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| Name | Class |
|---|---|
| Adknoma Health Research | INDUSTRY |
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The primary endpoint will be evaluated through the following variables: PUCAI score, IFX levels, and steroid treatment.
Clinical response to IFX will be evaluated through the PUCAI score. The response will be considered clinically significant if PUCAI points continue maintained below 30 during the study period. The IFX response will also be determined by IFX serum levels. A therapeutic IFX level, i.e. for achieving an adequate clinical response, is established above 6 μg/mL. Finally, the necessity, or not, of a steroid treatment during the study period will also be indicative of successful efficacy with GMA.
The trial has the following objectives:
Primary objective (PO):
The primary endpoint will be evaluated through the following variables: PUCAI score, IFX levels, and steroid treatment.
Clinical response to IFX will be evaluated through the PUCAI score. The response will be considered clinically significant if PUCAI points continue maintained below 30 during the study period. The IFX response will also be determined by IFX serum levels. A therapeutic IFX level, i.e. for achieving an adequate clinical response, is established above 6 μg/mL. Finally, the necessity, or not, of a steroid treatment during the study period will also be indicative of successful efficacy with GMA.
Secondary objectives (SO):
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adacolumn | Experimental | Adacolumn is a non-pharmacological treatment which reduces the inflammation by removing specifically targeted white blood cells from the blood circulation. The Adacolumn is designed to be used in combination with the Adamonitor and its Adastand, and the Adacircuit. The column has a capacity of 335 mL and is filled with cellulose acetate beads of 2 mm in diameter as the column adsorptive leukocytapheresis carriers. The carriers are bathed in 130 mL of sterile saline until use when the column is primed with additional sterile saline and then with heparinized saline prior to use. Patients will receive 10 sessions with Adacolumn. It would be reduced between 5 - 10, according to the patient´s response and following PI valuation. Patients will receive Adacolumn with IFX for that period of time. Patients will have received previously IFX for 12-16 weeks. visits will be conducted every week, for the application of Adacolumn. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adacolumn | Device | The study will consist of 10 sessions of Adacolumn® treatment (once per week) and a follow-up period (from week 12 to week 40 since study inclusion). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Primary objective:evaluate if Adacolumn® can sustain clinical response to IFX for 12 weeks of follow-up (V.11) or 40 weeks of follow-up (V18). Clinical response to IFX will be evaluated through PUCAI SCORE | Description of PUCAI score as continuous variable at V.11 and at V.18 will be performed. Response to IFX will be clinically significant if PUCAI score continues maintained below 30 during the study (follow-up visits), so the nº and % of patients with a PUCAI score below 30 points in all visits between baseline to V.11 and baseline to V.18 will be described. Furthermore, comparison scores in both visits (baseline vs. V.11 and baseline vs. V.18) will be performed, by means of absolute and relative changes | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| Primary objective: evaluate if Adacolumn® can sustain clinical response to IFX for 12 weeks of follow-up (V.11) or 40 weeks of follow-up (V18). Clinical response to IFX will be evaluated through IFX-LEVELS | Description of IFX levels as continuous variable at V.11 and at V.18 will be performed. Response to IFX will be clinically significant if IFX levels > 6 μg/mL during the study, so the nº and % of patients with a IFX level > 6 μg/mL in all visits between baseline to V.11 and baseline to V.18 will be described. Furthermore, comparison between IFX levels in both visits will be performed, by means of absolute and relative changes | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| Primary objective:evaluate if Adacolumn® can sustain clinical response to IFX for 12 weeks of follow-up (V.11) or 40 weeks of follow-up (V18). Clinical response to IFX will be evaluated through STEROIDS USE | Description of the number and percentage of patients with a change in steroids treatment from baseline to V.11 and from baseline to V.18. Furthermore, comparison between visits will be performed. | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| Measure | Description | Time Frame |
