Clinical trial NCT05027308: A Study of Teduglutide in Japanese Children With Short Bowel Syndrome Aged 4 Months or Older
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Short Bowel Syndrome
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-08-30
Enrollment: 3
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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})
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: From first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as an Adverse Event
timeFrame: From first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
measure: Change From Baseline in Body Weight Z-Score at EOT
timeFrame: Baseline, EOT (up to 47.3-51.3 weeks)
measure: Change From Baseline in Height Z-Score at EOT
timeFrame: Baseline, EOT (up to 47.3-51.3 weeks)
measure: Change From Baseline in Head Circumference Z-Score at EOT
timeFrame: Baseline, EOT (up to 47.3-51.3 weeks)
measure: Change From Baseline in Weight-for-Length Z-Score at EOT
timeFrame: Baseline, EOT (up to 47.3-51.3 weeks)
measure: Number of Participants With Any Laboratory Safety Finding Reported as an Adverse Event
timeFrame: From first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
measure: Number of Participants With a Change in Urine Output Reported as an Adverse Event
timeFrame: From first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
measure: Number of Participants With a Change in Stool Output Reported as an Adverse Event
timeFrame: From first dose of study drug until follow-up visit (4 weeks after EOT/ET [up to 47.3-51.3 weeks])
Secondary outcomes:
measure: Change From Baseline in PS Volume
timeFrame: 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]
measure: Percent Change From Baseline in PS Volume
timeFrame: 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]
measure: Number of Participants Who Demonstrate at Least 20 Percent (%) Reduction From Baseline in PS Volume
timeFrame: 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]
measure: Number of Participants Who Achieved Enteral Autonomy
timeFrame: 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]
measure: Change From Baseline in Number of Days Per Week of PS Usage at EOT
timeFrame: 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]
Other outcomes:
Locations:
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Shinagawa-ku
country: Japan
facility: Showa University Hospital
state: Tokyo
city: Akita
country: Japan
facility: Akita University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Kagoshima
country: Japan
facility: Kagoshiha University Hospital
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: