Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as TA799
Apraglutide · 6 trials · 5 indications
System organ class, frequency and severity
Clinical Chemistry panel of analytes will be examined for clinically significant changes.
Hematology panel of analytes will be examined for clinically significant changes.
Hemostasis INR will be examined for clinically significant changes.
Urinanalysis panel of analytes will be examined for clinically significant changes.
* Systolic and diastolic blood pressure in mmHg will be examined for clinically significant changes. * Heart rate in Beats per Minute (BPM) will be examined for clinically significant changes.
ECG; intervals and rhythm
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.
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.
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a lower limit of quantification (LLOQ) of 1 ng/mL and an upper limit of 200 ng/mL. Plasma pharmacokinetic (PK) parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. AUCinf was calculated as: AUCinf = AUC from time zero to the last quantifiable concentration (AUClast) + (Clast/kel) where Clast was the observed concentration at the last time point with concentrations above the lower limit of quantification and kel was the terminal elimination rate constant.
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used.
Apraglutide was quantified in human plasma samples using a fully validated liquid chromatography mass spectrometry-based method, with a LLOQ of 1 ng/mL and an upper limit of 200 ng/mL. Plasma PK parameters for apraglutide were estimated using non-compartmental methods from the concentration-time profiles. Actual sampling times, rather than scheduled sampling times, were used. Cmax was the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units.
Pharmacokinetic (PK) samples collected for the measurement of plasma concentration of apraglutide were analyzed using a validated analytical method in compliance with applicable standard operating procedures.
PK samples collected for the measurement of plasma concentration of apraglutide were analyzed using a validated analytical method in compliance with applicable standard operating procedures.
| Arm | Type | Description |
|---|---|---|
| Active | EXPERIMENTAL | Apraglutide subcutaneous (SC) injections, once weekly |
| Placebo | PLACEBO_COMPARATOR | Placebo SC injections, once weekly |
| Apraglutide subcutaneous (SC) injections, once weekly | EXPERIMENTAL | Peptide analogue of Glucagon-like Peptide 2 (GLP-2) |
| Apraglutide SC injections, once weekly | EXPERIMENTAL | Peptide analogue of GLP-2 |
| Apraglutide | EXPERIMENTAL | All participants received apraglutide administered subcutaneously (SC) once weekly for 52 weeks. |
| Part 1: Moderate hepatic impairment | EXPERIMENTAL | Child-Pugh B |
| Part 1: Normal hepatic function | EXPERIMENTAL | - |
| Part 2: Mild hepatic impairment | EXPERIMENTAL | Child-Pugh A |
| Severe Renal Impairment | EXPERIMENTAL | eGFR (mL/min/1.73 m2): \<30 not on hemodialysis |
| Normal Healthy Match | EXPERIMENTAL | eGFR (mL/min/1.73 m2): ≥90 |
| Moderate Renal Impairment | EXPERIMENTAL | eGFR (mL/min/1.73 m2): ≥30 to 60 |
| Mild Renal Impairment | EXPERIMENTAL | eGFR (mL/min/1.73 m2): ≥60 to 90 |
| Name | Type | Description |
|---|---|---|
| Apraglutide | DRUG | Apraglutide is a synthetic peptide analogue of glucagon-like peptide-2 (GLP-2), which acts as a full agonist at the GLP-2 receptor with in vitro potency and selectivity comparable with native GLP-2. Participants will be administered or will self-administer a weekly SC injection of apraglutide. |
| Placebo | DRUG | Participants will be administered or will self-administer a weekly single SC injection of placebo in the matching injection volumes. |
Inclusion Criteria: * Participant must be ≥18 years of age, at the time of signing the informed consent. * Male and female participants with SBS-IF, receiving PS secondary to surgical resection of the small intestine with residual length ≥10 cm to \<200 cm from duodeno-jejunal flexure, based on ava...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 3 | PHASE3 | Teduglutide |
| Ironwood Pharmaceuticals, Inc. Class A | IRWD | 2 | PHASE3 | Apraglutide |
| Jaguar Health, Inc. | JAGX | 1 | PHASE2 | Crofelemer |
Apraglutide is an investigational small molecule developed by Ironwood Pharmaceuticals, Inc. (ticker IRWD) for Short Bowel Syndrome, Chronic Kidney Disease, and Hepatic Impairment. It is a peptide in the -tide class that acts on the GLP-2 receptor. It is not approved and remains in clinical development.
Apraglutide is being studied for Short Bowel Syndrome, including Short Bowel Syndrome associated with Intestinal Failure (SBS-IF). Clinical trials have enrolled adults 18 years and older with these conditions. It is investigational and has not been approved for any indication.
Apraglutide targets the GLP-2 receptor, also known as GLP-2R. It is a peptide belonging to the -tide class, and its activity at this receptor is the basis for its development in Short Bowel Syndrome and related intestinal conditions.
Apraglutide is developed by Ironwood Pharmaceuticals, Inc., which trades under the ticker IRWD. The company is running the clinical program across Short Bowel Syndrome, Chronic Kidney Disease, and Hepatic Impairment.
Apraglutide is in clinical development and is not FDA approved. Its program includes Phase 1, Phase 2, and Phase 3 trials. Four trials have been recorded, with two currently active and two completed, enrolling a total of 456 participants.
Apraglutide trials include NCT07742735, a recruiting Phase 3 study in Short Bowel Syndrome with Intestinal Failure, and NCT05018286, an active Phase 3 long-term safety extension in Short Bowel Syndrome. Completed studies include NCT05706623 in hepatic impairment and NCT04964986 in SBS-IF with colon-in-continuity.