|---|---|---|
| To evaluate the IFX and ATI level variations in the treatment regimen during the study period. Quantification of IFX trough and ATI levels, and description of the IFX dose at baseline, 12 and 40 weeks of follow-up | Description of IFX blood and ATI levels as continuous variables at baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Their variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change. Moreover, description of IFX dose by kilogram will be described in these visits |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pablo Zapico | Contact | 34 687 975 712 | p.zapico@adacyte.com |
| Name | Affiliation | Role |
|---|---|---|
| Francisco Javier MartÃn de Carpi | Hospital San Joan de Deu | Study Chair |
| Jorge Manuel Bastos Amil Dias | CHU Sao Joao | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Coimbra | Recruiting | Coimbra | Portugal |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12921115 | Background | Saniabadi AR, Hanai H, Takeuchi K, Umemura K, Nakashima M, Adachi T, Shima C, Bjarnason I, Lofberg R. Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial. 2003 Feb;7(1):48-59. doi: 10.1046/j.1526-0968.2003.00012.x. | |
| 11309823 |
| Label | URL |
|---|---|
| Adacyte Therapeutics Therapeutics. Adacolumn®. Instructions for use | View source |
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| Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| To measure the PUCAI score variation during the study period. Measurement of PUCAI score at baseline, 12 and 40 weeks of follow-up. | Description of PUCAI score as continuous variable at baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Its variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| To determine the percentage of patients maintaining steroid-free response during the study period at 12 and 40 weeks. | Description of the number and percentage of patients changing the behaviour of steroids treatment (use or not use) from baseline visit to Visit 11 (12 weeks) and from baseline visit to Visit 18 (40 weeks) will be computed. Furthermore, comparison between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be performed | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| To describe the number of flare-ups during the study period. Patients experiencing flares-ups during the study period. | Description of the number of patients experienced flare-ups and the accumulate number of flare-ups from baseline visit to Visit 11 and from baseline visit to Visit 18 will be computed. | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| To measure faecal calprotectin level during the study period. Quantification of faecal calprotectin level at baseline, 12 and 40 weeks of follow-up. Faecal calprotectin is associated with clinical remission with levels higher than 150 μg/g. | Description of faecal calprotectin level as continuous variable at baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Their variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change. As levels of faecal calprotectin > 150 μg/g are associated with clinical remission, the number and percentage of patients with faecal calprotectin > 150 μg/g will be described. Furthermore, comparison between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be performed. | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| To monitor the evolution of biochemical markers of inflammatory activity in UC and other laboratory parameters. Measurement of C-reactive protein, ESR, haemoglobin, albumin, platelet levels, PT, granulocytes at baseline, 12(V11) and 40 weeks(V18) | Description of CRP, ESR, haemoglobin, albumin platelet levels, PT and granulocytes as continuous variables at baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Their variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change. | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| To determine the evolution of leucocyte counts in peripheral blood during the study period. Quantification of leucocyte counts in peripheral blood at baseline, 12 and 40 weeks of follow-up. | Description of leucocyte counts as continuous variable at Baseline visit, Visit 11 (12 weeks) and Visit 18 (40 weeks) will be performed. Its variation between visits (baseline vs. Visit 11 and baseline vs. Visit 18) will be analysed by means of absolute and relative change | Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| To evaluate the safety of Adacolumn® during the study period, all the recorded AEs will be described by: |
