This site is intended for healthcare professionals
Anti-integrins in IBD

Anti-integrin clinical trials

Read time: 25 mins
Last updated:18th May 2020

Anti-integrin clinical trials

Understand the story behind the development of new biological agents in ulcerative colitis and Crohn’s disease.

  • Explore the other emerging anti-integrin treatments that are currently being investigated in clinical trials.
  • See the efficacy and safety of vedolizumab in IBD, investigated in the GEMINI clinical trial programme.
  • Get an overview on the study results leading to market authorisation of vedolizumab.

Anti-integrins are changing the way inflammatory bowel disease is treated - a gut-selective treatment option may offer a promising choice.

Vedolizumab

The efficacy and safety of vedolizumab in IBD has been investigated in the GEMINI clinical trial programme. In this section you will find an overview on the study results leading to market authorisation of vedolizumab for the treatment of moderately to severely active ulcerative colitis, as well as detailed information on the trials. For more information on safety, click here.

For the GEMINI 1 trial, two integrated, randomised, double-blind, placebo-controlled trials investigated vedolizumab in patients with active ulcerative colitis. In the induction therapy phase, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at Week 6. In the maintenance therapy phase, patients in either cohort who had a response to vedolizumab at Week 6 were randomly assigned to continue receiving vedolizumab every 4 or 8 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0–12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1 (Feagan et al., 2013).

Register now for full access to medthority.com

Vedolizumab

The efficacy and safety of vedolizumab in inflammatory bowel disease (IBD) has been investigated in the GEMINI clinical trial programme. In this section you will find an overview on the study results leading to market authorisation of vedolizumab for the treatment of moderately to severely active Crohn’s disease (Entyvio® Summary of Product Characteristics. 2014), as well as detailed information on the trials. For more information on safety, click here.

In GEMINI 2, an integrated study with separate induction and maintenance trials, intravenous vedolizumab therapy (300 mg) was assessed in adult patients with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at Week 6. In the maintenance trial, 461 patients who had responded to vedolizumab were randomly assigned to receive placebo or vedolizumab every 4 or 8 weeks until Week 52 (Sandborn et al., 2013).

Register now for full access to medthority.com

References

Bellaguarda E, Keyashian K, Pekow J, Rubin DT, Cohen RD, Sakuraba A. Prevalence of antibodies against JC virus in patients with refractory Crohn’s disease and effects of natalizumab therapy. Clin Gastroenterol Hepatol. 2015;13:1919–25.

Berger JR, Aksamit AJ, Clifford DB, Davis L, Koralnik IJ, Sejvar JJ, et al. PML diagnostic criteria. Neurology. 2013;80:1430‒8.

Bozic C, Subramanyam M, Richman S, Plavina T, Zhang A, Ticho B. Anti-JC (JCV) antibody prevalence in the JCV epidemiology in MS (JEMS) trial. Eur J Neurol. 2014;21:229‒304.

Bravatà I, Alloca M, Fiorino G, Danese S. Integrins and adhesion molecules as targets to treat inflammatory bowel disease. Curr Opin Pharmacol. 2015;25:67–71.

Cimzia® Summary of Product Characteristics, 2014. Available at: https://www.medicines.org.uk/emc/product/7387/smpc (accessed October 2018).

Clinicaltrials.gov NCT00101946: Nine-weeks treatment with 683699 in subjects with moderately-to-severely active Crohn's disease. Available at: https://clinicaltrials.gov/ct2/show/NCT00101946 (accessed September 2018).

Clinicaltrials.gov NCT01164904. Safety, tolerability, pharmacokinetics and pharmacodynamics of AMG 181 in healthy subjects with mild to moderate ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT01164904 (accessed September 2018).

Clinicaltrials.gov NCT01276509. Study to test whether PF-00547659 is safe and improves disease symptoms in patients with Crohn’s disease (OPERA). Available at: https://clinicaltrials.gov/ct2/show/NCT01276509 (accessed September 2018).

Clinicaltrials.gov NCT01290042. Study to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of AMG 181. Available at: https://clinicaltrials.gov/ct2/show/NCT01290042 (accessed September 2018).

Clinicaltrials.gov NCT01298492. A study to monitor long-term treatment with PF-00547659 (OPERA II). Available at: https://clinicaltrials.gov/ct2/show/NCT01298492 (accessed September 2018).

Clinicaltrials.gov NCT01336465. Evaluate the efficacy and safety of rhuMAb beta7 in patients with moderate to severe ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT01336465 (accessed September 2018).

Clinicaltrials.gov NCT01345799. A study of TRK-170 for the treatment of Crohn’s disease. Available at: https://clinicaltrials.gov/ct2/show/NCT01345799 (accessed September 2018).

