Introduction

SBS-IF is a severe organ failure with long-term parenteral support (PS) dependence. GLP-2 stimulates intestinal adaptation resulting in increased absorptive capacity. Apraglutide (APRA) is a novel long-acting GLP-2 analog in development for SBS-IF. This multicenter, open-label, phase 2 study in SBS-IF-CiC aims to investigate the safety and clinical efficacy of APRA at 52 weeks (W).

Aims & Methods

STARS Nutrition is a 52W open-label study in 9 adult SBS-IF–CiC pts receiving once-weekly subcutaneous APRA injections (5 mg). Metabolic balance studies were performed at baseline and 4W with stable PS, followed by a 48-W PS adjustment period. During monthly 48-hour fluid balance assessments, oral fluid intake was kept constant by adhering to an individual predefined drinking menu while measuring urine volume. PS was reduced according to an algorithm if an increase in mean daily urinary output of ≥10% was observed. As part of patient-reported outcomes (PRO), Patient Global Impression of Change (PGIC) v2.0 (5-point verbal response scale from 2= much better to -2= much worse) was used to assess overall change in pts’ status since APRA use. Safety was the primary endpoint. Secondary endpoints included changes in weekly PS volume, energy content, and PS days, proportion of clinical responders (≥20% PS reduction) and changes in PGIC at 52W. Data are presented as mean (95% CI) unless otherwise specified. Nominal p-values are calculated using paired T-tests with significance set at 0.05.

Results

APRA had an acceptable safety profile. All pts experienced ≥1 adverse event (AE); a total of 127 AEs were reported. Three pts experienced serious AEs. APRA was interrupted for 1 week in one pt with acute cholangitis and restarted successfully to trial completion. Absolute weekly PS volume decreased significantly by -4702 (-6539 to -2865) mL/week representing a 52% reduction from baseline (p=0.0004). Accordingly, PS energy content significantly decreased by -3510 (-4991 to -2029) kcal/week (p=0.0006). All pts qualified as clinical responders. Seven pts (78%) achieved ≥1 day off PS of whom two pts (22%) reached enteral autonomy. Pts gained an additional 2.1 (0.7–3.6) days off per week. Total body and lean body weight; and daily urine output remained stable despite PS reductions. All pts experienced a subjective improvement of their general condition based on the PGIC: eight pts reported a score of 2 (much better) and one pt reported a score of 1 (little better).

Conclusion

STARS Nutrition prospectively shows evidence for clinical benefit of a long-acting GLP-2 analog in SBS-IF–CiC. APRA has an acceptable safety profile and is associated with significant reductions in PS needs in pts with SBS-IF–CiC resulting in days without PS and subjective improvement based on PRO.

Disclosure

Astrid Verbiest, Mark Krogh Hvistendahl – nothing to declare.
Palle Bekker Jeppesen – received grants/research support/honoraria or consultation fees from Agomab, Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
Francisca Joly – has received grants/research support/honoraria or consultation fees from Agomab, Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
Tim Vanuytsel – has served on the speaker bureau for Abbott, Agomab, Baxter, Biocodex, Dr. Falk Pharma, Fresenius Kabi, Ipsen, Menarini, Microbiotica, MyHealth, Remedus, Takeda, Truvion, VectivBio and Zealand Pharma. TV has provided clinical advice to Baxter, Danone, Dr. Falk Pharma, MyHealth, NorthSea Therapeutics, Shire, Therachon, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Danone, MyHealth, Takeda and VectivBio.
Federico Bolognani, Carrie Li and Nader N. Youssef – employees of VectivBio/Ironwood.
This research was supported by VectivBio AG/Ironwood.