colectomy is being planned)
  • Previous ileoanal pouch formation
  • Active severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections
Contacts and Locations

Locations
Layout table for location information
United Kingdom
Guy's and St Thomas' NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Georgina Cunningham, MBBS    07378787000    georgina.cunningham@gstt.nhs.uk   
Contact: Peter Irving, MB BChir    02071882499    peter.irving@gstt.nhs.uk   
Sponsors and Collaborators
Guy's and St Thomas' NHS Foundation Trust
Takeda
Tracking Information
First Submitted Date  ICMJE February 13, 2019
First Posted Date  ICMJE July 2, 2019
Last Update Posted Date July 8, 2019
Actual Study Start Date  ICMJE July 1, 2019
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2019) 		Change in vedolizumab concentrations in stool [ Time Frame: Days 1, 4 and 7; and weeks 2, 6 and 14 ]
Evaluated using an enzyme-linked immunosorbent assay (ELISA)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2019)
  • UC endoscopic activity [ Time Frame: Baseline and week 14 ]
    Evaluated using the Mayo Endoscopic Score: Mayo 0 = normal; Mayo 1= mild inflammation; Mayo 2 = moderate inflammation; Mayo 3 = severe inflammation
  • UC endoscopic activity [ Time Frame: Baseline and week 14 ]
    Evaluated using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score: Vascular pattern= Normal (0), patchy loss (1), obliterated (2); Bleeding = None (0), mucosal (1), luminal mild (2), luminal moderate (3); Erosions/ulcers = None (0), erosions (1), superfical ulcer (2), deep ulcer (3)
  • Clinical UC disease activity [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using Patient Reported Outcome 2 (PRO2) Questionnaire: Stool frequency= normal (0), 1-2 more (1), 3-4 more (2), 5 or more stools than normal (3); Rectal bleeding= no blood (0), streaks of blood <50% time (1), obvious blood >50% time (2), blood alone passes (3)
  • Vedolizumab serum concentrations [ Time Frame: Weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
  • Vedolizumab anti-drug antibody levels [ Time Frame: Weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
  • Faecal calprotectin [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
  • Serum CRP (mg/L) [ Time Frame: Day 0, weeks 2, 6 and 14 ]
  • Serum albumin (g/L) [40-52g/L] [ Time Frame: Day 0, weeks 2, 6 and 14 ]
  • Quality of life questionnaire [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    IBD-Control questionnaire
  • Clinical UC disease activity [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using the Simple Clinical Colitis Activity Index score: Bowel frequency day= 0-3 (0), 4-6 (1), 7-9 (2), >9 (3); Bowel frequency night= 0 (0), 1-3 (1), 4-6 (2); Urgency of defectation= None(0), Hurry (1), immediately (2), incontinence (3); Blood in stool = None (0), trace (1), occasional frank (2), usually frank (3); General well being= very well (0), slightly below par (1), poor (2), very poor (3), terrible (4); Extracolonic features (1 point for each) = arthritis, uveitis, erythema nodosum, pyoderma gangrenosum. Remission SCCAI ≤ 2; Response SCCAI ≤ 5, with a decrease by ≥ 2; Relapse SCCAI ≥ 5 (following a response)
  • UC histological activity [ Time Frame: Day 0 and week 14 ]
    Evaluated using Nancy Histological Index
Original Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2019)
  • UC endoscopic activity [ Time Frame: Baseline and week 14 ]
    Evaluated using the Mayo Endoscopic Score: Mayo 0 = normal; Mayo 1= mild inflammation; Mayo 2 = moderate inflammation; Mayo 3 = severe inflammation
  • UC endoscopic activity [ Time Frame: Baseline and week 14 ]
    Evaluated using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score: Vascular pattern= Normal (0), patchy loss (1), obliterated (2); Bleeding = None (0), mucosal (1), luminal mild (2), luminal moderate (3); Erosions/ulcers = None (0), erosions (1), superfical ulcer (2), deep ulcer (3)
  • Clinical UC disease activity [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using Patient Reported Outcome 2 (PRO2) Questionnaire
  • Vedolizumab serum concentrations [ Time Frame: Weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
  • Vedolizumab anti-drug antibody levels [ Time Frame: Weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
  • Faecal calprotectin [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
  • Serum CRP (mg/L) [ Time Frame: Day 0, weeks 2, 6 and 14 ]
  • Serum albumin (g/L) [ Time Frame: Day 0, weeks 2, 6 and 14 ]
  • Quality of life questionnaire [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    IBD-Control questionnaire
  • Clinical UC disease activity [ Time Frame: Day 0, weeks 2, 6 and 14 ]
    Evaluated using the Simple Clinical Colitis Activity Index score: Remission SCCAI ≤ 2; Response SCCAI ≤ 5, with a decrease by ≥ 2; Relapse SCCAI ≥ 5 (following a response)
  • UC histological activity [ Time Frame: Day 0 and week 14 ]
    Evaluated using Nancy Histological Index
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis
Official Title  ICMJE Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis
Brief Summary

The purpose of this study is to study the loss of vedolizumab in stool in patients with active ulcerative colitis (UC).

Patients with moderate-to-severe UC who are commencing induction therapy with vedolizumab will be enrolled into a prospective study and stool will be collected for faecal vedolizumab measurement at days 1, 4 and 7; and again at weeks 2, 6 and 14. They will also be evaluated at three time-points (weeks 2, 6 and 14) for clinical and biochemical UC disease activity as well as serum vedolizumab concentrations and anti-vedolizumab antibodies.
Detailed Description

Primary objective

- To determine whether vedolizumab is present in significant quantities in the stool of patients receiving induction therapy with vedolizumab for active UC.

Secondary objective (s)

  • To evaluate whether the presence and quantity of vedolizumab in stool can be used to predict primary non-response to vedolizumab.
  • To explore whether a correlation exists between stool vedolizumab concentrations, serum vedolizumab concentrations and UC disease activity and extent.
  • To determine whether there is a correlation between stool and serum vedolizumab levels and trafficking of Th1/Th17 effector memory CD4+ T-cells (the key pathogenic subset in IBD) to the colon in UC.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE Biological: Vedolizumab
Intravenously administered selective leukocyte adhesion molecule inhibitor
Other Name: Entyvio
Study Arms  ICMJE Experimental: Vedolizumab
Intervention: Biological: Vedolizumab
Publications *
  • D'Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, Lémann M, Marteau P, Rutgeerts P, Schölmerich J, Sutherland LR. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007 Feb;132(2):763-86. Epub 2006 Dec 20. Review.
  • Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987 Dec 24;317(26):1625-9.
  • Travis SP, Schnell D, Krzeski P, Abreu MT, Altman DG, Colombel JF, Feagan BG, Hanauer SB, Lichtenstein GR, Marteau PR, Reinisch W, Sands BE, Yacyshyn BR, Schnell P, Bernhardt CA, Mary JY, Sandborn WJ. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology. 2013 Nov;145(5):987-95. doi: 10.1053/j.gastro.2013.07.024. Epub 2013 Jul 25.
  • Jairath V, Khanna R, Zou GY, Stitt L, Mosli M, Vandervoort MK, D'Haens G, Sandborn WJ, Feagan BG, Levesque BG. Development of interim patient-reported outcome measures for the assessment of ulcerative colitis disease activity in clinical trials. Aliment Pharmacol Ther. 2015 Nov;42(10):1200-10. doi: 10.1111/apt.13408. Epub 2015 Sep 21.
  • Travis SP, Schnell D, Krzeski P, Abreu MT, Altman DG, Colombel JF, Feagan BG, Hanauer SB, Lémann M, Lichtenstein GR, Marteau PR, Reinisch W, Sands BE, Yacyshyn BR, Bernhardt CA, Mary JY, Sandborn WJ. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012 Apr;61(4):535-42. doi: 10.1136/gutjnl-2011-300486. Epub 2011 Oct 13.
  • Bodger K, Ormerod C, Shackcloth D, Harrison M; IBD Control Collaborative. Development and validation of a rapid, generic measure of disease control from the patient's perspective: the IBD-control questionnaire. Gut. 2014 Jul;63(7):1092-102. doi: 10.1136/gutjnl-2013-305600. Epub 2013 Oct 9.
  • Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, Bastien C, Cahn V, Cadiot G, Diebold MD, Danese S, Reinisch W, Schreiber S, Travis S, Peyrin-Biroulet L. Development and validation of the Nancy histological index for UC. Gut. 2017 Jan;66(1):43-49. doi: 10.1136/gutjnl-2015-310187. Epub 2015 Oct 13.
  • Globig AM, Hennecke N, Martin B, Seidl M, Ruf G, Hasselblatt P, Thimme R, Bengsch B. Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-γ+IL-17+coproducing CD4+ T cells in active inflammatory bowel disease. Inflamm Bowel Dis. 2014 Dec;20(12):2321-9. doi: 10.1097/MIB.0000000000000210.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 1, 2019) 		30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged 18 years or over, either male or female

  • Moderate-to-severe UC, defined as:

    - SCCAI > 5 and, i. A raised fecal calprotectin (> 59 μg/g) or, ii. A raised CRP (> 5 mg/L) or, iii. Endoscopic disease activity Mayo 2 or above, Evaluated within 6 weeks of study enrollment

  • Commencing vedolizumab treatment
  • Sufficient English language skills to understand the patient information sheet and consent form

Exclusion Criteria:

  • Contra-indication to vedolizumab (i.e. known serious or severe hypersensitivity reaction to vedolizumab or any of its excipients)
  • Imminent need for colectomy (i.e. colectomy is being planned)
  • Previous ileoanal pouch formation
  • Active severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04006080
Other Study ID Numbers  ICMJE 2018-002794-21
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Guy's and St Thomas' NHS Foundation Trust
Study Sponsor  ICMJE Guy's and St Thomas' NHS Foundation Trust
Collaborators  ICMJE Takeda
Investigators  ICMJE Not Provided
PRS Account Guy's and St Thomas' NHS Foundation Trust
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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