Clinicaltrials.gov NCT02100696. A study of the efficacy and safety of etrolizumab in ulcerative colitis participants who have previously been exposed to tumor necrosis factor (TNF) inhibitors. Available at: https://clinicaltrials.gov/ct2/show/NCT02100696 (accessed September 2018).

Clinicaltrials.gov NCT01771809. Study for participants with ulcerative colitis enrolled in etrolizumab Phase II/III studies. Available at: https://clinicaltrials.gov/ct2/show/NCT02118584 (accessed September 2018).

Clinicaltrials.gov NCT02136069. A study comparing the efficacy and safety of etrolizumab to infliximab in participants with moderate to severe ulcerative colitis who are naïve to tumor necrosis factor (TNF) inhibitors. Available at: https://clinicaltrials.gov/ct2/show/NCT02136069 (accessed September 2018).

Clinicaltrials.gov NCT02163759. A study comparing the efficacy and safety of etrolizumab with adalimumab and placebo in participants with moderate to severe ulcerative colitis (UC) in participants naïve to tumor necrosis factor (TNF) inhibitors (Study #1). Available at: https://clinicaltrials.gov/ct2/show/NCT02163759 (accessed September 2018).

Clinicaltrials.gov NCT02165215. A study of the efficacy and safety of etrolizumab treatment in the maintenance of disease remission in ulcerative colitis (UC) participants who are naïve to tumor necrosis factor (TNF) inhibitors. Available at: https://clinicaltrials.gov/ct2/show/NCT02165215 (accessed September 2018).

Clinicaltrials.gov NCT02171429. A study comparing the efficacy and safety of etrolizumab with adalimumab and placebo in participants with moderate to severe ulcerative colitis (UC) in participants naïve to tumor necrosis factor (TNF) inhibitors (Study #2). Available at: https://clinicaltrials.gov/ct2/show/NCT02171429 (accessed September 2018).

Clinicaltrials.gov NCT02394028. A study to assess whether etrolizumab is a safe and effective treatment for participants with moderately to severely active Crohn’s disease (CD). Available at: https://clinicaltrials.gov/ct2/show/NCT02394028 (accessed November 2018).

Clinicaltrials.gov NCT02403323. Open-label extension and safety study for patients with Crohn’s disease previously enrolled in the etrolizumab Phase III study GA29144. Available at: https://clinicaltrials.gov/ct2/show/NCT02403323 (accessed September 2018).

Clinicaltrials.gov NCT02895100. Safety and efficacy of PTG-100 in the treatment of moderate to severe ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT02895100 (accessed September 2018).

Clinicaltrials.gov NCT01696396. AMG 181 in subjects with moderate to severe Crohn’s disease. Available at: https://clinicaltrials.gov/ct2/show/NCT01696396 (accessed September 2018).

Clinicaltrials.gov NCT02118584. Study for participants with ulcerative colitis previously enrolled in etrolizumab Phase II/III studies. Available at: https://clinicaltrials.gov/ct2/show/NCT02118584 (accessed November 2018).

Clinicaltrials.gov NCT01620255. A study of PF-00547659 in patients with moderate to severe ulcerative colitis (TURANDOT). Available at: https://clinicaltrials.gov/ct2/show/NCT01620255 (accessed October 2018).

Clinicaltrials.gov NCT01694485. AMG 181 Phase 2 study in subjects with moderate to severe ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT01694485 (accessed October 2018).

Clinicaltrials.gov NCT02497469. An efficacy and safety study of vedolizumba intravenous (IV) compared to adalimumab subcutaneous (SC) in participants with ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT02497469 (accessed November 2018).

Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D’Haens G, et al. The safety of vedolizumab for ulcerative colitis and Crohn’s disease. Gut. 2017;66(5):839‒51.

Currò D, Pugliese D, Armuzzi A. Frontiers in drug research and development for inflammatory bowel disease. Front Pharmacol. 2017;8:400.

D’Haens GR, Reinisch W, Lee SD, Tarabar D, Louis E, Kłopocka M, et al. Long-term safety and efficacy of the anti-MAdCAM-1 monoclonal antibody SHP647 for the treatment of Crohn’s disease: the OPERA II study. Presented at the European Crohn’s and Colitis Organisation 2017, 15–18 February 2017. Barcelona, Spain. Oral presentation OP024.

Entyvio® Summary of Product Characteristics. 2014. Available at: https://www.medicines.org.uk/emc/product/5442 (accessed September 2018).

Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699–710.

Feagan BG, Rubin DT, Danese S, Vermeire S, Abhyankar B, Sankoh S, et al. Efficacy of vedolizumab induction and maintenance therapy in patients with ulcerative colitis, regardless of prior exposure to tumor necrosis factor antagonists. Clin Gastroenterol. 2017;15(2):229‒39.

