Short Bowel Syndrome
Conditions
Keywords
Intestinal Failure, SBS, SBS-IF, CIC, Colon-in-Continuity
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.
Interventions
DRUGApraglutide
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.
Sponsors
VectivBio AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Mean Plasma Citrulline Level | Baseline and Weeks 2, 4, 12, 24, 32, 40, 48, and 52 | — |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Trough Apraglutide Plasma Concentration (Ctrough) | Pre-dose on Weeks 2, 4, 12, 24, 32, 40, 48, and 52 | — |
Countries
Belgium, France
Participant flow
Pre-assignment details
Of the 10 participants with SBS-IF and CIC enrolled, 9 participants were treated and analyzed. The participant who enrolled but was not treated was not included in any study analysis.
Participants by arm
| Arm | Count |
|---|---|
| Apraglutide SC Injections, Once Weekly All participants received apraglutide administered subcutaneously (SC) once weekly for 52 weeks. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Apraglutide SC Injections, Once Weekly |
|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 17.46 |
| Age, Customized 18-64 years | 8 Participants |
| Age, Customized 65-84 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized White | 9 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 3 / 9 |
Outcome results
Primary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Absolute Change in Absorption of Energy Over Metabolic Balance (MB) Periods From Baseline at Week 48 | 1133.963 kJ/day | Standard Deviation 1399.8793 |
p-value: 0.041paired t-test
Primary
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | At least one TEAE | 9 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | At least one treatment-related TEAE | 5 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | At least one TESAE | 3 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | At least one treatment-related TESAE | 1 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | At least one treatment-emergent AESI | 3 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | At least one TEAE leading to dose interruption | 1 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | At least one TEAE leading to permanent dose discontinuation | 0 Participants |
Secondary
Absolute Change From Baseline in Actual Weekly PS Volume at Weeks 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 24 and Week 52
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Absolute Change From Baseline in Actual Weekly PS Volume at Weeks 24 and 52 | Week 24 | -3510.000 mL | Standard Deviation 1893.7859 |
| Apraglutide SC Injections, Once Weekly | Absolute Change From Baseline in Actual Weekly PS Volume at Weeks 24 and 52 | Week 52 | -4701.778 mL | Standard Deviation 2389.9652 |
Comparison: Week 24p-value: <0.001paired t-test
Comparison: Week 52p-value: <0.001paired t-test
Secondary
Absolute Change in Absorption of Energy Over MB Periods From Baseline at 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.
Time frame: Baseline and Week 4
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Absolute Change in Absorption of Energy Over MB Periods From Baseline at Week 4 | 494.259 kJ/day | Standard Deviation 1355.5857 |
p-value: 0.306paired t-test
Secondary
Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 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, Week 4 and Week 48
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 48 | Fat - Week 4 | 247.281 kJ/day | Standard Deviation 661.1866 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 48 | Fat - Week 48 | 406.741 kJ/day | Standard Deviation 776.4802 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 48 | Carbohydrate - Week 4 | 272.881 kJ/day | Standard Deviation 675.1125 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 48 | Carbohydrate - Week 48 | 877.011 kJ/day | Standard Deviation 945.2279 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 48 | Protein - Week 4 | 176.178 kJ/day | Standard Deviation 280.0788 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Absorption of Macronutrients Over MB Periods From Baseline at Weeks 4 and 48 | Protein - Week 48 | 194.400 kJ/day | Standard Deviation 285.2597 |
Comparison: Fat absorption increase at Week 4p-value: 0.294paired t-test
Comparison: Fat absorption increase at Week 48p-value: 0.155paired t-test
Comparison: Carbohydrate absorption at Week 4p-value: 0.26paired t-test
Comparison: Carbohydrate absorption at Week 48p-value: 0.024paired t-test
Comparison: Protein absorption at Week 4p-value: 0.096paired t-test
Comparison: Protein absorption at Week 48p-value: 0.075paired t-test
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Absolute Change in Total Energy in PN From Baseline at Weeks 24 and 52 | Week 24 | -2763.889 kcal | Standard Deviation 1830.8065 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Total Energy in PN From Baseline at Weeks 24 and 52 | Week 52 | -3510.111 kcal | Standard Deviation 1927.2066 |
Comparison: Week 24p-value: 0.002paired t-test
Comparison: Week 52p-value: <0.001paired t-test
