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Background and Aims Report results from VISIBLE 2, a randomised, double-blind, placebo-controlled phase 3 trial evaluating a new subcutaneous [SC] vedolizumab formulation as maintenance treatment in adults with moderately to severely active Crohn’s disease [CD]. Methods Following open-label vedolizumab 300 mg intravenous induction therapy at Weeks 0 and 2, Week 6 clinical responders (≥70-point decrease in CD Activity Index [CDAI] score from baseline) were randomised 2:1 to receive double-blind maintenance vedolizumab 108 mg SC or placebo every 2 weeks until Week 50. Assessments at Week 52 included clinical remission [primary endpoint; CDAI≤150], enhanced clinical response [≥100-point decrease in CDAI from baseline], corticosteroid-free clinical remission among patients using a corticosteroid at baseline, clinical remission in anti-tumour necrosis factor [anti-TNF]-naïve patients, and safety. Results Following vedolizumab intravenous induction, 275 patients were randomised to vedolizumab SC and 135 to placebo maintenance. At Week 52, 48.0% of patients receiving vedolizumab SC versus 34.3% receiving placebo were in clinical remission [p=0.008]. Enhanced clinical response at Week 52 was achieved by 52.0% versus 44.8% of patients receiving vedolizumab SC versus placebo, respectively [p=0.167]. At Week 52, 45.3% and 18.2% of patients receiving vedolizumab SC and placebo, respectively, were in corticosteroid-free clinical remission, and 48.6% of anti-TNF-naïve patients receiving vedolizumab SC and 42.9% receiving placebo were in clinical remission. Injection site reaction was the only new safety finding observed for vedolizumab SC [2.9%]. Conclusions Vedolizumab SC is an effective and safe maintenance therapy in patients with CD who responded to two infusions of vedolizumab intravenous induction therapy.

Funding information Takeda Pharmaceutical Company[Correction added on 2 July 2021, after first online publication: the ClinicalTrials.gov number in the Methods-Study subject section has been corrected from "NCT02802735" to "NCT02892409" in this current version.] Aims: Helicobacter pylori (Hp) eradication plays a key role in the treatment and prevention of peptic ulcer diseases. Increasing clarithromycin resistance in Hp necessitates more effective treatments for eradication, such as bismuth-containing quadruple therapy. We aimed to compare the safety and pharmacokinetics (PK) of bismuth between vonoprazan-and lansoprazole-containing quadruple therapy in Hppositive subjects.Methods: In this randomised, double-blind, parallel-group study, Hp-positive subjects were randomised to receive vonoprazan-or lansoprazole-containing quadruple therapy. Each subject received vonoprazan 20 mg or lansoprazole 30 mg combined with bismuth 220 mg, clarithromycin 500 mg and amoxicillin 1000 mg twice daily for 14 days. Blood sampling and urine collection for bismuth PK were conducted predose and up to 12 hours postdose at steady-state. The PK parameters of bismuth were derived using a noncompartmental method and compared between treatments.An exploratory breath test for Hp was conducted at screening and at the follow-up visit on day 42. Safety was assessed by adverse event monitoring, physical examinations, vital signs, 12-lead electrocardiograms and clinical laboratory tests.Results: A total of 30 subjects were randomised and 26 subjects completed the study (12 in the vonoprazan group and 14 in the lansoprazole group). The systemic exposure of bismuth in the 2 treatments was comparable (5% difference). All subjects turned negative for Hp at the follow-up visit. No significant difference in safety profiles was noted between the 2 treatments. Conclusion:The systemic exposure of bismuth was similar between vonoprazan-and lansoprazole-containing quadruple therapy. Vonoprazan-containing quadruple therapy was safe and well tolerated.

Background and Aims To date, there are no systematic pharmacokinetic [PK] data on vedolizumab in paediatric inflammatory bowel disease [IBD]. We report results from HUBBLE, a dose-ranging, phase 2 trial evaluating the PK, safety, and efficacy of intravenous vedolizumab for paediatric IBD. Methods Enrolled patients [aged 2‒17 years] with moderate to severe ulcerative colitis [UC] or Crohn’s disease [CD] and body weight ≥10 kg were randomised by weight to receive low- or high-dose vedolizumab [≥30 kg, 150 or 300 mg; <30 kg, 100 or 200 mg] on Day 1 and Weeks 2, 6, and 14. Week 14 assessments included PK, clinical response, and exposure-response relationship. Safety and immunogenicity were assessed. Results Randomised patients weighing ≥30 kg [UC, n=25; CD, n=24] and <30 kg [UC, n=19; CD, n=21] had baseline mean [standard deviation] age of 13.5 [2.5] and 7.6 [3.2] years, respectively. In almost all indication and weight groups, area under concentration curve and average concentration increased approximately 2-fold from low to high dose; trough concentration was higher in each high-dose arm compared with the low-dose arms. At Week 14, clinical response occurred in 40.0‒69.2% of patients with UC and 33.3‒63.6% with CD in both weight groups. Clinical responders with UC generally had higher trough concentration versus non-responders, while this trend was not observed in CD. Fourteen percent [12/88] of patients had treatment-related adverse events and 6.8% [6/88] had anti-drug antibodies. Conclusions Vedolizumab exposure increased in an approximate dose-proportional manner. No clear dose-response relationship was observed in this limited cohort. No new safety signals were identified.

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