Ferenczy MW, Marshall LJ, Nelson CD, Atwood WJ, Nath A, Khalili K, et al. Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev. 2012;25:471‒506.

Fiorino G, Gilardi D, Danese S. The clinical potential of etrolizumab in ulcerative colitis: hypes and hopes. Therap Adv Gastroenterol. 2016;9:503–12.

Guagnozzi D, Caprili R. Natalizumab in the treatment of Crohn’s disease. Biologics. 2008;2(2):275‒84.

Humira® Summary of Product Characteristics, 2008. Available at: https://www.medicines.org.uk/emc/product/9080/smpc (accessed October 2018).

Kleinschmidt-DeMasters and Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005;353(4):369‒74.

Lobatón T, Vermeire S, Van Assche G, Rutgeerts P. Review article: anti-adhesion therapies for inflammatory bowel disease. Ailment Pharmacol Ther. 2014;39(6):579‒94

Loftus EV Jr, Colombel JF, Feagan BG, Vermeire S, Sands BE, Danese S, et al. Long-term efficacy of vedolizumab for ulcerative colitis. J Crohns Colitis 2017a;11:400‒11.

Loftus EV, Colombel JF, Feagan B, Vermeire S, Sandborn W, Sands B, et al. Long-term effectiveness and safety of vedolizumab in patients with ulcerative colitis: 5-year cumulative exposure of GEMINI 1 completers rolling into the GEMINI open-label extension study. Presented at the European Crohn’s and Colitis Organisation 2017, 15–18 February 2017. Barcelona, Spain. 2017b. Poster presentation P209.

Mattheakis L, Fosser C, Saralaya R, Horsh K, Rao N, Bai L, et al. Model based predictions of the PTG-100 pharmacodynamic responses in ulcerative colitis patients. Presented at the 12th Congress of the European Crohn’s and Colitis Organisation 2017, 15–18 February 2017. Barcelona, Spain. Abstract P113.

Park SC, Jeen YT. Anti-integrin therapy for inflammatory bowel disease. World J Gastroenterol. 2018;24(17):1868–80.

Remicade® Summary of Product Characteristics, 2009. Available at: https://www.medicines.org.uk/emc/product/3831 (accessed October 2018).

Rosario M, Dirks NL, Milch C, Parikh A, Bargfrede M, Wyant T, et al. A review of the clinical pharmacokinetics, pharmacodynamics, and immunology of vedolizumab. Clin Pharmacokinet. 2007;56:1287‒301.

Rutgeerts P, Vermeire S, Van Assche G. Biological therapies for inflammatory bowel diseases. Gastroenterol. 2009;136(5):1182‒97.

Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369:711–21.

Sandborn WJ, Schreiber S, Tan MT, Tatro AR, Oh YS, Maciuca R. Etrolizumab demonstrated no difference among doses in symptomatic and endoscopic-based evaluation of remission in anti-TNF-α–naïve patients in a post-hoc analysis of the phase 2 ulcerative colitis trial (EUCALYPTUS). J Crohns Colitis 2017a;11:S278–9.

Sandborn WJ, Cyrille M, Berner Hansen M, Feagan BG, Loftus EV, Rogler G, et al. Efficacy and safety of abrilumab in subjects with moderate to severe ulcerative colitis: results of a phase 2B, randomized, double-blind, multiple-dose, placebo-controlled study. Gastroenterology. 2017b;152(5):S198.

Sandborn WJ, Cyrille M, Berner Hansen M, Feagan BG, Loftus Jr. EV, Vermeire S, et al. Efficacy and safety of abrilumab (AMG 181/MEDI 7183) therapy for moderate to severe Crohn’s disease. Presented at the European Crohn’s and Colitis Organisation 2017, 15–18 February 2017. Barcelona, Spain. 2017c. Oral presentation OP035.

Sandborn WJ, Baert F, Danese S, Krznarić Z, D’Haens G, Kobayashi T, et al. Efficacy and safety of a new vedolizumab subcutaneous formulation for ulcerative colitis: results of the VISABLE 1 Phase 3 trial. Presented at United European Gastroenterology (UEG) Week 2018, 20‒24th October, 2018. Vienna, Austria.  

Sands BE, Feagan BG, Rutgeerts P, Colombel JF, Sandborn WJ, Sy R, et al. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterol. 2014;147(3):618–27.e3.

Sands BE, Sandborn WJ, Van Assche G, Lukas M, Xu J, James A, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease in patients naïve to or who have failed Tumor Necrosis Factor antagonist therapy. Inflamm Bowel Dis. 2017;23(1):97‒106.

Schreiber S, Dignass A, Peyrin-Biroulet L, Hather G, Demuth D, Mosli M, et al. Systematic review with meta-analysis: real-world effectiveness and safety of vedolizumab in patients with inflammatory bowel disease. J Gastroenterol. 2018;53(9):1048–64.

