Characterization of the Long-term Safety, Efficacy, and Pharmacodynamics Revestive® in the Management of Short Bowel Syndrome Pediatric Patients (REVE)
Primary Purpose
Short Bowel Syndrome
Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Teduglutide
Sponsored by
About this trial
This is an interventional treatment trial for Short Bowel Syndrome focused on measuring Teduglutide, Short Bowel Syndrome, Parenteral nutrition, Intestinal failure
Eligibility Criteria
Inclusion Criteria:
- Being aged from 2 to 18 years old included ;
- Presenting less than 80 cm of residual small intestine with or without the terminal ileum, ileocecal valve and right colon or having less than 120 cm in case of Short Bowel Syndrome (SBS) caused by Hirschsprung disease;
- Being stable on PN support (inability to significantly reduce PN intake for the last six months before inclusion) ;
- Being dependent on PN for at least 2 years and enterally fed (oral or tube feeding) ;
- Having a normal colonoscopy in the 12 months before screening for children with maintained colon (=SBS type 2 or 3) older than 12 years ;
- Having signed the Informed consent form (or parents or legal representative for minor patients).
Exclusion Criteria:
- Having a major gastrointestinal surgical intervention like serial transverse enteroplasty or any other bowel lengthening procedure performed within 6 months of screening ;
- Having a clinically significant untreated intestinal obstruction or active stenosis ;
- Having an unstable absorption due to cystic fibrosis or known DNA abnormalities ;
- Presenting a radiographic or manometric evidence of pseudo-obstruction or severe known dysmotility syndrome, including persistent, severe gastroschisis-related motility disorders ;
- Having an unstable cardiac disease, congenital heart disease or cyanotic disease, with the exception of patients who had undergone ventricular or atrial septal defect repair ;
- Having a history of cancer or clinically significant lymphoproliferative disease; excepted resected cutaneous basal or squamous cell carcinoma, or in situ non-aggressive and surgically resected cancer ;
- Having participated in a clinical study using an experimental drug within 1 month or an experimental antibody treatment within 3 months prior to screening, or concurrent participation in any clinical study using an experimental drug that would affect the safety of teduglutide ;
- Having already used native GLP-2 and glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening ;
- Having already used oral or IV glutamine, octreotide, or dipeptidyl peptidase IV (DPP-IV) inhibitors within 3 months prior to screening ;
- Having an active Crohn's disease which has been treated with biological therapy within the 6 months prior to screening ;
- Having an intestinal polyposis;
- Being, for female patient, both lactating and breast-feeding or having a positive pregnancy test during the screening period;
- Refusing the follow the protocol requirements in terms of birth control ;
- Being unable to follow the study procedures for any reason: psychological, geographical…
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of Summary of Product Characteristics (SPC), or trace residues of tetracycline.
- Active or suspected malignancy.
- Patients with a history of malignancies in the gastrointestinal tract including the hepatobiliary system within the last five years.
