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

VectivBio AG10 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Short Bowel Syndrome

Interventions

ApraglutideDRUG

Apraglutide is a synthetic peptide analogue of GLP-2 under development for treatment of SBS-IF, which acts as a full agonist at the GLP-2 receptor with in vitro potency and selectivity comparable with native GLP-2.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (2)

UZ Leuven

Leuven, Belgium

Beaujon Hospital

Clichy, France

Outcomes

Primary Outcomes

Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)

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.

Time frame: Day 1 up to approximately 55 weeks

Absolute Change in Absorption of Energy Over Metabolic Balance (MB) Periods From Baseline at 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.

Time frame: Baseline and Week 48

Secondary Outcomes

Relative Change From Baseline in Actual Weekly Parenteral Support (PS) Volume at Weeks 4, 24, and 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.

Time frame: Baseline, Week 4, Week 24, and Week 52

Absolute Change From Baseline in Actual Weekly PS Volume at Weeks 24 and 52

Data from ClinicalTrials.gov

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The sum of daily PS volume (including extra fluids) from weekly PS diary data recorded for the corresponding analysis timepoint was used for analysis.

Time frame: Baseline, Week 24 and Week 52

Number of Participants Who Achieved a Reduction of at Least 1 Day Per Week of PS From Baseline at Weeks 24 and 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.

Time frame: Baseline, Week 24 and Week 52

Number of Participants Considered Clinical Responders at Weeks 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.

Time frame: Baseline, Week 24 and 52

Number of Participants Who Achieved Enteral Autonomy at 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).

Time frame: Weeks 24 and 52

Absolute Change in Total Energy in PN From Baseline at Weeks 24 and 52

PN was defined as PS that includes protein, carbohydrate, fat, vitamins, and/or trace elements.

Time frame: Baseline, Week 24 and Week 52

Relative Change in Absorption of Energy Over MB Periods From Baseline at 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.

Time frame: Baseline and Week 48

Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 48

Time frame: Baseline, Week 4 and Week 48

Absolute Change in Urine Volume Over MB Periods From Baseline at Week 4 and Week 48

Based on average daily urine volume data derived as per balance period calculations.

Time frame: Baseline, Week 4 and Week 48

Absolute Change in Absorption of Energy Over MB Periods From Baseline at Week 4

Time frame: Baseline and Week 4

Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at 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.

Time frame: Baseline, Week 4 and Week 48

Change From Baseline in Pittsburgh Sleep Quality Inventory (PSQI) Total Score at 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.

Time frame: Baseline, Week 24 and Week 52

Change From Baseline in Patient Global Impression of Change (PGIC) at 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.

Time frame: Baseline, Week 24 and Week 52

Secondary: Patient Global Impression of Treatment Satisfaction (PGI-TS) at 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.

Time frame: Week 24 and Week 52

Change From Baseline in Patient Global Impression of Satisfaction With Parenteral Support (PGI-SPS) at 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.

Time frame: Baseline, Week 24 and Week 52

Change From Baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at 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.

Time frame: Baseline, Week 24 and Week 52

Trough Apraglutide Plasma Concentration (Ctrough)

Time frame: Pre-dose on Weeks 2, 4, 12, 24, 32, 40, 48, and 52

Mean Plasma Citrulline Level

Time frame: Baseline and Weeks 2, 4, 12, 24, 32, 40, 48, and 52