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Phase I clinical trial of Smad7 knockdown using antisense oligonucleotide in patients with active Crohn's disease

Giovanni Monteleone1, Massimo C Fantini, Sara Onali

  • 1Dipartimento di Medicina Interna, Università Tor Vergata, Rome, Italy. Gi.Monteleone@Med.uniroma2.it

Molecular Therapy : the Journal of the American Society of Gene Therapy
|January 19, 2012
PubMed

Insights

GED0301, an Smad7 antisense oligonucleotide, is safe and well-tolerated in Crohn's disease patients. This study shows promising results for this novel therapeutic approach in managing inflammatory signals in CD.

Area of Science:

  • Gastroenterology
  • Immunology
  • Pharmacology

Background:

  • High Smad7 levels in Crohn's disease (CD) gut inhibit transforming growth factor-β1 (TGF-β1) immunosuppression, exacerbating inflammation.
  • Smad7 knockdown using GED0301 has shown efficacy in experimental colitis models in mice.

Purpose of the Study:

  • To assess the safety and tolerability of GED0301 in patients with active, steroid-dependent/resistant CD.
  • To evaluate dose-escalation effects of oral GED0301.

Main Methods:

  • Phase 1, open-label, dose-escalation clinical study.
  • 15 patients with active CD received oral GED0301 (40, 80, or 160 mg) once daily for 7 days.
  • Safety, tolerability, and changes in inflammatory cytokine-expressing CCR9-positive T cells were monitored.

Main Results:

  • No serious adverse events were reported, and GED0301 was well tolerated.
  • All patients completed the study; most adverse events were mild and unrelated to treatment.
  • GED0301 treatment led to a reduction in inflammatory cytokine-expressing CCR9-positive T cells in blood.

Conclusions:

  • GED0301 is safe and well-tolerated in patients with active CD.
  • This study provides the first clinical evidence of GED0301's safety profile in this patient population.
  • Further investigation into GED0301's therapeutic potential for Crohn's disease is warranted.

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