What question did this study set out to answer?

This trial aims to evaluate the safety and effectiveness of intravenous vedolizumab for treating moderate-to-severe ulcerative colitis in pediatric patients.

January 23, 2026

DOP037Efficacy and safety of intravenous vedolizumab in paediatric patients with moderate-to-severe Ulcerative Colitis: Results from the KEPLER phase 3 trial

Key Points

This trial aims to evaluate the safety and effectiveness of intravenous vedolizumab for treating moderate-to-severe ulcerative colitis in pediatric patients.
Phase 3, single-arm clinical trial
Enrolled 121 pediatric patients aged 2-17 with moderate-to-severe ulcerative colitis
Administered vedolizumab intravenous induction therapy followed by maintenance therapy
Evaluated clinical remission and adverse events over 54 weeks
47.3% of patients achieved clinical remission at Week 54
34.7% achieved clinical remission at Week 14
29.0% had sustained clinical remission at Week 54
5.8% of patients developed anti-vedolizumab antibodies
85.8% experienced treatment-emergent adverse events, with 5.3% being serious

Abstract

Abstract Background Approved treatment options for children and adolescents with ulcerative colitis (UC) are limited. 1 The KEPLER phase 3 trial evaluated the efficacy, immunogenicity, pharmacokinetics (PK) and safety of vedolizumab (VDZ), an anti-α4β7 integrin biologic, administered as intravenous (IV) induction and maintenance therapy in children and adolescents with moderately to severely active UC. Methods This phase 3, single arm trial (NCT04779307) enrolled patients with moderate-to-severe UC (modified Mayo score of 5-9 with endoscopic subscore ≥2) aged 2-17 years and weighing ≥10kg with prior failure of conventional therapy such as steroids, immunomodulators, and/or tumour necrosis factor (TNF) antagonists. VDZ IV was administered during a 14-week, open-label induction period followed by a 40-week, randomised, double-blind maintenance period evaluating low- (LD) or high-dose (HD) VDZ (1: 1) by body weight (10-15kg 100 vs 150mg; 15-30kg 100 vs 200mg; ≥30kg 150 vs 300mg) given every 8 weeks. The primary endpoint was clinical remission by modified Mayo score at Week 54 in the intention-to-treat maintenance population. Secondary endpoints included clinical remission at Week 14, sustained clinical remission (at Weeks 14 and 54), corticosteroid-free clinical remission at Week 54, immunogenicity, PK, and safety. Results The trial enrolled 121 patients (10-15kg, n = 3; 15-30kg, n = 27; ≥30kg, n = 91), of whom 120 were dosed; 93 were subsequently randomised into LD (n = 47) or HD n = 46) groups for maintenance therapy (Table 1). Forty-four of 93 (47. 3%) patients achieved the primary endpoint of clinical remission at Week 54, with similar proportions in LD and HD groups (Fig. 1A). Clinical remission rates at Week 54 for patients categorised by weight, age, anti-TNF exposure, and baseline corticosteroid use are shown in Fig. 1B-E. Forty-two of 121 (34. 7%) patients achieved clinical remission at Week 14. At Week 54, 27/93 (29. 0%) patients achieved sustained clinical remission. Anti-VDZ antibodies occurred in 7/120 (5. 8%) VDZ-exposed patients, including neutralizing antibodies in 4 (3. 3%) ; similar VDZ serum trough levels were observed across weight groups. In the safety population, 103/120 (85. 8%) patients had treatment emergent adverse events (TEAEs), including 15/120 (12. 5%) related to VDZ. Twenty-five of 468 (5. 3%) TEAEs were serious. Five (4. 2%) patients had serious VDZ-related TEAEs. Seven (5. 8%) patients had TEAEs leading to VDZ discontinuation (most common: UC worsening, n = 3; infection, n = 3). Conclusion LD and HD VDZ IV were effective for children and adolescents with UC, including those with prior anti-TNF or corticosteroid failure. Similar rates were observed in adult patients with UC. 2 VDZ was well tolerated, with no new safety signals identified. References: 1. Vuijk SA et al. J Crohns Colitis. 2024;18 (Supplement₂): ii31-ii45. 2. Feagan BG et al. N Engl J Med. 2013;369 (8): 699-710. Conflict of interest: Turner, Dan: DT has received consultation fees, research grants, royalties or honorarium from Janssen, Pfizer, Shaare Zedek Medical Center, Hospital for Sick Children, Ferring, AbbVie, Takeda, Prometheus Biosciences, Eli Lilly, Sorriso Pharmaceuticals, Boehringer Ingelheim, Galapagos, BMS, Alfasigma and Merck. Kierkuś, Jarosław: JK has received grant or other support from Abbvie, Nestle, and Nutricia. Korczowski, Bartosz: BK has received grant support from Johnson & Johnson and Takeda. Strisciuglio, Caterina: CS has received consultation fees from Aboca and Sonofi. CS has acted as a Principle Investigator for Astrazeneca, Novalac, and Takeda. Chen, Jie: No conflict of interest Takaki, Yugo: No conflict of interest Szakos, Erzsébet: ES has acted as a Principle Investigator for Abbvie, Janssen, Pfizer, and Takeda. Arumugam, Ramalingam: No conflict of interest Rizvi, Anita: Employee of the study sponsor, Takeda, and holds Takeda stock or stock options. Yoon, MinJung: Employee of the study sponsor, Takeda, and holds Takeda stock or stock options. Campagne, Olivia: Employee of the study sponsor, Takeda, and holds Takeda stock or stock options. Angellotti, Edith: Employee of the study sponsor, Takeda, and holds Takeda stock or stock options. Candela, Ninfa: Employee of the study sponsor, Takeda, and holds Takeda stock or stock options. Velazco, Nerissa: I am a full-time employee of Takeda Pharmaceutical Company Limited. I have no additional financial interests, advisory roles, or external relationships that would influence my objectivity in relation to this work beyond my employment with Takeda.

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