Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

Julián Panés; Damián García-Olmo; Gert Van Assche; Jean F. Colombel; Walter Reinisch; Daniel C. Baumgart; Axel Dignass; Maria Nachury; Marc Ferrante; Lili Kazemi-Shirazi; Jean C. Grimaud; Fernando de la Portilla; Eran Goldin; Marie Paule Richard; Mary Carmen Diez; Ignacio Tagarro; Anne Leselbaum; Silvio Danese; Julián Panés; Daniel C. Baumgart; Jean F. Colombel; Silvio Danese; Gert Van Assche; Walter Reinisch; Damián García-Olmo; Anton Stift; Jörg Tschmelitsch; Karl Mrak; Herbert Tilg; Irmgard Kroberger; André D'Hoore; Danny De Looze; Filip Baert; Paul Pattyn; Philippe Zerbib; Frank Zerbib; Stéphanie Viennot; Jean Louis Dupas; Pierre Charles Orsoni; Xavier Hebuterne; Amine Rahili; Matthieu Allez; Yves Panis; Max Reinshagen; Roland Scherer; Andreas Sturm; Wolfgang Kruis; Daniel Simon Duek; Matti Waterman; Bas Oldenburg

doi:10.1053/j.gastro.2017.12.020

Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

Julián Panés^*, Damián García-Olmo, Gert Van Assche, Jean F. Colombel, Walter Reinisch, Daniel C. Baumgart, Axel Dignass, Maria Nachury, Marc Ferrante, Lili Kazemi-Shirazi, Jean C. Grimaud, Fernando de la Portilla, Eran Goldin, Marie Paule Richard, Mary Carmen Diez, Ignacio Tagarro, Anne Leselbaum, Silvio Danese, Julián Panés, Daniel C. BaumgartJean F. Colombel, Silvio Danese, Gert Van Assche, Walter Reinisch, Damián García-Olmo, Anton Stift, Jörg Tschmelitsch, Karl Mrak, Herbert Tilg, Irmgard Kroberger, André D'Hoore, Danny De Looze, Filip Baert, Paul Pattyn, Philippe Zerbib, Frank Zerbib, Stéphanie Viennot, Jean Louis Dupas, Pierre Charles Orsoni, Xavier Hebuterne, Amine Rahili, Matthieu Allez, Yves Panis, Max Reinshagen, Roland Scherer, Andreas Sturm, Wolfgang Kruis, Daniel Simon Duek, Matti Waterman, Bas Oldenburg,

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5–31.2; P =.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2–31.2; P =.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1–31.1; P =.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. Conclusion: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.

Original language	English
Pages (from-to)	1334-1342.e4
Journal	Gastroenterology
Volume	154
Issue number	5
DOIs	https://doi.org/10.1053/j.gastro.2017.12.020
Publication status	Published - Apr 2018

Keywords

Anal Fistula
Cell Therapy
Clinical Remission
Combined Remission

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10.1053/j.gastro.2017.12.020

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Panés, J., García-Olmo, D., Van Assche, G., Colombel, J. F., Reinisch, W., Baumgart, D. C., Dignass, A., Nachury, M., Ferrante, M., Kazemi-Shirazi, L., Grimaud, J. C., de la Portilla, F., Goldin, E., Richard, M. P., Diez, M. C., Tagarro, I., Leselbaum, A., Danese, S., Panés, J. (2018). Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology, 154(5), 1334-1342.e4. https://doi.org/10.1053/j.gastro.2017.12.020

@article{aa75902edcdc41f5bc427a0458643a99,

title = "Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease",

abstract = "Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5–31.2; P =.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2–31.2; P =.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1–31.1; P =.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. Conclusion: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.",

keywords = "Anal Fistula, Cell Therapy, Clinical Remission, Combined Remission",

author = "Juli{\'a}n Pan{\'e}s and Dami{\'a}n Garc{\'i}a-Olmo and {Van Assche}, Gert and Colombel, {Jean F.} and Walter Reinisch and Baumgart, {Daniel C.} and Axel Dignass and Maria Nachury and Marc Ferrante and Lili Kazemi-Shirazi and Grimaud, {Jean C.} and {de la Portilla}, Fernando and Eran Goldin and Richard, {Marie Paule} and Diez, {Mary Carmen} and Ignacio Tagarro and Anne Leselbaum and Silvio Danese and Juli{\'a}n Pan{\'e}s and Baumgart, {Daniel C.} and Colombel, {Jean F.} and Silvio Danese and {Van Assche}, Gert and Walter Reinisch and Dami{\'a}n Garc{\'i}a-Olmo and Anton Stift and J{\"o}rg Tschmelitsch and Karl Mrak and Herbert Tilg and Irmgard Kroberger and Andr{\'e} D'Hoore and {De Looze}, Danny and Filip Baert and Paul Pattyn and Philippe Zerbib and Frank Zerbib and St{\'e}phanie Viennot and Dupas, {Jean Louis} and Orsoni, {Pierre Charles} and Xavier Hebuterne and Amine Rahili and Matthieu Allez and Yves Panis and Max Reinshagen and Roland Scherer and Andreas Sturm and Wolfgang Kruis and Duek, {Daniel Simon} and Matti Waterman and Bas Oldenburg",

note = "Funding Information: Funding This study was sponsored by TiGenix S.A.U. Writing assistance was provided by David Harrison (Cerebellum Communications Ltd.), who was funded by TiGenix S.A.U. Publisher Copyright: {\textcopyright} 2018 AGA Institute",

year = "2018",

month = apr,

doi = "10.1053/j.gastro.2017.12.020",

language = "English",

volume = "154",

pages = "1334--1342.e4",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders",

number = "5",

}

Panés, J, García-Olmo, D, Van Assche, G, Colombel, JF, Reinisch, W, Baumgart, DC, Dignass, A, Nachury, M, Ferrante, M, Kazemi-Shirazi, L, Grimaud, JC, de la Portilla, F, Goldin, E, Richard, MP, Diez, MC, Tagarro, I, Leselbaum, A, Danese, S, Panés, J, Baumgart, DC, Colombel, JF, Danese, S, Van Assche, G, Reinisch, W, García-Olmo, D, Stift, A, Tschmelitsch, J, Mrak, K, Tilg, H, Kroberger, I, D'Hoore, A, De Looze, D, Baert, F, Pattyn, P, Zerbib, P, Zerbib, F, Viennot, S, Dupas, JL, Orsoni, PC, Hebuterne, X, Rahili, A, Allez, M, Panis, Y, Reinshagen, M, Scherer, R, Sturm, A, Kruis, W, Duek, DS, Waterman, M, Oldenburg, B 2018, 'Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease', Gastroenterology, vol. 154, no. 5, pp. 1334-1342.e4. https://doi.org/10.1053/j.gastro.2017.12.020

TY - JOUR

T1 - Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

AU - Panés, Julián

AU - García-Olmo, Damián

AU - Van Assche, Gert

AU - Colombel, Jean F.

AU - Reinisch, Walter

AU - Baumgart, Daniel C.

AU - Dignass, Axel

AU - Nachury, Maria

AU - Ferrante, Marc

AU - Kazemi-Shirazi, Lili

AU - Grimaud, Jean C.

AU - de la Portilla, Fernando

AU - Goldin, Eran

AU - Richard, Marie Paule

AU - Diez, Mary Carmen

AU - Tagarro, Ignacio

AU - Leselbaum, Anne

AU - Danese, Silvio

AU - Panés, Julián

AU - Baumgart, Daniel C.

AU - Colombel, Jean F.

AU - Danese, Silvio

AU - Van Assche, Gert

AU - Reinisch, Walter

AU - García-Olmo, Damián

AU - Stift, Anton

AU - Tschmelitsch, Jörg

AU - Mrak, Karl

AU - Tilg, Herbert

AU - Kroberger, Irmgard

AU - D'Hoore, André

AU - De Looze, Danny

AU - Baert, Filip

AU - Pattyn, Paul

AU - Zerbib, Philippe

AU - Zerbib, Frank

AU - Viennot, Stéphanie

AU - Dupas, Jean Louis

AU - Orsoni, Pierre Charles

AU - Hebuterne, Xavier

AU - Rahili, Amine

AU - Allez, Matthieu

AU - Panis, Yves

AU - Reinshagen, Max

AU - Scherer, Roland

AU - Sturm, Andreas

AU - Kruis, Wolfgang

AU - Duek, Daniel Simon

AU - Waterman, Matti

AU - Oldenburg, Bas

N1 - Funding Information: Funding This study was sponsored by TiGenix S.A.U. Writing assistance was provided by David Harrison (Cerebellum Communications Ltd.), who was funded by TiGenix S.A.U. Publisher Copyright: © 2018 AGA Institute

PY - 2018/4

Y1 - 2018/4

N2 - Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5–31.2; P =.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2–31.2; P =.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1–31.1; P =.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. Conclusion: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.

AB - Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5–31.2; P =.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2–31.2; P =.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1–31.1; P =.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. Conclusion: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.

KW - Anal Fistula

KW - Cell Therapy

KW - Clinical Remission

KW - Combined Remission

UR - http://www.scopus.com/inward/record.url?scp=85043344645&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2017.12.020

DO - 10.1053/j.gastro.2017.12.020

M3 - Article

AN - SCOPUS:85043344645

SN - 0016-5085

VL - 154

SP - 1334-1342.e4

JO - Gastroenterology

JF - Gastroenterology

IS - 5

ER -

Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

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Keywords

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