A Study of Teduglutide in Japanese Children With Short Bowel Syndrome Who Are 4 Months or Older

Study Overview
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Brief Summary
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The main aims of the study are to check for side effects from teduglutide. Participants will receive a daily injection of teduglutide just under the skin (subcutaneous) for 24 weeks. Then they are followed up for another 4 weeks. Participants may be able to repeat this treatment if they meet specific criteria. The study doctors will check for side effects from teduglutide until it becomes commercially available. The maximum duration of treatment is approximately 18 months.

Detailed Description
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A study of teduglutide in Japanese children with short bowel syndrome who are 4 months or older.

Official Title
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A Phase 3, Open-label Safety Study of Teduglutide in Japanese Pediatric Patients With Short Bowel Syndrome Who Are Dependent on Parenteral Support, Aged 4 Months of Corrected Gestational Age or Older, and Requiring the Dosing of 1.25 mg Formulation

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Teduglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female pediatric patient of corrected gestational age 4 months or older. Body weight at the time of screening and baseline visits of at least 5 kg and <10 kg for participants with normal renal function or mild renal impairment (estimated glomerular filtration rate >=50 mL/min/1.73 m^2), OR at least 10 kg and <20 kg for participants with moderate or greater renal impairment (estimated glomerular filtration rate <50 mL/min/1.73 m^2). Diagnosis of short bowel syndrome (SBS) with intestinal failure, defined as dependence on PS to provide at least 30% of fluid or caloric needs. Participants to have stable PS for at least 1 month prior to screening as assessed by the investigator. Stable PS is defined as inability to significantly reduce parenteral nutrition/intravenous fluid (PN/IV) support, usually associated with minimal or no advance in enteral feeds (ie, 10% or less change in PN or advance in feeds), assessed by the investigator. Exclusion Criteria: A parent/guardian who is not capable of understanding or not willing to adhere to the study visit schedule and other protocol requirements. Clinically significant intestinal obstruction, active or recurrent pancreatic or biliary disease, or dysmotility that prevents the advancement of enteral intake. Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, etc. Severe, known dysmotility syndrome, such as pseudo-obstruction or persistent, severe, active gastroschisis-related dysmotility, that is the primary contributing factor to feeding intolerance and inability to reduce PS, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding. Major gastrointestinal (GI) surgical intervention including significant intestinal resection or bowel lengthening procedure within 3 months prior to screening (insertion of feeding tube, anastomotic ulcer repair, minor intestinal resections =<10 cm and endoscopic procedures are allowed). Cardiac disease that makes the patient vulnerable to changes in fluid status. History of cancer or known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of GI cancer (including hepatobiliary and pancreatic cancer). Concurrent treatment with glucagon-like peptide-2 (GLP-2), human growth hormone, or analogs of these hormones within 6 months prior to the screening visit, or concurrent treatment with octreotide, or GLP-1 analogs within 30 days prior to the screening visit. Concurrent treatment with biological therapy (eg, anti-tumor necrosis factor [anti-TNF]) for active Crohn's disease within 6 months prior to the screening visit. Participation in a clinical study using an experimental drug (other than glutamine or omegaven) within 3 months or 5.5 half-lives of the experimental drug, whichever is longer, prior to the screening visit and for the duration of the study. Known or suspected intolerance or hypersensitivity to the study drug, closely related compounds, or any of the stated ingredients. Signs of active, severe, or unstable clinically significant hepatic impairment during the screening period as meeting at least 2 of any of the following parameters: International normalized ratio >1.5 not corrected with parenteral vitamin K Platelet count <100×10^3/mcrL due to portal hypertension Presence of clinically significant gastric or esophageal varices Cirrhosis Persistent cholestasis defined as conjugated bilirubin >4 mg/dL (>68 mcr mol/L) over a 2-week period during screening Total bilirubin >=2x upper limit of normal (ULN) Aspartate aminotransferase (AST) >=3x ULN Alanine aminotransferase (ALT) >=3x ULN