Sites / Locations
- Hôpital Necker - Enfants malades
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Revestive
Arm Description
Revestive® (teduglutide)is administered in children sub cutaneous injection at 0.05 mg/kg body weight once daily
Outcomes
Primary Outcome Measures
Decrease in parenteral nutrition: Parenteral Nutrition/Resting Energy Expenditure (PN/REE)
Evaluate the efficacy of Revestive® treatment
Secondary Outcome Measures
Ostomy output defined as stool balance testing, urine output and plasma citrulline
Evaluate the impact of Revestive on ostomy flow
Change in days per week of Parenteral Nutrition (PN)
Quantify the impact of Revestive on the number of perfusion in a week
Change in number of stool per day
to evaluate the impact of Revestive on diarrhea
Change in stools consistency (Bristol stool chart)
to evaluate the impact of Revestive on diarrhea
Ingesta (calorimetric measure)
to evaluate the impact of Revestive on Intestinal absorption
Stool weight/24h
to evaluate the impact of Revestive on Intestinal absorption
Percentage of lipid in stool
to evaluate the impact of Revestive on Intestinal absorption
Percentage of nitrogen in stool
to evaluate the impact of Revestive on Intestinal absorption
Percentage of carbohydrate in stool
to evaluate the impact of Revestive on Intestinal absorption
Percentage of sodium in stool
to evaluate the impact of Revestive on Intestinal absorption
Number of adverse events
to evaluate the long term safety of Revestive
Change in body weight
Change in heart rate
Change in blood pressure
Endogenous GLP-2 rates (antibody ELISA)
to evaluate the response rate of Revestive
Full Information
NCT ID
NCT03562130
First Posted
May 18, 2018
Last Updated
December 3, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Imagine Institute
1. Study Identification
Unique Protocol Identification Number
NCT03562130
Brief Title
Characterization of the Long-term Safety, Efficacy, and Pharmacodynamics Revestive® in the Management of Short Bowel Syndrome Pediatric Patients
Acronym
REVE
Official Title
A Monocentric Single-arm Study to Characterize the Long-term Safety, Efficacy, and Pharmacodynamic of GLP-2 Analog (Revestive®) in the Management of Short Bowel Syndrome Pediatric Patients on Home-parenteral Nutrition (HPN)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
July 2, 2018 (Actual)
Primary Completion Date
December 11, 2019 (Actual)
Study Completion Date
July 13, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Imagine Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate if the treatment could maximize intestinal absorption, minimize the inconvenience of diarrhea, and avoid, reduce or eliminate the need for parenteral support (PS) to achieve normal growth, to avoid parenteral nutrition complications and to achieve the best possible quality of life for the patient
Detailed Description
The short bowel syndrome (SBS) may be defined as a severe malabsorption caused by reduction of intestinal absorptive surface following massive resection of the small intestine. Teduglutide (Revestive®) is an analog of glucagon-like peptide 2 (GLP-2), a naturally occurring hormone that regulates the functional and structural integrity of the cells lining the gastrointestinal tract. The aim of the treatment is to maximize intestinal absorption, minimize the inconvenience of diarrhea, and avoid, reduce or eliminate the need for parenteral support (PS) to achieve the best possible quality of life for the patient. The rationale for the use of Revestive® is based on data obtained, especially in the trial in SBS patients.
Treatment with 0.05 mg/kg/day was safe and well tolerated (no recorded side effects).
Patients remained stable despite substantial reduction in parenteral nutrition (PN) supply as evidenced by stable body weight and height, serum electrolytes, pancreatic enzymes and renal function tests.
Treatment was associated with:
Reduced PN volume and calories delivered by 25 and 45% respectively with 20% of patients weaned off PN during the study period
Increased Enteral Nutrition (EN) supply in volume and calories by 40 and 62% respectively
Increased in plasma citrulline during the treatment period, but decreased after Teduglutide discontinuation The recommended dose of Revestive® in children and adolescents (aged 1 to 17 years) is the same as for adults (0.05 mg/kg body weight once daily).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Short Bowel Syndrome
Keywords
Teduglutide, Short Bowel Syndrome, Parenteral nutrition, Intestinal failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Revestive
Arm Type
Experimental
Arm Description
Revestive® (teduglutide)is administered in children sub cutaneous injection at 0.05 mg/kg body weight once daily
Intervention Type
Drug
Intervention Name(s)
Teduglutide
Intervention Description
Daily sub cutaneous injection 0,05 mg/kg/day
Primary Outcome Measure Information:
Title
Decrease in parenteral nutrition: Parenteral Nutrition/Resting Energy Expenditure (PN/REE)
Description
Evaluate the efficacy of Revestive® treatment
Time Frame
At week 24
Secondary Outcome Measure Information:
Title
Ostomy output defined as stool balance testing, urine output and plasma citrulline
