Effects of Mongersen (GED-0301) on Endoscopic and Clinical Outcomes in Patients With Active Crohn's Disease

被引：60

作者：

Feagan, Brian G. ^{[1
,2
]}

Sands, Bruce E. ^{[3
]}

Rossiter, Guillermo ^{[4
]}

Li, Xiaobin ^{[4
]}

Usiskin, Keith ^{[4
]}

Zhan, Xiaojiang ^{[4
]}

Colombel, Jean-Frederic ^{[3
]}

机构：

[1] Roberts Clin Trials, London, ON, Canada

[2] Western Univ, London, ON, Canada

[3] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[4] Celgene Corp, Summit, NJ USA

来源：

GASTROENTEROLOGY | 2018年 / 154卷 / 01期

关键词：

CDAI; Clinical Efficacy; IBD; Randomized; INFLAMMATORY BOWEL DISEASES; ANTISENSE OLIGONUCLEOTIDE; INDUCTION THERAPY; DOUBLE-BLIND; SMAD7; TRIAL; INHIBITOR; PHASE-2; TARGET;

D O I：

10.1053/j.gastro.2017.08.035

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

GED-0301 is an antisense oligodeoxynucleotide with a sequence complementary to the Smad7 mRNA transcript. Smad7 is a negative regulator of transforming growth factor-beta, which is increased in the intestinal mucosa of patients with active Crohn's disease (CD). We randomly assigned 63 CD patients to 4-, 8-, or 12-week treatment groups receiving oral GED-0301 (160 mg/day). The primary objective was to determine GED-0301's effect on endoscopic CD measures; secondary objectives included effects on clinical activity. Endoscopic improvement was observed in 37% of participants with evaluable endoscopy results at week 12. At week 12, 32% (4 weeks), 35% (8 weeks), and 48% (12 weeks) of patients receiving GED-0301 were in remission (CD activity index score <150); corresponding reductions from baseline in mean CD activity index scores were -124, -112, and -133 points. No new safety signals were observed. These findings support a GED-0301 benefit in active CD.

引用

页码：61 / +

页数：10

共 14 条

[1] Management Strategies to Improve Outcomes of Patients With Inflammatory Bowel Diseases [J].

Colombel, Jean-Frederic ;

Narula, Neeraj ;

Peyrin-Biroulet, Laurent .

GASTROENTEROLOGY, 2017, 152 (02) :351-+

[2] Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study [J].

Feagan, Brian G. ;

Sandborn, William J. ;

D'Haens, Geert ;

Panes, Julian ;

Kaser, Arthur ;

Ferrante, Marc ;

Louis, Edouard ;

Franchimont, Denis ;

Dewit, Olivier ;

Seidler, Ursula ;

Kim, Kyung-Jo ;

Neurath, Markus F. ;

Schreiber, Stefan ;

Scholl, Paul ;

Pamulapati, Chandrasena ;

Lalovic, Bojan ;

Visvanathan, Sudha ;

Padula, Steven J. ;

Herichova, Ivona ;

Soaita, Adina ;

Hall, David B. ;

Bocher, Wulf O. .

LANCET, 2017, 389 (10080) :1699-1709

[3] Validation of Endoscopic Activity Scores in Patients With Crohn's Disease Based on a Post Hoc Analysis of Data From SONIC [J].

Ferrante, Marc ;

Colombel, Jean-Frederic ;

Sandborn, William J. ;

Reinisch, Walter ;

Mantzaris, Gerassimos J. ;

Kornbluth, Asher ;

Rachmilewitz, Daniel ;

Lichtiger, Simon ;

D'Haens, Geert R. ;

Van Der Woude, Christien J. ;

Danese, Silvio ;

Diamond, Robert H. ;

Oortwijn, Alessandra Faria ;

Tang, Kezhen L. ;

Miller, Michael ;

Cornillie, Freddy ;

Rutgeerts, Paul J. .

GASTROENTEROLOGY, 2013, 145 (05) :978-+

[4] Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial [J].

Hanauer, SB ;

Sandborn, WJ ;

Rutgeerts, P ;

Fedorak, RN ;

Lukas, M ;

Macintosh, D ;

Panaccione, R ;

Wolf, D ;

Pollack, P .

GASTROENTEROLOGY, 2006, 130 (02) :323-332

[5] Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease [J].

Jairath, V. ;

Zou, G. ;

Parker, C. E. ;

MacDonald, J. K. ;

Mosli, M. H. ;

AlAmeel, T. ;

Al Beshir, M. ;

AlMadi, M. ;

Al-Taweel, T. ;

Atkinson, N. S. S. ;

Biswas, S. ;

Chapman, T. P. ;

Dulai, P. S. ;

Glaire, M. A. ;

Hoekman, D. ;

Kherad, O. ;

Koutsoumpas, A. ;

Minas, E. ;

Restellini, S. ;

Samaan, M. A. ;

Khanna, R. ;

Levesque, B. G. ;

D'Haens, G. ;

Sandborn, W. J. ;

Feagan, B. G. .

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2017, 45 (08) :1021-1042

[6] Smad7 and its Potential as Therapeutic Target in Inflammatory Bowel Diseases [J].

Laudisi, Federica ;

Dinallo, Vincenzo ;

Di Fusco, Davide ;

Monteleone, Giovanni .

CURRENT DRUG METABOLISM, 2016, 17 (03) :303-306

[7] Post-transcriptional regulation of Smad7 in the gut of patients with inflammatory bowel disease [J].

Monteleone, G ;

Blanco, GD ;

Monteleone, I ;

Fina, D ;

Caruso, R ;

Gioia, V ;

Ballerini, S ;

Federici, G ;

Bernardini, S ;

Pallone, F ;

MacDonald, TT .

GASTROENTEROLOGY, 2005, 129 (05) :1420-1429

[8] Mongersen, an Oral SMAD7 Antisense Oligonucleotide, and Crohn's Disease [J].

Monteleone, Giovanni ;

Neurath, Markus F. ;

Ardizzone, Sandro ;

Di Sabatino, Antonio ;

Fantini, Massimo C. ;

Castiglione, Fabiana ;

Scribano, Maria L. ;

Armuzzi, Alessandro ;

Caprioli, Flavio ;

Sturniolo, Giacomo C. ;

Rogai, Francesca ;

Vecchi, Maurizio ;

Atreya, Raja ;

Bossa, Fabrizio ;

Onali, Sara ;

Fichera, Maria ;

Corazza, Gino R. ;

Biancone, Livia ;

Savarino, Vincenzo ;

Pica, Roberta ;

Orlando, Ambrogio ;

Pallone, Francesco .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (12) :1104-1113

[9] Phase I Clinical Trial of Smad7 Knockdown Using Antisense Oligonucleotide in Patients With Active Crohn's Disease [J].

Monteleone, Giovanni ;

Fantini, Massimo C. ;

Onali, Sara ;

Zorzi, Francesca ;

Sancesario, Giulia ;

Bernardini, Sergio ;

Calabrese, Emma ;

Viti, Francesca ;

Monteleone, Ivan ;

Biancone, Livia ;

Pallone, Francesco .

MOLECULAR THERAPY, 2012, 20 (04) :870-876

[10] Mucosal healing in inflammatory bowel diseases: a systematic review [J].

Neurath, Markus F. ;

Travis, Simon P. L. .

GUT, 2012, 61 (11) :1619-1635

← 1 2 →