Metabolic Balance Study of Apraglutide in Patients With Short Bowel Syndrome, Intestinal Failure (SBS-IF) and Colon-in-Continuity (CIC)

Phase 2

Completed

Conditions: Short Bowel Syndrome

Interventions: Drug: Apraglutide

Registration Number: NCT04964986

Lead Sponsor: VectivBio AG

Brief Summary: The primary objective of the trial is to evaluate the safety of apraglutide in adult subjects with SBS-IF and CIC.

Detailed Description: This is an international, multicenter trial to evaluate the safety of apraglutide in adult participants with SBS-IF and CIC. The active pharmaceutical ingredient is apraglutide, an investigational glucagon-like peptide-2 (GLP-2) analogue. The trial consists of an evaluation period of 52 weeks.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Signed informed consent for this trial prior to any trial specific assessment.
Male and female subjects with SBS-IF and CIC, receiving parenteral support (PS), secondary to surgical resection of the small intestine with < 200 cm from duodenojejunal flexure.
Subject must require parenteral support (PS) at least 2 days per week and be considered stable.
No restorative surgery intended to change PS requirements in the trial period.
Age ≥ 18 years at screening.

Exclusion Criteria

Pregnancy or lactation.
Body mass index equal or higher than 30 kg/m^2 at the time of screening.
Major abdominal surgery in the last 6 months prior to screening.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Apraglutide	Apraglutide	All participants received apraglutide administered subcutaneously (SC) once weekly for 52 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)	Day 1 up to approximately 55 weeks	A TEAE was any unfavorable and unintended sign, symptom, or disease temporally associated with apraglutide, whether or not related, that occurred or worsened after the dose of apraglutide. A serious TEAE was defined as any TEAE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. Clinically significant changes from baseline in clinical chemistry, hematology, hemostasis, anti-drug antibodies (ADAs), and urine analysis were reported as adverse events. Adverse events of special interest (AESI) included injection site reaction, gastrointestinal obstruction, gallbladder, biliary, and pancreatic disease, fluid overload, colorectal polyps, malignancies.
Absolute Change in Absorption of Energy Over Metabolic Balance (MB) Periods From Baseline at Week 48	Baseline and Week 48	Applicable to Protocol V3.0 implemented in France (classed as secondary endpoint in Protocol V4.0 \[implemented in Belgium\]). The absorption was defined as dietary intake minus output from fecal excretion over a 72-hour MB period at a given analysis time point. Since dietary intake and fecal excretion were measured daily, i.e., up to three measurements may contribute to absorption calculations, the average over all available daily absorption measurements over the 72-hour period were used for analysis.

