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A Phase 1, Multiple-Dose Study of Vedolizumab in Japanese Patients With Ulcerative Colitis.

ABSTRACT: Although previous studies have shown that patients with ulcerative colitis may benefit from treatment with vedolizumab, a humanized monoclonal antibody targeting the ?₄ ?₇ integrin heterodimer, no data exist in Japanese populations. The aim of this phase 1, open-label, multicenter study was to assess the pharmacokinetics, pharmacodynamics, efficacy, and safety of vedolizumab in Japanese patients with ulcerative colitis. Adult patients with confirmed ulcerative colitis received either 150 mg (step 1) or 300 mg (step 2) of intravenous (IV) vedolizumab on days 1, 15, and 43 of the study protocol. Pharmacokinetic, pharmacodynamic, safety, and efficacy parameters were all assessed through study end (day 239). Nine patients were enrolled in this study (150 mg, n = 3; 300 mg, n = 6). Patients who received vedolizumab IV 300 mg had approximately twice the drug exposure of those receiving vedolizumab IV 150 mg (day 1 AUC_day14 744 vs 408 ?g·d/mL) and a longer-lasting maximal saturation of ?₄ ?₇ integrin (155 vs 99 days). The number of treatment-emergent adverse events, all of which were mild or moderate in intensity, was similar between the 150-mg (15 events) and 300-mg (20 events) groups. The 2 patients (150 mg group) not in clinical remission by partial Mayo score at the start of the study met the criteria for clinical remission on days 15 and 155 of the study, respectively. In conclusion, in Japanese patients with ulcerative colitis, vedolizumab showed similar pharmacokinetic and pharmacodynamic results to those seen in non-Japanese patients. Vedolizumab was well tolerated and demonstrated clinical activity consistent with previous studies.

SUBMITTER: Kobayashi K

PROVIDER: S-EPMC6718004 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A Phase 1, Multiple-Dose Study of Vedolizumab in Japanese Patients With Ulcerative Colitis.

Kobayashi Kiyonori K Suzuki Yasuo Y Watanabe Kenji K Oda Kazunori K Mukae Miyuki M Yamada Akihiro A Yamagami Hirokazu H Nishimura Akira A Okamoto Hiroyuki H

Journal of clinical pharmacology 20180907 2

Although previous studies have shown that patients with ulcerative colitis may benefit from treatment with vedolizumab, a humanized monoclonal antibody targeting the α<sub>4</sub> β<sub>7</sub> integrin heterodimer, no data exist in Japanese populations. The aim of this phase 1, open-label, multicenter study was to assess the pharmacokinetics, pharmacodynamics, efficacy, and safety of vedolizumab in Japanese patients with ulcerative colitis. Adult patients with confirmed ulcerative colitis recei ...[more]

PMID: 30192378

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Project description:BackgroundVedolizumab safety and efficacy have been established in many populations all over the world, but have never been studied in Japan. We report results from a Phase 3, randomized, double-blind, placebo-controlled study of vedolizumab in Japanese patients with active ulcerative colitis (UC).MethodsPatients with moderate-to-severe UC were enrolled into Cohort 1 (double-blinded) or Cohort 2 (open-label) in the induction phase. Cohort 1 was randomized 2:1 to receive 300 mg vedolizumab or placebo, while Cohort 2 received vedolizumab 300 mg only, at Weeks 0, 2, and 6. Patients from Cohorts 1 and 2 showing a clinical response to vedolizumab at Week 10 were randomized 1:1 to receive vedolizumab or placebo (double-blinded) at Week 14 and then every 8 weeks up to Week 54 as the maintenance phase. The primary endpoint was clinical response at Week 10, for the induction phase, and clinical remission at Week 60, for the maintenance phase.ResultsA total of 292 patients were enrolled into the induction phase (246 in Cohort 1, 46 in Cohort 2); 83 patients achieved response to vedolizumab and were subsequently enrolled into the maintenance phase. Clinical response rates at Week 10 were 39.6% (65/164) and 32.9% (27/82) in the vedolizumab and placebo groups in Cohort 1, respectively (adjusted odds ratio [AOR] = 1.37, 95% CI 0.779-2.399; p = 0.2722). In the maintenance phase, clinical remission rate at Week 60 was significantly higher in the vedolizumab group, at 56.1% (23/41), versus 31.0% (13/42) for placebo (AOR = 2.88, 95% CI 1.168-7.108; p = 0.0210). Most adverse events were mild to moderate in intensity, and no deaths occurred during the study period.ConclusionsVedolizumab showed numerically greater efficacy compared with placebo as induction therapy, but the difference was not statistically significant. Vedolizumab was significantly superior to placebo as maintenance therapy in Japanese patients with UC. Vedolizumab has favourable safety and tolerability in these patients.Trial registrationClinicalTrials.gov: NCT02039505.

Dataset Information

A Phase 1, Multiple-Dose Study of Vedolizumab in Japanese Patients With Ulcerative Colitis.

Publications

A Phase 1, Multiple-Dose Study of Vedolizumab in Japanese Patients With Ulcerative Colitis.

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