Clinical Trial Results:
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
Summary
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EudraCT number |
2017-003606-40 |
Trial protocol |
GB FI IT FR |
Global end of trial date |
24 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Mar 2021
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First version publication date |
28 Mar 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SHP633-301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03571516 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Shire
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Sponsor organisation address |
300 ShireWay, Lexington, United States, MA 02421
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Public contact |
Study Director, Shire, +1 866 842 5335, ClinicalTransparency@shire.com
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Scientific contact |
Study Director, Shire, +1 866 842 5335, ClinicalTransparency@shire.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000482-PIP01-08 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Sep 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Sep 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to evaluate the safety, efficacy/pharmacodynamics(PD) and pharmacokinetics (PK) of teduglutide treatment in infants with short bowel syndrome (SBS) dependent on parenteral support.
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Protection of trial subjects |
The study was conducted in accordance with the ethical principles that have their origins in the
Declaration of Helsinki and in compliance with all applicable industry regulations, International
Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996),
European Union (EU) Directive 2001/20/EC, as well as all applicable national and local laws
and regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Aug 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Finland: 2
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Country: Number of subjects enrolled |
United Kingdom: 8
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Worldwide total number of subjects |
10
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
10
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at Finland and United Kingdom between 31 August 2018 (first subject first visit) and 24 September 2020 (last subject last visit). | ||||||||||||||||||
Pre-assignment
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Screening details |
A total of 10 subjects were enrolled into the study, of which 8 subjects completed the study. | ||||||||||||||||||
Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Teduglutide (TED) | ||||||||||||||||||
Arm description |
Subjects (infants) 4 to 12 months of corrected gestational aged received 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injection once daily (QD) in addition to standard medical therapy for 24 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Revestive
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Investigational medicinal product code |
A16AX08
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects (infants) received 0.05 mg/kg of teduglutide SC injection into abdomen or into either the thigh or arm.
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Arm title
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Standard of Care (SOC) | ||||||||||||||||||
Arm description |
Subjects (infants) 4 to 12 months of corrected gestational aged received standard medical therapy for 24 weeks. | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Teduglutide (TED)
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Reporting group description |
Subjects (infants) 4 to 12 months of corrected gestational aged received 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injection once daily (QD) in addition to standard medical therapy for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard of Care (SOC)
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Reporting group description |
Subjects (infants) 4 to 12 months of corrected gestational aged received standard medical therapy for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Teduglutide (TED)
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Reporting group description |
Subjects (infants) 4 to 12 months of corrected gestational aged received 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injection once daily (QD) in addition to standard medical therapy for 24 weeks. | ||
Reporting group title |
Standard of Care (SOC)
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Reporting group description |
Subjects (infants) 4 to 12 months of corrected gestational aged received standard medical therapy for 24 weeks. |
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End point title |
Number of Subjects Who Achieved At least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) [1] | |||||||||||||||
End point description |
Number of subjects who achieved at least 20% reduction from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. Intent-to-Treat (ITT) set consisted of all subjects randomized in the study.
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End point type |
Primary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical and comparision analysis were performed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7) [2] | ||||||||||||||||
End point description |
Mean plasma concentration of teduglutide at nominal time points was reported. Pharmacokinetic (PK) set included all subjects who received at least one dose of teduglutide and have at least one evaluable and interpretable post-dose PK concentration value. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint and n=number of subjects analysed refer to the subjects evaluable for this specific time points. Data was not planned to be collected and analysed for SOC arm.
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End point type |
Secondary
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End point timeframe |
Baseline: Pre-dose, 1, 4 hours post-dose, and 2 hours post-dose on Week 7
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Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was only planned to be analysed for the reporting group of “Teduglutide” arm. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | |||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject 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. Safety set consisted of all subjects who met the following criteria: Teduglutide treatment arm: subjects who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: subjects who had undergone at least 1 post baseline safety assessment.
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End point type |
Secondary
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End point timeframe |
From start of study treatment up to end of study (EOS) (up to Week 28)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Body Weight Z-score at Week 24 | ||||||||||||
End point description |
Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in body weight Z-score at Week 24 was reported. Safety set consisted of all subjects who met the following criteria: Teduglutide treatment arm: subjects who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: subjects who had undergone at least 1 post baseline safety assessment. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Length Z-Score at Week 24 | ||||||||||||
End point description |
Length was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in length Z-score at Week 24 was reported. Safety set consisted of all subjects who met the following criteria: Teduglutide treatment arm: subjects who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: subjects who had undergone at least 1 post baseline safety assessment. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Head Circumference Z-Score at Week 24 | ||||||||||||
End point description |
Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in head circumference Z-score at Week 24 was reported. Safety set consisted of all subjects who met the following criteria: Teduglutide treatment arm: subjects who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: subjects who had undergone at least 1 post baseline safety assessment. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Weight-for-Length Z-Score at Week 24 | ||||||||||||
End point description |
Weight-for-length was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in weight-for-length Z-score at Week 24 was reported. Safety set consisted of all subjects who met the following criteria: Teduglutide treatment arm: subjects who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: subjects who had undergone at least 1 post baseline safety assessment. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Average Total Urine Output at Week 24 | ||||||||||||
End point description |
Average total urine output was recorded over a 48-hour period of nutritional stability at Week 24 was reported. Safety set consisted of all subjects who met the following criteria: Teduglutide treatment arm: subjects who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: subjects who had undergone at least 1 post baseline safety assessment. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint. Here, milliliter per kilogram per day is abbreviated as mL/kg/day.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Fecal Output at Week 24 | ||||||||||||
End point description |
Change from baseline in the fecal output (Average number of stools per day) at Week 24 was reported. Safety set consisted of all subjects who met the following criteria: Teduglutide treatment arm: subjects who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: subjects who had undergone at least 1 post baseline safety assessment. Here, the number of subjects analysed refer to the subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Positive Specific Antibodies to Teduglutide [3] | ||||||
End point description |
Number of subjects with positive specific antibodies to teduglutide were used to summarize the presence of antibodies. Safety set consisted of all subjects who met the following criteria: Teduglutide treatment arm: subjects who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: subjects who had undergone at least 1 post baseline safety assessment. Here, the number of subjects analysed signifies subjects who were evaluable for this endpoint. Data for this endpoint was not planned to be collected and analyzed for SOC group.