Secondary Outcome Measures

Name	Time	Method
Relative Change From Baseline in Actual Weekly Parenteral Support (PS) Volume at Weeks 4, 24, and 52	Baseline, Week 4, Week 24, and Week 52	The sum of daily PS volume (including extra fluids) from weekly PS diary data recorded for the corresponding analysis timepoint was used for analysis.
Absolute Change From Baseline in Actual Weekly PS Volume at Weeks 24 and 52	Baseline, Week 24 and Week 52	The sum of daily PS volume (including extra fluids) from weekly PS diary data recorded for the corresponding analysis timepoint was used for analysis.
Number of Participants Who Achieved a Reduction of at Least 1 Day Per Week of PS From Baseline at Weeks 24 and 52	Baseline, Week 24 and Week 52	Participants were considered to have a reduction of at least one day per week of PS from Baseline (incl. extra fluids) if the number of days with PS from weekly PS diary data recorded for the corresponding analysis timepoint was smaller compared to the number of days with PS from weekly PS diary data for Baseline.
Number of Participants Considered Clinical Responders at Weeks 24 and 52	Baseline, Week 24 and 52	Clinical response was defined as a 20% reduction of PS volume from Baseline. The sum of daily PS volume (including extra fluids) from weekly PS diary data recorded for the corresponding analysis timepoint was used for analysis.
Number of Participants Who Achieved Enteral Autonomy at Weeks 24 and 52	Weeks 24 and 52	Enteral autonomy was defined as a participant not receiving PS for hydration or parenteral nutrition (PN) for calories. Participants may have still receive minimal fluid to maintain patency of the central line or for specific elemental/micro-nutrient needs (e.g., \<100 mL fluid for administration of magnesium).
Absolute Change in Total Energy in PN From Baseline at Weeks 24 and 52	Baseline, Week 24 and Week 52	PN was defined as PS that includes protein, carbohydrate, fat, vitamins, and/or trace elements.
Relative Change in Absorption of Energy Over MB Periods From Baseline at Week 48	Baseline and Week 48	The absorption was defined as dietary intake minus output from fecal excretion over a 72-hour MB period at a given analysis time point. Since dietary intake and fecal excretion were measured daily, i.e., up to three measurements may contribute to absorption calculations, the average over all available daily absorption measurements over the 72-hour period were used for analysis.
Change From Baseline in Patient Global Impression of Change (PGIC) at Week 24 and Week 52	Baseline, Week 24 and Week 52	PGIC v2.0 is a single-item questionnaire using a 5-point verbal rating scale, to assess overall change in the participants status after taking the study drug. Response options range from 2= very much better to -2= very much worse.
Change From Baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and Week 52	Baseline, Week 24 and Week 52	This is a three-item questionnaire assessing the impact of PS on the participant's sleep, daily activities, and quality of life (QoL) over the past 7 days. All questions have response options ranging from 0 to 4, not at all to extremely. A reduction from baseline represents a decrease in symptoms.
Secondary: Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 24 and Week 52	Week 24 and Week 52	This form is a single-item questionnaire assessing the participant's satisfaction with the trial medication over the preceding 7 days. Response options range from -2 to 2, very dissatisfied to very satisfied.
Change From Baseline in Patient Global Impression of Satisfaction With Parenteral Support (PGI-SPS) at Week 24 and Week 52	Baseline, Week 24 and Week 52	This is a single-item questionnaire assessing the participant's satisfaction with PS over the preceding 7 days. Response options range from -2 to 2, very dissatisfied to very satisfied. A reduction from baseline represents a decrease in satisfaction.
Trough Apraglutide Plasma Concentration (Ctrough)	Pre-dose on Weeks 2, 4, 12, 24, 32, 40, 48, and 52
Mean Plasma Citrulline Level	Baseline and Weeks 2, 4, 12, 24, 32, 40, 48, and 52
Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 48	Baseline, Week 4 and Week 48	The absorption was defined as dietary intake minus output from fecal excretion over a 72-hour MB period at a given analysis time point. Since dietary intake and fecal excretion were measured daily, i.e., up to three measurements may contribute to absorption calculations, the average over all available daily absorption measurements over the 72-hour period were used for analysis.
Absolute Change in Urine Volume Over MB Periods From Baseline at Week 4 and Week 48	Baseline, Week 4 and Week 48	Based on average daily urine volume data derived as per balance period calculations.
Absolute Change in Absorption of Energy Over MB Periods From Baseline at Week 4	Baseline and Week 4	The absorption was defined as dietary intake minus output from fecal excretion over a 72-hour MB period at a given analysis time point. Since dietary intake and fecal excretion were measured daily, i.e., up to three measurements may contribute to absorption calculations, the average over all available daily absorption measurements over the 72-hour period were used for analysis.
Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48	Baseline, Week 4 and Week 48	Since urinary electrolytes data were measured over the 72-hour MB period, the average of all available results were used for analyses for each MB parameter at a given analysis time point.
Change From Baseline in Pittsburgh Sleep Quality Inventory (PSQI) Total Score at Week 24 and Week 52	Baseline, Week 24 and Week 52	The PSQI is a patient-reported questionnaire used to measure the quality and patterns of sleep, over the past month. The PSQI has seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction over the last month. Minimum Score = 0 (better); Maximum Score = 21 (worse). A negative change from baseline represents an reduction in symptoms.