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Safety, Efficacy and Pharmacokinetic Study of Teduglutide in Infants 4 to 12 Months of Age With Short Bowel Syndrome

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ClinicalTrials.gov Identifier: NCT03571516
Recruitment Status : Recruiting
First Posted : June 27, 2018
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
The purpose of the study is to evaluate the safety, efficacy/pharmacodynamics (PD) and pharmacokinetics (PK) of teduglutide treatment in infants with short bowel syndrome (SBS) dependent on parenteral (PN) support.

Condition or disease Intervention/treatment Phase
Short Bowel Syndrome Drug: Teduglutide Other: Standard Medical Therapy Device: Syringe Device: Needle Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, 24-Week Safety, Efficacy, and Pharmacokinetic Study of Teduglutide in Infants 4 to 12 Months of Age With Short Bowel Syndrome Who Are Dependent on Parenteral Support
Actual Study Start Date : August 6, 2018
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Teduglutide

Arm Intervention/treatment
Experimental: Teduglutide
Participants will receive 0.05 milligram per kilogram (mg/kg) subcutaneous (SC) injection of teduglutide into abdomen or into either the thigh or arm once daily (QD) in addition to standard medical therapy for 24 weeks.
Drug: Teduglutide
SC injection of 0.05 mg/kg teduglutide will be administered QD into abdomen or into either the thigh or arm for 24 weeks.

Other: Standard Medical Therapy
Standard medical therapy will be administered for 24 weeks.

Device: Syringe
Teduglutide will be administered using syringe (510k number: K980987).

Device: Needle
Teduglutide will be administered using needle (510k number: K021475).

Standard of Care (SOC)
Participants will receive standard medical therapy for 24 weeks.
Other: Standard Medical Therapy
Standard medical therapy will be administered for 24 weeks.

Device: Syringe
Teduglutide will be administered using syringe (510k number: K980987).

Device: Needle
Teduglutide will be administered using needle (510k number: K021475).




Primary Outcome Measures :
  1. Number of Participants who Achieve At least a 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Nutrition (PN) Fluid Volume at Week 24 [ Time Frame: From baseline up to Week 24 ]
    Number of participants who achieve at least a 20% reduction from baseline in weight-normalized average daily PN volume at Week 24/ end of treatment (EOT) will be summarized by treatment arm.

  2. Plasma Concentration of Teduglutide [ Time Frame: Pre-dose; 1, 4 hours post-dose, and 2 hours post-dose on Week 7 or 12 ]
    Plasma Concentration as a Pharmacokinetic parameter of Teduglutide will be assessed. The estimation will be calculated by using a population PK modeling approach.

  3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From start of study treatment up to Week 28 (Follow-up) ]
    An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs that start or deteriorate on or after the date of the first dose of investigational product.

  4. Change From Baseline in Body Weight Z-Score [ Time Frame: Baseline, Week 1,Week 3, Week 5, Week 7, Week 9, Week 12, Week 16, Week 20, Week 24 and Week 28 ]
    The Z-score indicates the number of standard deviations away from the mean.

  5. Change From Baseline in Length Z-Score [ Time Frame: Baseline, Week 5, Week 12, Week 16, Week 20, Week 24 and Week 28 ]
    The Z-score indicates the number of standard deviations away from the mean.

  6. Change From Baseline in Head Circumference Z-Score [ Time Frame: Baseline, Week 5, Week 12, Week 16, Week 20, Week 24 and Week 28 ]
    The Z-score indicates the number of standard deviations away from the mean.

  7. Change From Baseline in Weight-for-Length Z-Score [ Time Frame: Baseline, Week 5, Week 12, Week 16, Week 20, Week 24 and Week 28 ]
    The Z-score indicates the number of standard deviations away from the mean.

  8. Change From Baseline in Urine Output [ Time Frame: Baseline, Week 1, Week 3, Week 5, Week 7, Week 9, Week 12, Week 16, Week 20, Week 24 ]
    Urine output will be recorded in the output diary over a 48-hour period of nutritional stability before every clinic visit, and within 1 week of implementing a change in the PN prescription.

  9. Change From Baseline in Stool Output [ Time Frame: Baseline, Week 1, Week 3, Week 5, Week 7, Week 9, Week 12, Week 16, Week 20, Week 24 ]
    Stool output will be recorded in the output diary over a 48-hour period of nutritional stability before every clinic visit, and within 1 week of implementing a change in the PN prescription.

  10. Antibodies to Teduglutide [ Time Frame: Baseline, Week 12 and Week 28 ]
    Number of participants classified as having positive specific antibodies to teduglutide will be used to summarize the presence of antibodies.


Secondary Outcome Measures :
  1. Number of Participants who Achieve At least a 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral (PN) Calories at Week 24 [ Time Frame: Week 24 ]
    Number of participants who achieve at least a 20% reduction from baseline in weight-normalized parenteral calories at Week 24/EOT will be summarized by treatment arm.

  2. Enteral Autonomy at Week 24 [ Time Frame: Week 24 ]
    Number of participants who have achieved enteral autonomy at a given visit if the investigator prescribes no PS at that visit and there is no use of PN recorded in the participant diary during the week prior to that visit.

  3. Time to Achieve Enteral Autonomy [ Time Frame: From baseline up to Week 28 ]
    A participant will be considered to have achieved enteral autonomy (completely weaned off PN) if the investigator prescribes no PN and for the remainder of the treatment period.

  4. Change From Baseline in Weight-normalized Parenteral nutrition (PN) Fluid Volume [ Time Frame: Baseline, Week 1, Week 3, Week 5, Week 7, Week 9, Week 12, Week 16, Week 20 and Week 24 ]
    Change from baseline in weight-normalized PN fluid volume will be analyzed.

  5. Change From Baseline in Weight-normalized Parenteral Calories [ Time Frame: Baseline, Week 1, Week 3, Week 5, Week 7, Week 9, Week 12, Week 16, Week 20 and Week 24 ]
    Change from baseline in weight-normalized parenteral calories will be analyzed.

  6. Change From Baseline in Weight-normalized Enteral Fluid Volume [ Time Frame: Baseline, Week 1, Week 3, Week 5, Week 7, Week 9, Week 12, Week 16, Week 20 and Week 24 ]
    Change from baseline in weight-normalized enteral fluid volume will be analyzed.

  7. Change From Baseline in Weight-normalized Enteral Caloric Intake [ Time Frame: Baseline, Week 1, Week 3, Week 5, Week 7, Week 9, Week 12, Week 16, Week 20 and Week 24 ]
    Change from baseline in weight-normalized enteral caloric intake will be analyzed.

  8. Number of Participants who Achieve At least a 20 Percent (%) Increase From Baseline in Weight-normalized Enteral (EN) Fluid Intake at Week 24 [ Time Frame: From baseline up to Week 24 ]
    Number of participants who demonstrate an increase in weight-normalized enteral fluid intake by at least 20% from baseline to Week 24/EOT will be summarized by treatment arm.

  9. Number of Participants who Acheive At least a 20 Percent (%) Increase From Baseline in Weight-normalized Enteral (EN) Caloric Intake at Week 24 [ Time Frame: From baseline up to Week 24 ]
    Number of participants who demonstrate an increase in weight-normalized enteral caloric intake by at least 20% from baseline to week 24/EOT will be summarized by treatment arm.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   4 Months to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Informed consent by the parent or legal guardian.
  • Male or female infant 4 to 12 months corrected gestational age at screening.
  • Weight at least 5 kilogram (kg) and weight-for-length Z-score greater than -2 at screening and baseline.
  • Short bowel syndrome with dependence on parenteral support to provide at least 50% of fluid or caloric needs.
  • Stable PN requirements for at least 1 month prior to screening, defined as a less than or equal to (<=) 10% change in the weight-normalized PN total fluid and caloric intake, despite attempts to wean PN, not withstanding transient instability for events such as sepsis or interruption of central venous access.
  • Lack of terminal ileum and ileocecal valve.
  • Parent or legal guardian understands and is willing and able to fully adhere to study requirements as defined in this protocol.

Exclusion Criteria:

  • Previous treatment with teduglutide.
  • 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 PN support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding.
  • Inability to advance oral or enteral feeding due to lack of access to the gut, such as oral aversion in the absence of a feeding tube.
  • Intestinal obstruction or clinically significant intestinal stenosis.
  • Major gastrointestinal surgical intervention, such as serial transverse enteroplasty or major intestinal resection or anastomosis, within 3 months prior to screening or planned during the study period.
  • Unstable cardiac disease.
  • Renal dysfunction, defined as estimated glomerular filtration rate less than (<) 50 milliliter per minute (mL/min) per 1.73 square meter (m^2).
  • Biliary obstruction, stenosis, or malformation.
  • Clinically significant pancreatic disease.
  • Severe hepatic dysfunction or portal hypertension, defined by at least 2 of the following parameters:

    1. International normalized ratio (INR) greater than (>) 1.5 not corrected with PN vitamin K
    2. Platelet count <100×10^3/ microliter (mcL) due to portal hypertension
    3. Presence of clinically significant gastric or esophageal varices
    4. Documented cirrhosis
  • Persistent cholestasis defined as conjugated bilirubin >4 milligram per deciliter (mg/dL) (>68 micromoles per liter [mcmol/L]) over a 2 week period.
  • More than 3 serious complications of intestinal failure (example [e.g.], catheter-associated bloodstream infections, interruption of nutrition due to feeding intolerance, catheter-associated thrombosis, severe fluid or electrolyte disturbances) within 1 month prior to or during screening.
  • A history of cancer or a known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of gastrointestinal cancer (including hepatobiliary and pancreatic cancers).
  • Concurrent treatment with glucagon-like peptide-1 (GLP-1); glucagon-like peptide-2 (GLP-2); insulin-like growth factor-1 (IGF-1); growth hormone, somatostatin, or analogs of these hormones; or glutamine.
  • Participation in a clinical study using an experimental drug within 3 months or 5.5 half-lives of the experimental drug, whichever is longer.
  • Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients.
  • Any condition, disease, illness, or circumstance that, in the investigator's opinion, puts the participant at any undue risk, prevents completion of the study, or interferes with analysis of the study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03571516


Contacts
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Contact: Shire Contact 1 866-842-5335 ClinicalTransparency@shire.com

Locations
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Finland
Helsingin yliopistollinen keskussairaala Recruiting
Helsinki, Finland, 00290
Contact: Site Contact    +358504272981    mikko.pakarinen@hus.fi   
Principal Investigator: Mikko Pakarinen, Dr.         
France
Groupe Hospitalier Pellegrin - Hôpital des Enfants Recruiting
Bordeaux, Gironde, France, 33000
Contact: Site Contact    +33556799824    thierry.lamireau@chu-bordeaux.fr   
Principal Investigator: Thierry Lamireau, Prof.         
Hopital Jeanne de Flandre - CHRU Lille Recruiting
Lille, Nord, France, 59037
Contact: Site Contact    +33320446126    frederic.gottrand@chru-lille.fr   
Principal Investigator: Frederic Gottrand, Prof.         
United Kingdom
Great Ormond Street Hospital for Children Recruiting
London, Greater London, United Kingdom, WC1N 3JH
Contact: Site contact    +441512284811    susan.hill@gosh.nhs.uk   
Principal Investigator: Susan Hill, Dr.         
Royal Manchester Children's Hospital Recruiting
Manchester, Greater Manchester, United Kingdom, M13 9WL
Contact: Site Contact    +441617012371    andrew.fagbemi@cmft.nhs.uk   
Principal Investigator: Andrew Fagbemi, Dr.         
Alder Hey Childrens Hospital Recruiting
Liverpool, Merseyside, United Kingdom, L12 2AP
Contact: Site Contact    +441512284811    anastasia.konidari@alderhey.nhs.uk   
Principal Investigator: Anastasia Konidari, Dr.         
Birmingham Children's Hospital Recruiting
Birmingham, West Midlands, United Kingdom, B4 6NH
Contact: Site Contact    +441213338705    sue.protheroe@bch.nhs.uk   
Principal Investigator: Susan Protheroe, Dr.         
Sponsors and Collaborators
Shire
Investigators
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Study Director: Study Director Shire

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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03571516     History of Changes
Other Study ID Numbers: SHP633-301
2017-003606-40 ( EudraCT Number )
First Posted: June 27, 2018    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites, …).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Shire:
Short bowel syndrome
Teduglutide

Additional relevant MeSH terms:
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Syndrome
Short Bowel Syndrome
Disease
Pathologic Processes
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Postoperative Complications
Teduglutide
Gastrointestinal Agents
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs