Phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study of ustekinumab in patients with Takayasu arteritis.

Objectives: Takayasu arteritis (TAK) is a rare, chronic large vessel vasculitis with unmet treatment needs. This phase 3 study aimed to evaluate efficacy, safety, pharmacokinetics and immunogenicity of ustekinumab (UST) in Japanese patients with TAK. Methods: Patients with TAK who had relapsed ≤12 weeks prior to study intervention administration and achieved remission thereafter with standard-of-care including corticosteroid intensification were randomized 1:1 to receive UST or matching placebo with protocol-defined oral glucocorticoid taper regimen. The double-blind (DB) phase was up to the patient's relapse/total of 35 relapse events, followed by the open-label extension (OLE) phase. Primary endpoint was the time to relapse of TAK per protocol-defined criteria through the end of the DB phase. Results: The study was terminated early due to patient recruitment challenge. Of 14 patients randomized, 8 relapsed during the DB phase (UST: 4/6; placebo: 4/8). The median time to relapse (weeks) was 11.14 (95% CI: 4.14, not estimated [NE]) for UST and 12.64 (95% confidence interval [CI]: 12.14, NE) for placebo (hazard ratio [HR] = 1.86 [95% CI: 0.41, 8.47]). In the DB phase, one patient in each group reported serious adverse event (SAE; UST: vascular pseudoaneurysm and brachiocephalic artery stenosis; placebo: cholecystitis); none were related to study intervention. Through the OLE phase, 1/4 (25.0%) patients in the UST-UST group (vascular graft infection considered related to study intervention) and none in the placebo-UST had SAEs. There were no serious infections/deaths throughout the study. Conclusion: The efficacy of UST in patients with TAK cannot be adequately assessed as the pre-determined sample size was not reached, and the study was prematurely terminated. No new safety signal of UST was identified. Trial registration: Clinicaltrials.gov, https://clinicaltrials.gov, NCT04882072; jrct.niph.go.jp, https://jrct.niph.go.jp, jRCT2061210007; Clinical Registry, CR108981.