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Calcium - Week 4 | 0.1444 cmol/L | Standard Deviation 1.09818 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Calcium - Week 48 | -0.5532 cmol/L | Standard Deviation 2.28264 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Magnesium - Week 4 | -0.258 cmol/L | Standard Deviation 0.837 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Magnesium - Week 48 | -2.306 cmol/L | Standard Deviation 3.14 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Sodium - Week 4 | 31.668 cmol/L | Standard Deviation 24.1946 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Sodium - Week 48 | 17.097 cmol/L | Standard Deviation 50.1676 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Potassium - Week 4 | 2.047 cmol/L | Standard Deviation 16.8154 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Potassium - Week 48 | -8.012 cmol/L | Standard Deviation 13.5798 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Urea - Week 4 | 7.693 cmol/L | Standard Deviation 59.259 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Urea - Week 48 | -89.649 cmol/L | Standard Deviation 77.9786 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Creatinine - Week 4 | 0.198 cmol/L | Standard Deviation 1.0071 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urinary Electrolytes Over MB Periods From Baseline at Week 4 and Week 48 | Creatinine - Week 48 | -0.011 cmol/L | Standard Deviation 1.3283 |
Comparison: Calcium, Week 4p-value: 0.70495% CI: [-0.7887, 0.8748]paired t-test
Comparison: Calcium, Week 48p-value: 0.48895% CI: [-2.7442, 0.8896]paired t-test
Comparison: Magnesium, Week 4p-value: 0.38295% CI: [-0.896, 0.313]paired t-test
Comparison: Magnesium, Week 48p-value: 0.05995% CI: [-5.279, -0.165]paired t-test
Comparison: Sodium, Week 4p-value: 0.00495% CI: [5.51, 51.861]paired t-test
Comparison: Sodium, Week 48p-value: 0.33795% CI: [-27.758, 55.828]paired t-test
Comparison: Potassium, Week 4p-value: 0.72495% CI: [-11.87, 14.931]paired t-test
Comparison: Potassium, Week 48p-value: 0.11595% CI: [-18.88, 3.737]paired t-test
Comparison: Urea, Week 4p-value: 0.70795% CI: [-39.551, 52.617]paired t-test
Comparison: Urea, Week 48p-value: 0.00995% CI: [-159.956, -20.068]paired t-test
Comparison: Creatinine, Week 4p-value: 0.57295% CI: [-0.649, 0.96]paired t-test
Comparison: Creatinine, Week 48p-value: 0.98195% CI: [-1.06, 1.073]paired t-test
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urine Volume Over MB Periods From Baseline at Week 4 and Week 48 | Week 4 | 246.889 mL/day | Standard Deviation 343.3609 |
| Apraglutide SC Injections, Once Weekly | Absolute Change in Urine Volume Over MB Periods From Baseline at Week 4 and Week 48 | Week 48 | -178.556 mL/day | Standard Deviation 299.5613 |
Comparison: Week 4p-value: 0.063paired t-test
Comparison: Week 48p-value: 0.112paired t-test
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point. Participants with an assessment at given time point.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Change (PGIC) at Week 24 and Week 52 | Week 24 | 2 (Much Better) | 6 Participants |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Change (PGIC) at Week 24 and Week 52 | Week 24 | 1 (A Little Better) | 2 Participants |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Change (PGIC) at Week 24 and Week 52 | Week 52 | 2 (Much Better) | 8 Participants |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Change (PGIC) at Week 24 and Week 52 | Week 52 | 1 (A Little Better) | 1 Participants |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and Week 52 | Sleep Impact: Week 24 | -0.40 score on a scale | Standard Deviation 1.517 |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and Week 52 | Sleep Impact: Week 52 | -0.50 score on a scale | Standard Deviation 1.291 |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and Week 52 | Daily Activities Impact: Week 24 | -0.80 score on a scale | Standard Deviation 1.643 |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and Week 52 | Daily Activities Impact: Week 52 | -1.00 score on a scale | Standard Deviation 1.414 |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and Week 52 | QoL Impact: Week 24 | -1.40 score on a scale | Standard Deviation 1.14 |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and Week 52 | QoL Impact: Week 52 | -1.25 score on a scale | Standard Deviation 0.957 |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point. Partcipants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Satisfaction With Parenteral Support (PGI-SPS) at Week 24 and Week 52 | Week 24 | -0.20 score on a scale | Standard Deviation 0.447 |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Patient Global Impression of Satisfaction With Parenteral Support (PGI-SPS) at Week 24 and Week 52 | Week 52 | 0.00 score on a scale | Standard Deviation 0 |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Pittsburgh Sleep Quality Inventory (PSQI) Total Score at Week 24 and Week 52 | Week 24 | -1.89 score on a scale | Standard Deviation 2.667 |
| Apraglutide SC Injections, Once Weekly | Change From Baseline in Pittsburgh Sleep Quality Inventory (PSQI) Total Score at Week 24 and Week 52 | Week 52 | -1.56 score on a scale | Standard Deviation 1.509 |
Comparison: Week 24p-value: 0.066paired t-test
Comparison: Week 52p-value: 0.015paired t-test
Secondary
Mean Plasma Citrulline Level
