Characterization of the Long-term Safety, Efficacy, and Pharmacodynamics Revestive® in the Management of Short Bowel Syndrome Pediatric Patients (REVE)

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)

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

Study Overview

• Status: Completed
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: Teduglutide

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).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Necker - Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Revestive; Revestive® (teduglutide)is administered in children sub cutaneous injection at 0.05 mg/kg body weight once daily	Drug: Teduglutide; Daily sub cutaneous injection 0,05 mg/kg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in parenteral nutrition: Parenteral Nutrition/Resting Energy Expenditure (PN/REE)	Evaluate the efficacy of Revestive® treatment	At week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ostomy output defined as stool balance testing, urine output and plasma citrulline	Evaluate the impact of Revestive on ostomy flow	up to week 48
Change in days per week of Parenteral Nutrition (PN)	Quantify the impact of Revestive on the number of perfusion in a week	up to week 48
Change in number of stool per day	to evaluate the impact of Revestive on diarrhea	up to week 48
Change in stools consistency (Bristol stool chart)	to evaluate the impact of Revestive on diarrhea	up to week 48
Ingesta (calorimetric measure)	to evaluate the impact of Revestive on Intestinal absorption	Every 4 weeks up to week 48
Stool weight/24h	to evaluate the impact of Revestive on Intestinal absorption	Every 4 weeks up to week 48
Percentage of lipid in stool	to evaluate the impact of Revestive on Intestinal absorption	Every 4 weeks up to week 48
Percentage of nitrogen in stool	to evaluate the impact of Revestive on Intestinal absorption	Every 4 weeks up to week 48
Percentage of carbohydrate in stool	to evaluate the impact of Revestive on Intestinal absorption	Every 4 weeks up to week 48
Percentage of sodium in stool	to evaluate the impact of Revestive on Intestinal absorption	Every 4 weeks up to week 48
Number of adverse events	to evaluate the long term safety of Revestive	At week 48
Change in body weight		At baseline, then at 6 and 12 months
Change in heart rate		At baseline, then at 6 and 12 months
Change in blood pressure		At baseline, then at 6 and 12 months
Endogenous GLP-2 rates (antibody ELISA)	to evaluate the response rate of Revestive	up to week 48

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Imagine Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2018
• Primary Completion (Actual): December 11, 2019
• Study Completion (Actual): July 13, 2020

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: June 18, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): December 4, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Parenteral nutrition; Short Bowel Syndrome; Teduglutide; Intestinal failure
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Disease; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Syndrome; Short Bowel Syndrome; Physiological Effects of Drugs; Gastrointestinal Agents; Protective Agents; Radiation-Protective Agents; Teduglutide
• Other Study ID Numbers: P171002J; 2017-001405-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No