Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study

Abstract

Background: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF).

Methods: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20% reduction in parenteral support (PS) from baseline at week 24.

Results: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy.

Conclusion: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.

Keywords: gastroenterology; parenteral nutrition; pediatrics; short bowel syndrome.

© 2019 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.

Figures

Figure 1

Study design. After screening, site visits occurred at baseline (day 0) and at the indicated study weeks. For all other study weeks, patients were contacted by telephone. BL, baseline; SC, subcutaneous; SOC, standard of care.

Figure 2

CONSORT diagram. Patients in the teduglutide treatment arm received a once‐daily subcutaneous injection of 0.025 mg/kg or 0.05 mg/kg teduglutide.

Figure 3

Patients achieving the primary study efficacy/PD end point. Horizontal bars represent the difference in the percentage of patients achieving a ≥20% reduction in PS volume at week 24 for each teduglutide group and SOC group. PD, pharmacodynamics; PS, parenteral support; SOC, standard of care.

Figure 4

Percentage change from baseline in (A) PS volume and (B) PS calories per patient diary data and z‐score change from baseline in (C) body weight. Error bars represent the standard error. The week 24 vertical dotted line marks the end of the treatment period and the start of the follow‐up period. PS, parenteral support; SEM, standard error of the mean; SOC, standard of care.