Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis

Author:

Zhang Shenghong1,Chen Baili1,Wang Bangmao2,Chen Hong3,Li Yan4,Cao Qian5,Zhong Jie6,Shieh Ming-Jium7,Ran Zhihua8,Tang Tongyu9,Yang Ming10,Xu Beibei10,Wang Qiang10,Liu Yunjie10,Ma Lijia10,Wang Xiaolin11,Zhang Nan11,Zhang Su11,Guo Wenyu11,Huang Liang11,Schreiber Stefan12,Chen Minhu1

Affiliation:

1. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

2. Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China

3. Department of Gastroenterology, Affiliated ZhongDa Hospital, School of Medicine Southeast University, Nanjing, China

4. Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China

5. Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China

6. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

7. Department of Oncology, National Taiwan University Hospital & College of Medicine, Taipei, China

8. Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

9. Department of Gastroenterology, Bethune First Affiliated Hospital of Jilin University, Changchun, China

10. I-Mab Biopharma (Shanghai), Shanghai, China

11. I-Mab Biopharma (Hangzhou), Hangzhou, China

12. Department of Medicine I, University Hospital Schleswig Holstein, Kiel University, Kiel, Germany

Abstract

ImportanceOlamkicept, a soluble gp130-Fc-fusion-protein, selectively inhibits interleukin 6 (IL-6) trans-signaling by binding the soluble IL-6 receptor/IL-6 complex. It has anti-inflammatory activities in inflammatory murine models without immune suppression.ObjectiveTo assess the effect of olamkicept as induction therapy in patients with active ulcerative colitis.Design, Setting, and ParticipantsRandomized, double-blind, placebo-controlled phase 2 trial of olamkicept in 91 adults with active ulcerative colitis (full Mayo score ≥5, rectal bleeding score ≥1, endoscopy score ≥2) and an inadequate response to conventional therapy. The study was conducted at 22 clinical study sites in East Asia. Patients were recruited beginning in February 2018. Final follow-up occurred in December 2020.InterventionsEligible patients were randomized 1:1:1 to receive a biweekly intravenous infusion of olamkicept 600 mg (n = 30) or 300 mg (n = 31) or placebo (n = 30) for 12 weeks.Main Outcomes and MeasuresThe primary end point was clinical response at week 12 (defined as ≥3 and ≥30% decrease from baseline total Mayo score; range, 0-12 [worst] with ≥1 decrease and ≤1 in rectal bleeding [range, 0-3 {worst}]). There were 25 secondary efficacy outcomes, including clinical remission and mucosal healing at week 12.ResultsNinety-one patients (mean age, 41 years; 25 women [27.5%]) were randomized; 79 (86.8%) completed the trial. At week 12, more patients receiving olamkicept 600 mg (17/29 [58.6%]) or 300 mg (13/30 [43.3%]) achieved clinical response than placebo (10/29 [34.5%]), with adjusted difference vs placebo of 26.6% (90% CI, 6.2% to 47.1%; P = .03) for 600 mg and 8.3% (90% CI, −12.6% to 29.1%; P = .52) for 300 mg. Among patients randomized to receive 600 mg olamkicept, 16 of 25 secondary outcomes were statistically significant compared with placebo. Among patients randomized to receive 300 mg, 6 of 25 secondary outcomes were statistically significant compared with placebo. Treatment-related adverse events occurred in 53.3% (16/30) of patients receiving 600 mg olamkicept, 58.1% (18/31) receiving 300 mg olamkicept, and 50% (15/30) receiving placebo. The most common drug-related adverse events were bilirubin presence in the urine, hyperuricemia, and increased aspartate aminotransferase levels, and all were more common in the olamkicept groups compared with placebo.Conclusions and RelevanceAmong patients with active ulcerative colitis, biweekly infusion of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks compared with placebo. Further research is needed for replication and to assess longer-term efficacy and safety.Trial RegistrationClinicalTrials.gov Identifier: NCT03235752

Publisher

American Medical Association (AMA)

Subject

General Medicine

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