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Introduction <p>The monoclonal antibody ravagalimab is a potent antagonist to cluster of differentiation&#xa0;40 (CD40), which is elevated in inflammatory diseases such as ulcerative colitis (UC). This phase&#xa0;2a, open-label trial evaluated the efficacy and safety of ravagalimab as induction and maintenance treatment in patients with moderate-to-severe UC and who had inadequate response, loss of response, or intolerance to prior therapy.</p> Methods <p>Eligible adult patients with an adapted Mayo Score ≥ 5 points and an endoscopic subscore ≥ 2 received ravagalimab 600&#xa0;mg intravenously at baseline, then 300&#xa0;mg subcutaneously every 2&#xa0;weeks from weeks&#xa0;2 through 10. Patients with a clinical response at week&#xa0;12 continued into the maintenance period (ravagalimab 300&#xa0;mg subcutaneously every 2&#xa0;weeks through week&#xa0;102). The study was terminated early upon achieving the trial objectives at completion of the induction period.</p> Results <p>A total of 42 patients were enrolled and received at least one dose of ravagalimab. At baseline, over 80% of patients had severe endoscopic disease and failed/were intolerant to multiple prior biological/Janus kinase (JAK) therapies. Endoscopic improvement (Mayo endoscopic subscore of ≤ 1 without friability by independent central review) at week&#xa0;8, the primary efficacy endpoint, was achieved in 18% of ravagalimab-treated patients. Ravagalimab also led to clinical remission per adapted Mayo Score (stool frequency score ≤ 1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤ 1 without friability) and clinical response per adapted Mayo Score (a decrease of ≥ 30% and ≥ 2 points from baseline and a decrease in rectal bleeding score of ≥ 1 or an absolute rectal bleeding score of ≤ 1) at week&#xa0;8 in 9.5% and 40.2% of patients, respectively. In addition, gut biopsy analyses demonstrated target engagement, and pharmacodynamic modulation of a CD40-inducible gene (<i>ICAM1</i>) and CD40-dependent plasma cells. Ravagalimab was generally safe and well tolerated.</p> Conclusion <p>Ravagalimab treatment was efficacious and safe in patients with moderate-to-severe UC in this proof-of-concept study.</p> <p>Graphical Abstract available for this article.</p> Trial Registration <p>ClinicalTrials.gov identifier, NCT03695185.</p> Graphical Abstract <p></p>

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Efficacy and Safety of Ravagalimab in Patients with Moderate-to-Severe Ulcerative Colitis: Data from a Phase 2a Trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月1日

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  • Laurent Peyrin-Biroulet,
  • John Paul Seenan,
  • Alessandro Armuzzi,
  • Andreas Lazar,
  • Ann Eldred,
  • Thao Doan,
  • Sarah Blink Polakow,
  • Naim al Mahi,
  • Meng Liu,
  • Ahmed Nader,
  • Sumit Bhatnagar,
  • Stefan Schreiber

摘要

Introduction

The monoclonal antibody ravagalimab is a potent antagonist to cluster of differentiation 40 (CD40), which is elevated in inflammatory diseases such as ulcerative colitis (UC). This phase 2a, open-label trial evaluated the efficacy and safety of ravagalimab as induction and maintenance treatment in patients with moderate-to-severe UC and who had inadequate response, loss of response, or intolerance to prior therapy.

Methods

Eligible adult patients with an adapted Mayo Score ≥ 5 points and an endoscopic subscore ≥ 2 received ravagalimab 600 mg intravenously at baseline, then 300 mg subcutaneously every 2 weeks from weeks 2 through 10. Patients with a clinical response at week 12 continued into the maintenance period (ravagalimab 300 mg subcutaneously every 2 weeks through week 102). The study was terminated early upon achieving the trial objectives at completion of the induction period.

Results

A total of 42 patients were enrolled and received at least one dose of ravagalimab. At baseline, over 80% of patients had severe endoscopic disease and failed/were intolerant to multiple prior biological/Janus kinase (JAK) therapies. Endoscopic improvement (Mayo endoscopic subscore of ≤ 1 without friability by independent central review) at week 8, the primary efficacy endpoint, was achieved in 18% of ravagalimab-treated patients. Ravagalimab also led to clinical remission per adapted Mayo Score (stool frequency score ≤ 1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤ 1 without friability) and clinical response per adapted Mayo Score (a decrease of ≥ 30% and ≥ 2 points from baseline and a decrease in rectal bleeding score of ≥ 1 or an absolute rectal bleeding score of ≤ 1) at week 8 in 9.5% and 40.2% of patients, respectively. In addition, gut biopsy analyses demonstrated target engagement, and pharmacodynamic modulation of a CD40-inducible gene (ICAM1) and CD40-dependent plasma cells. Ravagalimab was generally safe and well tolerated.

Conclusion

Ravagalimab treatment was efficacious and safe in patients with moderate-to-severe UC in this proof-of-concept study.

Graphical Abstract available for this article.

Trial Registration

ClinicalTrials.gov identifier, NCT03695185.

Graphical Abstract