TY - JOUR
T1 - Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity
T2 - A multicenter, open-label, metabolic balance study
AU - Verbiest, Astrid
AU - Hvistendahl, Mark Krogh
AU - Bolognani, Federico
AU - Li, Carrie
AU - Youssef, Nader N
AU - Huh, Susanna
AU - Menys, Alex
AU - Bhatnagar, Gauraang
AU - Vanslembrouck, Ragna
AU - Peeters, Ronald
AU - Sartoris, Riccardo
AU - Vermeersch, Pieter
AU - Wauters, Lucas
AU - Verbeke, Kristin
AU - Jeppesen, Palle Bekker
AU - Joly, Francisca
AU - Vanuytsel, Tim
N1 - Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.
PY - 2024
Y1 - 2024
N2 - BACKGROUND: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide.METHODS: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks).RESULTS: PS volume decreased by -4702 mL/week (-52 %; p < 0.001) at week 52. Seven patients (78 %) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p = 0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p = 0.039), energy absorption by 1134 kJ/day (p = 0.041) and carbohydrate absorption by 56.1 g/day (p = 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p = 0.012), duodenal wall thickness increased by 0.8 mm (p = 0.02) and motility in the proximal colon was reduced (p = 0.031). A total of 127 adverse events was reported, which were mostly mild to moderate.CONCLUSION: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC.CLINICALTRIALS: gov, Number NCT04964986.
AB - BACKGROUND: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide.METHODS: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks).RESULTS: PS volume decreased by -4702 mL/week (-52 %; p < 0.001) at week 52. Seven patients (78 %) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p = 0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p = 0.039), energy absorption by 1134 kJ/day (p = 0.041) and carbohydrate absorption by 56.1 g/day (p = 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p = 0.012), duodenal wall thickness increased by 0.8 mm (p = 0.02) and motility in the proximal colon was reduced (p = 0.031). A total of 127 adverse events was reported, which were mostly mild to moderate.CONCLUSION: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC.CLINICALTRIALS: gov, Number NCT04964986.
KW - Apraglutide
KW - Colon-in-continuity
KW - Glucagon-like peptide-2
KW - Metabolic balance study
KW - Short bowel syndrome
UR - http://www.scopus.com/inward/record.url?scp=85207266241&partnerID=8YFLogxK
U2 - 10.1016/j.clnu.2024.10.011
DO - 10.1016/j.clnu.2024.10.011
M3 - Journal article
C2 - 39461299
SN - 0261-5614
VL - 43
SP - 158
EP - 166
JO - Clinical nutrition (Edinburgh, Scotland)
JF - Clinical nutrition (Edinburgh, Scotland)
IS - 12
ER -