Description
Evaluate the impact of Revestive on ostomy flow
Time Frame
up to week 48
Title
Change in days per week of Parenteral Nutrition (PN)
Description
Quantify the impact of Revestive on the number of perfusion in a week
Time Frame
up to week 48
Title
Change in number of stool per day
Description
to evaluate the impact of Revestive on diarrhea
Time Frame
up to week 48
Title
Change in stools consistency (Bristol stool chart)
Description
to evaluate the impact of Revestive on diarrhea
Time Frame
up to week 48
Title
Ingesta (calorimetric measure)
Description
to evaluate the impact of Revestive on Intestinal absorption
Time Frame
Every 4 weeks up to week 48
Title
Stool weight/24h
Description
to evaluate the impact of Revestive on Intestinal absorption
Time Frame
Every 4 weeks up to week 48
Title
Percentage of lipid in stool
Description
to evaluate the impact of Revestive on Intestinal absorption
Time Frame
Every 4 weeks up to week 48
Title
Percentage of nitrogen in stool
Description
to evaluate the impact of Revestive on Intestinal absorption
Time Frame
Every 4 weeks up to week 48
Title
Percentage of carbohydrate in stool
Description
to evaluate the impact of Revestive on Intestinal absorption
Time Frame
Every 4 weeks up to week 48
Title
Percentage of sodium in stool
Description
to evaluate the impact of Revestive on Intestinal absorption
Time Frame
Every 4 weeks up to week 48
Title
Number of adverse events
Description
to evaluate the long term safety of Revestive
Time Frame
At week 48
Title
Change in body weight
Time Frame
At baseline, then at 6 and 12 months
Title
Change in heart rate
Time Frame
At baseline, then at 6 and 12 months
Title
Change in blood pressure
Time Frame
At baseline, then at 6 and 12 months
Title
Endogenous GLP-2 rates (antibody ELISA)
Description
to evaluate the response rate of Revestive
Time Frame
up to week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Being aged from 2 to 18 years old included ;
Presenting less than 80 cm of residual small intestine with or without the terminal ileum, ileocecal valve and right colon or having less than 120 cm in case of Short Bowel Syndrome (SBS) caused by Hirschsprung disease;
Being stable on PN support (inability to significantly reduce PN intake for the last six months before inclusion) ;
Being dependent on PN for at least 2 years and enterally fed (oral or tube feeding) ;
Having a normal colonoscopy in the 12 months before screening for children with maintained colon (=SBS type 2 or 3) older than 12 years ;
Having signed the Informed consent form (or parents or legal representative for minor patients).
Exclusion Criteria:
Having a major gastrointestinal surgical intervention like serial transverse enteroplasty or any other bowel lengthening procedure performed within 6 months of screening ;
Having a clinically significant untreated intestinal obstruction or active stenosis ;
Having an unstable absorption due to cystic fibrosis or known DNA abnormalities ;
Presenting a radiographic or manometric evidence of pseudo-obstruction or severe known dysmotility syndrome, including persistent, severe gastroschisis-related motility disorders ;
Having an unstable cardiac disease, congenital heart disease or cyanotic disease, with the exception of patients who had undergone ventricular or atrial septal defect repair ;
Having a history of cancer or clinically significant lymphoproliferative disease; excepted resected cutaneous basal or squamous cell carcinoma, or in situ non-aggressive and surgically resected cancer ;
Having participated in a clinical study using an experimental drug within 1 month or an experimental antibody treatment within 3 months prior to screening, or concurrent participation in any clinical study using an experimental drug that would affect the safety of teduglutide ;
Having already used native GLP-2 and glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening ;
Having already used oral or IV glutamine, octreotide, or dipeptidyl peptidase IV (DPP-IV) inhibitors within 3 months prior to screening ;
Having an active Crohn's disease which has been treated with biological therapy within the 6 months prior to screening ;
Having an intestinal polyposis;
Being, for female patient, both lactating and breast-feeding or having a positive pregnancy test during the screening period;
Refusing the follow the protocol requirements in terms of birth control ;
Being unable to follow the study procedures for any reason: psychological, geographical…
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of Summary of Product Characteristics (SPC), or trace residues of tetracycline.
Active or suspected malignancy.
Patients with a history of malignancies in the gastrointestinal tract including the hepatobiliary system within the last five years.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier GOULET, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Necker - Enfants malades
City
Paris
ZIP/Postal Code
75015
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Characterization of the Long-term Safety, Efficacy, and Pharmacodynamics Revestive® in the Management of Short Bowel Syndrome Pediatric Patients
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