| Baseline visit vs Visit 11 (12 weeks) (interim analysis). Baseline visit vs Visit 18 (40 weeks) (for final analysis) |
| Hospital Santa Maria | Recruiting | Lisbon | Portugal |
|
| Hospital Soa Joao | Recruiting | Porto | Portugal |
|
| Hospital H. Sant Joan de Déu | Recruiting | Sant Joan Despà | Barcelona | Spain |
|
| Hospital Universitari Vall d'Hebron | Recruiting | Barcelona | Spain |
|
| Hospital Infantil Universitario Niño Jesús | Recruiting | Madrid | Spain |
|
| Hospital Materno-Infantil del H.U.R. de Málaga | Recruiting | Málaga | Spain |
|
| Hospital U. Ntra Señora de Candelaria | Recruiting | Santa Cruz de Tenerife | Spain |
|
| Complejo H. Regional Virgen Del RocÃo | Recruiting | Seville | Spain |
|
| Hospital Universitari I Politècnic La Fe | Recruiting | Valencia | Spain |
|
| Shimoyama T, Sawada K, Hiwatashi N, Sawada T, Matsueda K, Munakata A, Asakura H, Tanaka T, Kasukawa R, Kimura K, Suzuki Y, Nagamachi Y, Muto T, Nagawa H, Iizuka B, Baba S, Nasu M, Kataoka T, Kashiwagi N, Saniabadi AR. Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher. 2001;16(1):1-9. doi: 10.1002/jca.1000. |
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| 15185858 | Background | Suzuki Y, Yoshimura N, Saniabadi AR, Saito Y. Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid naive patients with active ulcerative colitis: a prospective uncontrolled study. Dig Dis Sci. 2004 Apr;49(4):565-71. doi: 10.1023/b:ddas.0000026299.43792.ae. |
| 17004123 | Background | Suzuki Y, Yoshimura N, Fukuda K, Shirai K, Saito Y, Saniabadi AR. A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis. Dig Dis Sci. 2006 Nov;51(11):2031-8. doi: 10.1007/s10620-006-9199-9. Epub 2006 Sep 27. |
| 15017514 | Background | Hanai H, Watanabe F, Takeuchi K, Iida T, Yamada M, Iwaoka Y, Saniabadi A, Matsushita I, Sato Y, Tozawa K, Arai H, Furuta T, Sugimoto K, Bjarnason I. Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective, uncontrolled, pilot study. Clin Gastroenterol Hepatol. 2003 Jan;1(1):28-35. doi: 10.1053/jcgh.2003.50005. |
| 28432476 | Background | Saez-Gonzalez E, Moret I, Alvarez-Sotomayor D, Diaz-Jaime FC, Cerrillo E, Iborra M, Nos P, Beltran B. Immunological Mechanisms of Adsorptive Cytapheresis in Inflammatory Bowel Disease. Dig Dis Sci. 2017 Jun;62(6):1417-1425. doi: 10.1007/s10620-017-4577-z. Epub 2017 Apr 21. |
| 26818659 | Background | Dignass A, Akbar A, Hart A, Subramanian S, Bommelaer G, Baumgart DC, Grimaud JC, Cadiot G, Makins R, Hoque S, Bouguen G, Bonaz B. Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results. J Crohns Colitis. 2016 Jul;10(7):812-20. doi: 10.1093/ecco-jcc/jjw032. Epub 2016 Jan 27. |
| 29513111 | Background | Dignass A, Akbar A, Baumgart DC, Bommelaer G, Bouguen G, Cadiot G, Gillessen A, Grimaud JC, Hart A, Hoque S, Makins R, Michiels C, Moreau J, Premchand P, Ramlow W, Schanz S, Subramanian S, von Tirpitz C, Bonaz B. Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis. Scand J Gastroenterol. 2018 Apr;53(4):442-448. doi: 10.1080/00365521.2018.1447598. Epub 2018 Mar 7. |
| 18367949 | Background | Martin de Carpi J, Vilar P, Prieto G, Garcia Novo MD, Ribes C, Varea V. Safety and efficacy of granulocyte and monocyte adsorption apheresis in paediatric inflammatory bowel disease: a prospective pilot study. J Pediatr Gastroenterol Nutr. 2008 Apr;46(4):386-91. doi: 10.1097/MPG.0b013e31815604e5. |
| 27158208 | Background | Ruuska T, Kuster P, Grahnquist L, Lindgren F, Wewer AV. Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis. World J Gastroenterol. 2016 May 7;22(17):4389-96. doi: 10.3748/wjg.v22.i17.4389. |
| 28620414 | Background | Golbabapour S, da Silva LM, Athanasiou A. Immunological Aspects of Gastrointestinal Diseases. Gastroenterol Res Pract. 2017;2017:2891574. doi: 10.1155/2017/2891574. Epub 2017 May 17. No abstract available. |
| 10775225 | Background | Ghosh S, Shand A, Ferguson A. Ulcerative colitis. BMJ. 2000 Apr 22;320(7242):1119-23. doi: 10.1136/bmj.320.7242.1119. No abstract available. |
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| 24821616 | Background | Ruemmele FM, Hyams JS, Otley A, Griffiths A, Kolho KL, Dias JA, Levine A, Escher JC, Taminiau J, Veres G, Colombel JF, Vermeire S, Wilson DC, Turner D. Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee. Gut. 2015 Mar;64(3):438-46. doi: 10.1136/gutjnl-2014-307008. Epub 2014 May 12. |