Selinger C, Sandborn W, Panes J, Jones J, Hassanali A, Jocaob R, et al. OTU-003 Etrolizumab as induction therapy in moderate to severe Crohn’s disease: results from BERGAMOT cohort 1. Gut. 2018;67:A53.

Simponi® Summary of Product Characteristics, 2014. Available at: https://www.medicines.org.uk/emc/product/5133/smpc (accessed October 2018).

Soler J, Chapman T, Yang L, Wyant T, Egan R, Fedyk ER. The binding specificity and selective antagonism of vedolizumab, an anti-α4β7 integrin therapeutic antibody in development for inflammatory bowel disease. J Pharmacol Exp Ther. 2009;330(3):864‒75.

Stefanich EG, Danilenko DM, Wang H, O’Byrne S, Erikson R, Gelzleichhter T, et al. A humanized monoclonal antibody targeting the β7 integrin selectively blocks intestinal homing of T lymphocytes. Br J Pharmacol. 2011;162(8):1855‒70.

Stelara® Summary of Product Characteristics, 2013. Available at: https://www.medicines.org.uk/emc/product/4412/smpc (accessed October 2018).

Takazoe, M, Watanabe, M, Kawaguchi, T, Matsumoto, T, Oshitani, N, Hiwatashi, N, et al. S1066. Oral Alpha-4 Integrin Inhibitor (AJM300) in Patients with Active Crohn’s Disease - A Randomized, Double-Blind, Placebo-Controlled Trial. Gastroenterology. 2009;136(5):A–181.

Takeda. FDA approves Takeda's Entyvio (vedolizumab) for the treatment of adults with moderately to severely active ulcerative colitis or Crohn's disease [press release], Takeda 2014a. Available at: https://www.takeda.com/newsroom/newsreleases/2014/FDA-Approves-Takedas-Entyvio-vedolizumab-for-the-Treatment-of-Adults/ (accessed September 2018).

Takeda. Takeda receives European Commission marketing authorisation for Entyvio® (vedolizumab) for the treatment of ulcerative colitis and Crohn's disease, Takeda 2014b. Available at:  https://www.takeda.com/newsroom/newsreleases/2014/takeda-receives-european-commission-marketing-authorisation-for-entyvio-vedolizumab-for-the-treatment-of-ulcerative-colitis-and-crohns-disease/ (accessed August 2018).

Tysabri® Prescribing Information, 2017. Available at: https://www.tysabri.com/content/dam/commercial/multiple-sclerosis/tysabri/pat/en_us/pdfs/tysabri_prescribing_information.pdf (accessed September 2018).

U.S. Food and Drug Administration, 2008. BL 125104/33. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/125104s0033ltr.pdf (accessed August 2018).

U.S. Food and Drug Administration, 2004. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/125104s000_Natalizumab.cfm (accessed October 2018).

Vermeire S, O’Bryne S, Keir M, Williams M, Lu TT, Mansfield JC, et al. Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trials. Lancet. 2014;384:309–18.

Vermeire S, Loftus EV Jr, Colombel JF, Feagan BG, Sandborn WJ, Sands BE, et al. Long-term Efficacy of Vedolizumab for Crohn's Disease. J Crohn’s Colitis. 2017a;11(4):412–24.

Vermeire S, Sandborn W, Danese S, Hebuterne X, Salzberg B, Klopocka M, et al. Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017b;390(10090):135‒44.

Vermeire S, Loftus EV, Colombel JF, Feagan BG, Sandborn WJ, Sands BE, et al. Long-term effectiveness and safety of vedolizumab in patients with Crohn’s disease: 5-year cumulative exposure of GEMINI 2 completers rolling into the GEMINI open-label extension study. Presented at the 2017 Digestive Disease Week Annual Meeting. 6‒10th May, 2017c. Chicago. USA. Poster Su1931.

Wyant T, Leach T, Sankoh S, Wang Y, Paolino J, Pasetti MF, et al. Vedolizumab affects antibody responses to immunisation selectively in the gastrointestinal tract: randomised controlled trial results. Gut. 2015;64:77–83.

Wyant T, Fedyk E, Abhyankar B. An overview of the mechanism of action of the monoclonal antibody vedolizumab. J Crohn’s Colitis 2016;10(12):143–4.

Xeljanz® Summary of Product Characteristics, 2017. Available at: https://www.medicines.org.uk/emc/product/9410/smpc (accessed October 2018).

Zwicker S, Lira-Junior R, Höög C, Almer S, Boström EA. Systemic chemokine levels with “gut-specific” vedolizumab in patients with Inflammatory Bowel Disease—a pilot study. Int J Mol Sci. 2017;18(8):1827.

Developed by EPG Health for Medthority in collaboration with Takeda, with content provided by Takeda.