Ages Eligible for Study
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Minimum Age: 4 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teduglutide 0.05 milligram per kilogram (mg/kg)<br>Participants will receive teduglutide 0.05 mg/kg (0.025 mg/kg for participants with moderate or greater renal impairment) subcutaneous (SC) injection once daily for 24 weeks followed by no treatment period for 4 weeks. The maximum duration of treatment is approximately 18 months. | Drug: Teduglutide<br>* Teduglutide 0.05 mg/kg SC injection<br>* Other names: TAK-633;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An AE is defined as any untoward medical occurrence in a clinical investigation subject administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as any AEs whose onset occurred, severity worsened, or intensity increased after receiving the investigational product. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Number of Participants With Serious Adverse Events (SAEs) | An SAE is defined as any untoward medical occurrence that at any dose: Results in death, Is life threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Leads to a congenital anomaly /birth defect, Is the other important medical event. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Number of Participants With Adverse Events of Special Interest (AESIs) | An AESI, whether serious or non-serious, is one of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as an Adverse Event | Vital signs include systolic and diastolic blood pressure, heart rate and body temperature. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Change From Baseline in Z-Score of Body Weight | The Z-score indicates the number of standard deviations away from the mean. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Change From Baseline in Z-Score of Height | The Z-score indicates the number of standard deviations away from the mean. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Change From Baseline in Z-Score of Head Circumference | The Z-score indicates the number of standard deviations away from the mean. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Change From Baseline in Z-Score of Weight-for-Length | The Z-score indicates the number of standard deviations away from the mean. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Number of Participants With Clinically Significant Laboratory Safety Data Reported as an Adverse Event | Laboratory safety data includes biochemistry, hematology and urinalysis. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Number of Participants With Significant Change in Urine Output Reported as an Adverse Event | Urine and stool output will be recorded and calculated in the output diary over a 48-hour period of parenteral support (PS) and enteral nutrition (EN) stability before every site visit and within 1 week of implementing a change in the PS prescription. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 
| Number of Participants With Significant Change in Stool Output Reported as an Adverse Event | Urine and stool output will be recorded and calculated in the output diary over a 48-hour period of PS and EN stability before every site visit and within 1 week of implementing a change in the PS prescription. | From start of study drug administration up to end of study (EOS) (up to Week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in PS Volume | PS (parenteral nutrition or intravenous fluids) will be considered for managing nutritional support in terms of volume and calories during the treatment period. | Baseline, multiple timepoints after dose (Week 1, 2, 4, 8, 12, 16, 20, 24, and 28), and end of study (EOS: up to Week 28) | 
| Percent Change From Baseline in PS Volume | Percent change from baseline in PS volume will be calculated as follows; (PS volume at each point [Week 1, 2, 4, 8, 12, 16, 20, 24, and 28] - PS volume at baseline)/ PS volume at baseline *100 (percent). PS (parenteral nutrition or intravenous fluids) will be considered for managing nutritional support in terms of volume and calories during the treatment period. | Baseline, multiple timepoints after dose (Week 1, 2, 4, 8, 12, 16, 20, 24, and 28), and end of study (EOS: up to Week 28) | 
| Number of Participants who Demonstrate at least 20 Percent (%) Reduction From Baseline in PS Volume | PS (parenteral nutrition or intravenous fluids) will be considered for managing nutritional support in terms of volume and calories during the treatment period. | Baseline, multiple timepoints after dose (Week 1, 2, 4, 8, 12, 16, 20, 24, and 28), and end of study (EOS: up to Week 28) | 
| Number of Participants who Achieved Enteral Autonomy | Achieving enteral autonomy is defined as complete weaning off PS. PS (parenteral nutrition or intravenous fluids) will be considered for managing nutritional support in terms of volume and calories during the treatment period. Number of participants who achieved enteral autonomy at each time will be reported. | Baseline, multiple timepoints after dose (Week 1, 2, 4, 8, 12, 16, 20, 24, and 28), and end of study (EOS: up to Week 28) | 
| Change in Days per Week of PS | PS (parenteral nutrition or intravenous fluids) will be considered for managing nutritional support in terms of volume and calories during the treatment period. | Baseline, multiple timepoints after dose (Week 1, 2, 4, 8, 12, 16, 20, 24, and 28), and end of study (EOS: up to Week 28) |