| 28612637 | Background | Tanaka T, Yamamoto T, Sawada K, Sacco R. Treatment options for children and adolescents with inflammatory bowel disease: is granulomonocytapheresis an effective alternative to drug therapy? Expert Rev Gastroenterol Hepatol. 2017 Aug;11(8):749-758. doi: 10.1080/17474124.2017.1341309. Epub 2017 Jun 28. |
| 16339095 | Background | Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. |
| 26741065 | Background | Roda G, Jharap B, Neeraj N, Colombel JF. Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management. Clin Transl Gastroenterol. 2016 Jan 7;7(1):e135. doi: 10.1038/ctg.2015.63. |
| 25569737 | Background | Zitomersky NL, Atkinson BJ, Fournier K, Mitchell PD, Stern JB, Butler MC, Ashworth L, Hauenstein S, Heiner L, Chuang E, Singh S, Bousvaros A. Antibodies to infliximab are associated with lower infliximab levels and increased likelihood of surgery in pediatric IBD. Inflamm Bowel Dis. 2015 Feb;21(2):307-14. doi: 10.1097/MIB.0000000000000284. |
| 21050231 | Background | Thanaraj S, Hamlin PJ, Ford AC. Systematic review: granulocyte/monocyte adsorptive apheresis for ulcerative colitis. Aliment Pharmacol Ther. 2010 Dec;32(11-12):1297-306. doi: 10.1111/j.1365-2036.2010.04490.x. Epub 2010 Oct 14. |
| 28604509 | Background | Rolandsdotter H, Eberhardson M, Fagerberg UL, Finkel Y. Granulocyte and Monocyte Apheresis for Induction of Remission in Children With New-Onset Inflammatory Bowel Colitis. J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):84-89. doi: 10.1097/MPG.0000000000001641. |
| 22398094 | Background | Yamamoto T, Umegae S, Matsumoto K. Long-term clinical impact of early introduction of granulocyte and monocyte adsorptive apheresis in new onset, moderately active, extensive ulcerative colitis. J Crohns Colitis. 2012 Aug;6(7):750-5. doi: 10.1016/j.crohns.2011.12.009. Epub 2012 Jan 12. |
| 32166331 | Background | Yokoyama Y, Sawada K, Aoyama N, Yoshimura N, Sako M, Hirai F, Kashiwagi N, Suzuki Y. Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Patients With Inflammatory Bowel Disease Showing Lost Response to Infliximab. J Crohns Colitis. 2020 Sep 16;14(9):1264-1273. doi: 10.1093/ecco-jcc/jjaa051. |
| 30982369 | Background | Rodriguez-Lago I, Sempere L, Gutierrez A, Nunez A, Leo Carnerero E, Hinojosa E, Mora M, Canete F, Manosa M, Herrera C, Beltran B, Fores A, Arjona D, Barreiro-de Acosta M, Khorrami S, Aguirre U, Ginard D, Cabriada JL. Granulocyte-monocyte apheresis: an alternative combination therapy after loss of response to anti-TNF agents in ulcerative colitis. Scand J Gastroenterol. 2019 Apr;54(4):459-464. doi: 10.1080/00365521.2019.1600715. Epub 2019 Apr 14. |
| 29291447 | Background | Yokoyama Y, Kamikozuru K, Watanabe K, Nakamura S. Inflammatory bowel disease patients experiencing a loss of response to infliximab regain long-term response after undergoing granulocyte/monocyte apheresis: A case series. Cytokine. 2018 Mar;103:25-28. doi: 10.1016/j.cyto.2017.12.030. Epub 2017 Dec 29. |
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| 22485082 | Background | Measurement of infliximab and anti-infliximab antibody levels can help distinguish maintenance versus loss of response. Gastroenterol Hepatol (N Y). 2012 Feb;8(2):131-4. No abstract available. |
| 15710984 | Background | Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, Ricchiuti A, Marchi S, Bottai M. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut. 2005 Mar;54(3):364-8. doi: 10.1136/gut.2004.043406. |
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| 30044357 | Background | Turner D, Ruemmele FM, Orlanski-Meyer E, Griffiths AM, de Carpi JM, Bronsky J, Veres G, Aloi M, Strisciuglio C, Braegger CP, Assa A, Romano C, Hussey S, Stanton M, Pakarinen M, de Ridder L, Katsanos K, Croft N, Navas-Lopez V, Wilson DC, Lawrence S, Russell RK. Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018 Aug;67(2):257-291. doi: 10.1097/MPG.0000000000002035. |
| 21476027 | Background | Zhu M, Xu X, Nie F, Tong J, Xiao S, Ran Z. The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis. Int J Colorectal Dis. 2011 Aug;26(8):999-1007. doi: 10.1007/s00384-011-1193-9. Epub 2011 Apr 8. |
| Adacyte Therapeutics | View source |
| European Commission. Ethical Considerations for Clinical Trials | View source |
| European Medicines Agency. Informed Consent for Paediatric Clinical Trials in Europe 2015 | View source |
| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D015212 | Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
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