Clinical trial NCT04627025: Trial to Evaluate Efficacy and Safety of Apraglutide in SBS-IF
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Apraglutide in Adult Subjects With Short Bowel Syndrome and Intestinal Failure (SBS-IF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Short Bowel Syndrome
Keywords: Short Bowel Syndrome
Intestinal Failure
SBS
SBS-IF
GLP-2
Short Bowel Syndrome Intestinal Failure
Lead sponsor: VectivBio AG
Sponsor class: INDUSTRY
First posted: 2020-11-13
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the trial is the confirmation of the efficacy of apraglutide to evaluate the efficacy of weekly subcutaneous apraglutide in reducing parenteral support dependency.

Detailed description: This is an international, multicenter, double-blind, randomized, placebo-controlled, trial to evaluate the efficacy and safety of weekly SC injections of apraglutide in adult subjects with SBS-IF. The active pharmaceutical ingredient is apraglutide, a GLP-2 analogue.

The trial consists of a screening phase, a treatment phase of 48 weeks, and a safety follow-up phase. Trial participants will receive, after successful screening, once weekly apraglutide.

Eligibility criteria: Inclusion Criteria

1. Signed informed consent for this trial prior to any trial specific assessment.
2. Male and female subjects with SBS-IF, receiving parenteral support (PS), secondary to surgical resection of the small intestine with either stoma or colon-in-continuity (CIC).
3. Subject must require PS at least 3 days per work and be considered stable.
4. No restorative surgery intended to change PS requirements in the trial period.
5. Age ≥18 years at screening.

Exclusion Criteria:

1. Pregnancy or lactation.
2. Major abdominal surgery in the last 6 months prior to screening.
3. History of cancer (including colon carcinoma) or clinically significant lymphoproliferative disease within ≤5 years, except for adequately treated basal cell skin cancer.
4. Evidence of active inflammatory GI conditions in the previous 6 months.
5. Evidence of decompensated heart failure.
6. Evidence of severe renal or hepatic impairment.
7. Any previous use of growth factors such as growth hormone (GH), native GLP-2, GLP-1, or GLP-2 or GLP-1 analogues should be discussed with the Investigator.

Primary outcomes:
measure: Relative change from baseline in actual weekly PS volume at Week 24.
timeFrame: At week 24 of treatment
Secondary outcomes:
measure: Subjects who achieve a reduction of at least 1 day per week of PS at Weeks 24 / 48 (CIC only).
timeFrame: Weeks 24 and 48 of treatment
measure: Relative change from baseline in actual weekly PS volume at Weeks 12 / 24 / 48 (CIC only).
timeFrame: Weeks 12 / 24 / 48 of treatment
measure: Subjects reaching enteral autonomy at Weeks 24 / 48 (CIC only).
timeFrame: Weeks 24 / 48 of treatment
measure: At least 20% reduction of PS volume from baseline at Weeks 20 / 24.
timeFrame: Weeks 20 / 24 of treatment
measure: Calorie reduction in the PN at Weeks 24.
timeFrame: Weeks 24 of treatment
measure: Change from baseline on the Pittsburgh Sleep Quality Inventory (PSQI) at Weeks 24 / 48 (CIC only)
timeFrame: Weeks 24 / 48 of treatment
measure: Change from baseline on the Patient Global Impression of Change (PGIC) at Weeks 24 / 48 (CIC only)
timeFrame: Weeks 24 / 48 of treatment.
measure: Change from baseline on the Patient Global Impression of Treatment Satisfaction (PGI-TS) at week 24 and 48 (CIC only).
timeFrame: Weeks 24 / 48 of treatment
measure: Change from baseline on the Patient Global Impression of Satisfaction with Parenteral Support (PGI-SPS) at Week 24 and 48 (CIC only).
timeFrame: Weeks 24 / 48 of treatment
measure: Change from baseline on the Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Week 24 and 48 (CIC only).
timeFrame: Weeks 24 / 48 of treatment
measure: Absorption rate constant (ka) of apraglutide through population PK data analysis
timeFrame: Weeks 0 / 24 of treatment
measure: Apparent clearance (CL/F) of apraglutide through population PK data analysis
timeFrame: Weeks 0 / 24 of treatment
measure: Apparent volume of distribution (Vz/F) of apraglutide through population PK data analysis
timeFrame: Weeks 0 / 24 of treatment
measure: At least 40% reduction of PS volume at Weeks 20 and 24 (Stoma only)
timeFrame: Weeks 20 / 24 of treatment
measure: Trough plasma concentrations (Ctrough) at every other visit during the prolonged dosing period (CIC only)
timeFrame: Weeks 24 / 48 of treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Naples
country: United States
facility: Gastroenterology Group of Naples
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Novi
country: United States
facility: Henry Ford Medical Center - Columbus
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Center for Human Nutrition
state: Tennessee
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Buenos Aires
country: Argentina
facility: University Hospital Foundation Favaloro
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Gasthuisberg
state: Vlaams Brabant
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Brno
country: Czechia
facility: University Hospital Brno
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Kralove
city: Nový Jičín
country: Czechia
facility: Hospital Novy Jicin
city: Pilsen
country: Czechia
facility: University Hospital Plzen
city: Prague
country: Czechia
facility: University Hospital Kralovske Vinohrady, 2nd Internal Clinic
city: Prague
country: Czechia
facility: General University Hospital in Prague
city: Copenhagen
country: Denmark
facility: Rigshospitalet - University Hospital Copenhagen
city: Clichy
country: France
facility: Hôpital Beaujon
city: Nantes
country: France
facility: CHU Hôtel Dieu
city: Nice
country: France
facility: Hôpital ARCHET II
city: Pessac
country: France
facility: Hôpital Haut-Lévèque
city: Pierre Benite
country: France
facility: Hospices Civils de Lyon
city: Vandœuvre-lès-Nancy
country: France
facility: Brabois Adults Hospital
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Münster
country: Germany
facility: University Hospital Muenster
city: Budapest
country: Hungary
facility: Medical Centre, Hungarian Defence Forces
city: Budapest
country: Hungary
facility: Semmelweis University
city: Budapest
country: Hungary
facility: St. Imre University Teaching Hospital Budapest
city: Szeged
country: Hungary
facility: University of Szeged
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
city: Bologna
country: Italy
facility: Polyclinic S. Orsola-Malpighi
city: Rome
country: Italy
facility: University Polyclinic Foundation "Agostino Gemelli" - IRCCS
city: Torino
country: Italy
facility: Citta della salute e della Scienza di Torino Hospital
city: Kanagawa
country: Japan
facility: Yokohama Municipal Citizen's Hospital
city: Kanagawa
country: Japan
facility: Yokohama City University Medical Center
city: Miyagi
country: Japan
facility: National University Corportation Tohoku University Tohoku University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: JCHO Tokyo Yamate Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Soeul
country: Korea, Republic of
facility: Asan Medical Center
city: Soeul
country: Korea, Republic of
facility: Samsung Medical Center
city: Ålesund
country: Norway
facility: Alesund Hospital
city: Bydgoszcz
country: Poland
facility: Stadmedica, Non-Public Healthcare Facility
city: Gdansk
country: Poland
facility: COPERNICUS Limited Liability Company
city: Lublin
country: Poland
facility: Gastromed Poland Sp. z o.o.
city: Skawina
country: Poland
facility: Stanley Dudrick Multispecialty Hospital
city: Łódź
country: Poland
facility: M. Pirogow Provincial Specialized Hospital
city: Madrid
country: Spain
facility: University General Hospital Gregorio Maranon
city: Madrid
country: Spain
facility: University Hospital 12 de Octubre
city: Sevilla
country: Spain
facility: University Hospital Virgen del Rocio
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Harrow
country: United Kingdom
facility: St Mark's Hospital
city: London
country: United Kingdom
facility: Royal London Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
Study officials:
affiliation: VectivBio AG
name: Tomasz Masior
role: STUDY_DIRECTOR
References: