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

Short Bowel Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05027308
• Other study ID #: TAK-633-3008
• Secondary ID: U1111-1267-3327j
• Status: Completed
• Phase: Phase 3
• Start date: January 4, 2022
• Est. completion date: September 27, 2023

Study information

• Verified date: May 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 51.3 weeks.

Description:

A study of teduglutide in Japanese children with short bowel syndrome aged 4 months or older.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3
• Est. completion date: September 27, 2023
• Est. primary completion date: September 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Months and older

Eligibility

Inclusion Criteria:

1. Male or female pediatric patient of corrected gestational age 4 months or older.

2. 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).

3. Diagnosis of short bowel syndrome (SBS) with intestinal failure, defined as dependence on PS to provide at least 30% of fluid or caloric needs.

4. 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:

1. A parent/guardian who is not capable of understanding or not willing to adhere to the study visit schedule and other protocol requirements.

2. Clinically significant intestinal obstruction, active or recurrent pancreatic or biliary disease, or dysmotility that prevents the advancement of enteral intake.

3. Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, etc.

4. 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.

5. 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).

6. Cardiac disease that makes the patient vulnerable to changes in fluid status.

7. 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).

8. 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.

9. 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.

10. 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.

11. Known or suspected intolerance or hypersensitivity to the study drug, closely related compounds, or any of the stated ingredients.

12. 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:

1. International normalized ratio >1.5 not corrected with parenteral vitamin K

2. Platelet count <100×10^3/mcrL due to portal hypertension

3. Presence of clinically significant gastric or esophageal varices

4. Cirrhosis

5. Persistent cholestasis defined as conjugated bilirubin >4 mg/dL (>68 mcr mol/L) over a 2-week period during screening

6. Total bilirubin >=2x upper limit of normal (ULN)

7. Aspartate aminotransferase (AST) >=3x ULN

8. Alanine aminotransferase (ALT) >=3x ULN

Related Conditions & MeSH terms

• Short Bowel Syndrome
• Syndrome

Intervention

Drug:
• Teduglutide
Teduglutide 0.05 mg/kg SC injection

Locations

Country	Name	City	State
Japan	Akita University Hospital	Akita
Japan	Kyushu University Hospital	Fukuoka
Japan	Kagoshiha University Hospital	Kagoshima
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Showa University Hospital	Shinagawa-ku	Tokyo
Japan	University of Tsukuba Hospital	Tsukuba	Ibaraki

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An AE is defined as any untoward medical occurrence in a clinical investigation participant 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 first dose of study drug until follow-up visit (4 weeks after end of treatment [EOT]/end of termination [ET] {up to 47.3-51.3 weeks})
Primary	Number of Participants With Serious Adverse Events (SAEs)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. 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 first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
Primary	Number of Participants With Adverse Events of Special Interest (AESIs)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. 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 first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
Primary	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 first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
Primary	Change From Baseline in Body Weight Z-Score at EOT	A Z-score is the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). According to WHO Child Growth Standards used for assessment of this outcome measure, a weight for age Z-score below -2 indicates underweight.	Baseline, EOT (up to 47.3-51.3 weeks)
Primary	Change From Baseline in Height Z-Score at EOT	A Z-score is the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). According to WHO Child Growth Standards used for assessment of this outcome measure, a height for age Z-score below -2 indicates stunted.	Baseline, EOT (up to 47.3-51.3 weeks)
Primary	Change From Baseline in Head Circumference Z-Score at EOT	A Z-score is the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). According to the Food and Nutrition Technical Assistance (FANTA) Guide to Anthropometry used for assessment of this outcome measure, a head circumference for age Z-score below -2 indicates small head circumference.	Baseline, EOT (up to 47.3-51.3 weeks)
Primary	Change From Baseline in Weight-for-Length Z-Score at EOT	A Z-score is the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the reference population. Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). According to WHO Child Growth Standards used for assessment of this outcome measure, a weight for length Z-score below -2 indicates wasted (recent and severe weight loss).	Baseline, EOT (up to 47.3-51.3 weeks)
Primary	Number of Participants With Any Laboratory Safety Finding Reported as an Adverse Event	Laboratory safety parameters included biochemistry, hematology, and urinalysis.	From first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
Primary	Number of Participants With a Change in Urine Output Reported as an Adverse Event	Urine and stool output was 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 first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
Primary	Number of Participants With a Change in Stool Output Reported as an Adverse Event	Urine and stool output was 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 first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
Secondary	Change From Baseline in PS Volume	PS (parenteral nutrition or intravenous fluids) was considered for managing nutritional support in terms of volume and calories during the treatment period. An end of treatment (EOT) was defined as the last determination of endpoint of the last cycle.	Baseline, Cycle 1 = Week 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 2: Week 0, 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 3 = Week 0, 1, 2, and EOT and overall EOT (for up to 47.3-51.3 weeks) [cycle length=28 weeks]
Secondary	Percent Change From Baseline in PS Volume	Percent change from baseline in PS volume was calculated as follows; (PS volume at each point [Week 1, 2, 4, 8, 12, 16, 20, 24, and EOT] - PS volume at baseline)/ PS volume at baseline *100 (percent). PS (parenteral nutrition or intravenous fluids) was to be considered for managing nutritional support in terms of volume and calories during the treatment period. An EOT was defined as the last determination of endpoint of the last cycle.	Baseline, Cycle 1 = Week 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 2 = Week 0, 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 3 = Week 0, 1, 2, and EOT and overall EOT (for up to 47.3-51.3 weeks) [cycle length=28 weeks]
Secondary	Number of Participants Who Demonstrate at Least 20 Percent (%) Reduction From Baseline in PS Volume	PS (parenteral nutrition or intravenous fluids) was considered for managing nutritional support in terms of volume and calories during the treatment period. An EOT was defined as the last determination of endpoint of the last cycle.	Baseline, Cycle 1 = Week 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 2 = Week 0, 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 3 = Week 0, 1, 2, and EOT and overall EOT (for up to 47.3-51.3 weeks) [cycle length=28 weeks]
Secondary	Number of Participants Who Achieved Enteral Autonomy	Achieving enteral autonomy is defined as complete weaning off PS. PS (parenteral nutrition or intravenous fluids) was to be considered for managing nutritional support in terms of volume and calories during the treatment period.	Cycle 1 = Week 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 2 = Week 0, 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 3 = Week 0, 1, 2, and EOT and overall EOT (for up to 47.3-51.3 weeks) [cycle length=28 weeks]
Secondary	Change From Baseline in Number of Days Per Week of PS Usage at EOT	PS (parenteral nutrition or intravenous fluids) was considered for managing nutritional support in terms of volume and calories during the treatment period.	Baseline, Cycle 1 = Week 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 2 = Week 0, 1, 2, 4, 8, 12, 16, 20, 24, and EOT, Cycle 3 = Week 0, 1, 2, and EOT, and overall EOT (for 47.3-51.3 weeks) [cycle length=28 weeks]

External Links

•   To obtain more information on the study, click here/on this link.