Ustekinumab in Pediatric Patients with Moderately to Severely Active Crohn's Disease Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study.

ABSTRACT:

Background and aims

The objective was to evaluate the pharmacokinetics, safety/tolerability, and efficacy of ustekinumab in children with moderately to severely active Crohn's disease.

Methods

In this Phase 1, multicentre, 16-week, double-blind induction dose-ranging study (NCT02968108), patients aged 2-<18 years (body weight ≥10 kg) were randomized (1:1) to one of 2 weight range-based intravenous induction doses: 130mg vs 390mg in patients ≥40kg and 3mg/kg vs 9mg/kg in patients <40kg. At week 8, all patients received a single subcutaneous ustekinumab maintenance dose of 90mg in patients ≥40kg or 2mg/kg in patients <40kg.

Results

Forty-four patients were randomized and treated with ustekinumab (n=23 lower dose; n=21 higher dose); median (interquartile range) age was 13.0 (12-16) years. Pharmacokinetics were similar to those in adults with Crohn's disease. However, serum ustekinumab concentrations were lower among those with body weight <40kg compared with patients ≥40kg and the reference Phase 3 adult population. Through week 16, 73% of patients reported ≥1 adverse event (82.6% lower vs 62% higher dose); 2 discontinued due to adverse events (1 in each group). Serious adverse events occurred in 16% (26% lower, 5% higher dose), with Crohn's disease exacerbation being the most frequent. At week 16, 22%/29% (lower/higher dose) achieved clinical remission (Pediatric Crohn's Disease Activity Index ≤10).

Conclusions

The pharmacokinetics/safety profiles were generally consistent with those observed in adults with Crohn's disease. These results suggest a different dosing regimen may be required for patients <40kg than that employed in this study; additional pharmacokinetic analyses may be needed in this population.

SUBMITTER: Rosh JR 

PROVIDER: S-EPMC8575045 | biostudies-literature |

REPOSITORIES: biostudies-literature