Time frame: Baseline and Weeks 2, 4, 12, 24, 32, 40, 48, and 52
Population: The safety analysis set included all participants exposed to trial medication. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Week 40 | 17.860 μmol/L | Standard Deviation 15.802 |
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Baseline | 11.571 μmol/L | Standard Deviation 9.7091 |
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Week 2 | 13.516 μmol/L | Standard Deviation 9.8136 |
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Week 4 | 15.531 μmol/L | Standard Deviation 12.4055 |
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Week 12 | 14.860 μmol/L | Standard Deviation 12.2165 |
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Week 24 | 14.810 μmol/L | Standard Deviation 11.8877 |
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Week 32 | 14.994 μmol/L | Standard Deviation 12.688 |
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Week 48 | 16.638 μmol/L | Standard Deviation 14.9346 |
| Apraglutide SC Injections, Once Weekly | Mean Plasma Citrulline Level | Week 52 | 14.714 μmol/L | Standard Deviation 11.7896 |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Number of Participants Considered Clinical Responders at Weeks 24 and 52 | Week 24 | 7 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Considered Clinical Responders at Weeks 24 and 52 | Week 52 | 9 Participants |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Achieved a Reduction of at Least 1 Day Per Week of PS From Baseline at Weeks 24 and 52 | Week 24 | 5 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Achieved a Reduction of at Least 1 Day Per Week of PS From Baseline at Weeks 24 and 52 | Week 52 | 7 Participants |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Achieved Enteral Autonomy at Weeks 24 and 52 | Week 24 | 0 Participants |
| Apraglutide SC Injections, Once Weekly | Number of Participants Who Achieved Enteral Autonomy at Weeks 24 and 52 | Week 52 | 2 Participants |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Relative Change From Baseline in Actual Weekly Parenteral Support (PS) Volume at Weeks 4, 24, and 52 | Week 4 | -0.73 percentage change in PS volume | Standard Deviation 2.709 |
| Apraglutide SC Injections, Once Weekly | Relative Change From Baseline in Actual Weekly Parenteral Support (PS) Volume at Weeks 4, 24, and 52 | Week 24 | -39.99 percentage change in PS volume | Standard Deviation 22.588 |
| Apraglutide SC Injections, Once Weekly | Relative Change From Baseline in Actual Weekly Parenteral Support (PS) Volume at Weeks 4, 24, and 52 | Week 52 | -52.44 percentage change in PS volume | Standard Deviation 29.192 |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Relative Change in Absorption of Energy Over MB Periods From Baseline at Week 48 | 29.23 percentage change | Standard Deviation 36.898 |
Secondary
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
Population: The full analysis set included all participants who received at least one dose of trial treatment and contributed at least one valid post-baseline efficacy point. Participants with an assessment at given time point.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Secondary: Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 24 and Week 52 | Week 24 | 2 (Very Satisfied) | 5 Participants |
| Apraglutide SC Injections, Once Weekly | Secondary: Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 24 and Week 52 | Week 24 | 1 (Satisfied) | 3 Participants |
| Apraglutide SC Injections, Once Weekly | Secondary: Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 24 and Week 52 | Week 52 | 2 (Very Satisfied) | 3 Participants |
| Apraglutide SC Injections, Once Weekly | Secondary: Patient Global Impression of Treatment Satisfaction (PGI-TS) at Week 24 and Week 52 | Week 52 | 1 (Satisfied) | 6 Participants |
Secondary
Trough Apraglutide Plasma Concentration (Ctrough)
Time frame: Pre-dose on Weeks 2, 4, 12, 24, 32, 40, 48, and 52
Population: The safety analysis set included all participants exposed to trial medication. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Apraglutide SC Injections, Once Weekly | Trough Apraglutide Plasma Concentration (Ctrough) | Week 2 | 1.928 ng/mL | Standard Deviation 0.7058 |
| Apraglutide SC Injections, Once Weekly | Trough Apraglutide Plasma Concentration (Ctrough) | Week 4 | 1.217 ng/mL | Standard Deviation 0.2902 |
| Apraglutide SC Injections, Once Weekly | Trough Apraglutide Plasma Concentration (Ctrough) | Week 12 | 1.934 ng/mL | Standard Deviation 0.6665 |
| Apraglutide SC Injections, Once Weekly | Trough Apraglutide Plasma Concentration (Ctrough) | Week 24 | 2.863 ng/mL | Standard Deviation 1.0668 |
| Apraglutide SC Injections, Once Weekly | Trough Apraglutide Plasma Concentration (Ctrough) | Week 32 | 1.739 ng/mL | Standard Deviation 0.6805 |
| Apraglutide SC Injections, Once Weekly | Trough Apraglutide Plasma Concentration (Ctrough) | Week 40 | 2.386 ng/mL | Standard Deviation 0.9587 |
| Apraglutide SC Injections, Once Weekly | Trough Apraglutide Plasma Concentration (Ctrough) | Week 48 | 3.810 ng/mL | Standard Deviation 1.1031 |
| Apraglutide SC Injections, Once Weekly | Trough Apraglutide Plasma Concentration (Ctrough) | Week 52 | 2.678 ng/mL | Standard Deviation 1.4039 |