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 study investigated the safety and efficacy of APRA in patients with SBS-IF and CiC.

Aims & Methods

STARS Nutrition is a 52-Week (W) multicenter, open-label, phase 2 study in 9 adult SBS-IF-CiC patients (pts) receiving weekly subcutaneous APRA injections (5mg). 72-h metabolic balance studies (MBS) were performed at baseline (BL), 4W and 48W; with stable PS at BL and 4W. During MBS, oral fluid intake was kept constant by adhering to an individual predefined drinking menu. Duplicates of meals and fluids (wet weight intake) were collected as well as urine and feces (fecal wet weight output). Pts were advised to keep oral food intake at 4W similar to BL, but not at 48W to explore the effect of APRA on spontaneous dietary intake. Safety was the primary endpoint. Secondary endpoints included changes in wet weight, energy and macronutrient absorption at 4W and 48W. Data are presented as mean (95% CI) unless specified otherwise. Nominal p-values are calculated using paired T-tests with significance set at 0.05.

Results

Small bowel length was 19 (range 0-50) cm and median estimated residual colon was 79 (range 43-100) %. At BL, pts received a PS volume of 10 (range 4-21) L/W. APRA had an acceptable safety profile. At 4W, fecal output reduced significantly by 253 (68 – 437) g/day (p=0.013); resulting in a trend to increased wet weight absorption of 256 (-9 – 520) g/day (p=0.057) while energy absorption remained unaltered. At 48W, pts significantly increased their overall wet weight intake (p=0.047), carbohydrate (p=0.042) and nitrogen intake (p=0.024) resulting in a significantly increased energy intake (p=0.027). Fecal wet weight output remained constant despite the increased oral intake. There was a significant increase in wet weight absorption by 316 (21 – 611) g/day (p=0.039), energy absorption by 1134 (58 – 2210) kJ/day (p=0.041) and carbohydrate absorption by 56.1 (8.8 – 94.3) g/day (p= 0.024). Urine output and body weight remained stable throughout the study.

Conclusion

The STARS Nutrition MBS findings confirm the role of the colon in energetic recovery of carbohydrates and maintenance of the fluid balance in SBS-IF-CiC. In pts with SBS-IF-CiC, APRA treatment resulted in an early reduced fecal output and improved wet weight absorption. After 48 weeks, oral intake was increased despite stable fecal output, leading to increased energy and carbohydrate absorption.

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.