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End point type |
Secondary
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End point timeframe |
Baseline, EOS (up to week 28)
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Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint was only planned to be analysed for the reporting group of “Teduglutide” arm. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects Who Achieved At least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | |||||||||||||||
End point description |
Number of subjects who achieved at least 20% reduction from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Number of Subjects Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at Week 24 | |||||||||
End point description |
Number of subjects who achieved 100% reduction in complete weaning off (enteral autonomy) PS volume at Week 24 were reported. ITT set consisted of all subjects randomized in the study. Here, the number of subjects analysed signifies subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Week 24
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No statistical analyses for this end point |
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End point title |
Number of Subjects Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at End of Study (EOS) | |||||||||
End point description |
Number of subjects who achieved 100% reduction in complete weaning off (enteral autonomy) PS volume at EOS (up to Week 28) were reported. ITT set consisted of all subjects randomized in the study. Here, the number of subjects analysed signifies subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
EOS (up to Week 28)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | ||||||||||||||||||
End point description |
Change from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study. Here, n=number of subjects analysed refer to the subjects evaluable for this specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | ||||||||||||||||||
End point description |
Percent change from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study. Here, n=number of subjects analysed refer to the subjects evaluable for this specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | ||||||||||||||||||
End point description |
Change from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day). ITT set consisted of all subjects randomized in the study. Here, n=number of subjects analysed refer to the subjects evaluable for this specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | ||||||||||||||||||
End point description |
Percent change from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study. Here, n=number of subjects analysed refer to the subjects evaluable for this specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | ||||||||||||||||||
End point description |
Change from baseline in weight-normalized EN volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study. Here, n=number of subjects analysed refer to the subjects evaluable for this specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) volume at End of Treatment/Early Termination (EOT/ET) | ||||||||||||||||||
End point description |
Percent change from baseline in weight-normalized EN volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study. Here, '99999' indicates that standard deviation was not analysed for this category as there were only one subjects available at specified time points. Here, n=number of subjects analysed refer to the subjects evaluable for this specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | ||||||||||||||||||
End point description |
Change from baseline in weight-normalized EN caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study. Here, n=number of subjects analysed refer to the subjects evaluable for this specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | ||||||||||||||||||
End point description |
Percent change from baseline in weight-normalized EN caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study. Here, '99999' indicates that standard deviation was not analysed for this category as there were only one subjects available at specified time points. Here, n=number of subjects analysed refer to the subjects evaluable for this specific time points.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Number of Subjects Who Achieved At least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | |||||||||||||||
End point description |
Number of subjects who achieved at least 20% increase from baseline in weight-normalized EN volume at EOT/ET was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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End point title |
Number of Subjects Who Achieved At least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | |||||||||||||||
End point description |
Number of subjects who achieved at least 20% increase from baseline in weight-normalized EN caloric intake at EOT/ET was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. ITT set consisted of all subjects randomized in the study.
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End point type |
Secondary
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End point timeframe |
Baseline, EOT/ET (up to Week 24)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From start of study treatment up to end of study (EOS) (up to Week 28)
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
Teduglutide
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Reporting group description |
Subjects (infants) 4 to 12 months of corrected gestational aged received 0.05 mg/kg of teduglutide SC injection once daily for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard of Care (SOC)
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Reporting group description |
Subjects (infants) 4 to 12 months of corrected gestational aged received standard medical therapy for 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Jan 2018 |
Protocol Amendment 1:
- Clarification that subjects must have been 4 to 12 months corrected gestational age at screening.
- Pharmacokinetic sampling on Week 6 was moved to Week 7 so that samples could be collected without exceeding the weekly/monthly total blood volume restrictions. Clarification that blood for post-dose PK samples might be taken within ±10 minutes of the time pre-specified.
- Teduglutide dose adjustments were changed to Week 12 rather than at every clinic visit to reduce the site burden.
- Assessment of the 5-level EuroQol five dimensions questionnaire was removed to reduce the caregiver burden. |
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04 Dec 2018 |
Protocol Amendment 2:
- The dose selection rationale was updated with results from a simulation work using the previous population PK model. Based on the totality of clinical data, 0.05 mg/kg once daily was expected to provide comparable Cmax concentrations in infants as compared to pediatric subjects with SBS and was recommended as an evaluation dosing regimen in Study SHP633-301. |
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24 May 2019 |
Amendment 3:
- The significant change in this amendment included the deletion of inclusion criterion 6: “Lack of terminal ileum and ileocecal valve.” due to difficulties in enrollment. |
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17 Dec 2019 |
Protocol Amendment 4: - Specification that the pre-dose PK sample was not to be collected from subjects who weighed lesser than (<) 7 kilograms (kg). The optional PK measurement at Week 12 was removed; postbaseline PK samples were to be performed at Week 7. The information to be collected for PK assessments was clarified. - Clarification that subjects might enroll in an extension study at EOS if that study was open to enrollment at the time of the SHP633-301 EOS. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |