Clinical trial NCT05843578: STENOVA - A Study to Evaluate Safety, Tolerability, PK and PD of AGMB-129 in Patients With Fibrostenotic Crohn's Disease
Official title: A Phase 2a, Randomized, Placebo-controlled, Double-blind Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of AGMB-129 in Patients With Fibrostenotic Crohn's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Fibrostenotic Crohn's Disease
Lead sponsor: Agomab Therapeutics NV
Sponsor class: INDUSTRY
First posted: 2023-05-06
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled, double-blind, parallel, multicenter, phase 2a study
Primary purpose: TREATMENT

Brief summary: Many patients with Crohn's disease develop fibrotic narrowing (strictures) in their bowel, causing obstructive symptoms such as abdominal pain, cramping, or vomiting after meals. Because of these symptoms, patients often require bowel resection surgery. The objective of this clinical trial is to evaluate the safety, pharmacokinetics, and pharmacodynamics of AGMB-129 in patients with Crohn's disease and symptomatic strictures, and whether it can have a beneficial effect on intestinal strictures.

The participants will be in the Part A for a duration of up to 19 weeks including a 5 week screening period, a 12-week double-blind, placebo-controlled treatment period, and 2 week safety follow up period. Participants who continue to Part B can receive treatment for up to an additional 48 weeks, with a safety follow-up visit 2 weeks after the last dose of treatment.

Detailed description: Part A is a randomized, placebo-controlled, double-blind, parallel, multicenter, phase 2a study in participants with Crohn's disease and symptomatic intestinal strictures.

Part A consists of 3 periods (a screening period, a placebo-controlled, double-blind treatment period, and safety follow-up). After signing informed consent, eligibility will be assessed during a 5-week screening period. The presence of qualifying intestinal strictures will be assessed by ileocolonoscopy and magnetic resonance enterography (MRE). The presence of obstructive symptoms will be also evaluated.

Eligible participants will be randomized 1:1:1 to receive AGMB-129 high dose, low dose or placebo for 12 weeks.

During Screening and Week 12 visits, participants will undergo ileocolonoscopy with biopsy collection for exploring pharmacodynamics. Participants will have blood sample collection at Weeks 2, 4, 8, and 12 to assess safety, pharmacokinetics, and pharmacodynamics.

Throughout the study, participants will undergo routine safety assessments at study visits, which will include physical examination, vital signs, clinical laboratory assessment, electrocardiogram (ECG), and recording of AEs.

Part B is an open-label treatment extension for participants who have completed the double-blind treatment period in Part A.

Eligibility criteria: Inclusion Criteria (Part A):

1. Diagnosis of ileal or ileocolonic CD based on supporting guideline criteria (eg, clinical, endoscopic, and histologic evidence) established at least 3 months prior to screening.
2. Presence of at least 1 stricture in the terminal ileum within reach of an endoscope (passable or nonpassable).Strictures should be noncritical, naïve or anastomotic stricture(s), caused by CD and confirmed centrally by MRE according to the following criteria:

   * Localized luminal narrowing (luminal diameter ≤50% relative to normal adjacent bowel); AND
   * Bowel wall thickening (≥25% relative to adjacent bowel; AND
   * Either prestenotic dilation (defined as a luminal diameter ≥3 cm) or nonpassable with adult colonoscope
3. Presence of tolerable obstructive symptoms, as defined by a screening S-PRO severity score ≥2, and not expected to require hospitalization, endoscopic balloon dilation, surgical resection, or additional therapy during the study. Participant should have sufficient food intake, even with diet modification.
4. Stable background therapy for CD and agree to maintain background therapy for the study duration

Exclusion criteria (Part A):

1. History or current diagnosis of ulcerative colitis, indeterminate colitis, ischemic colitis, nonsteroidal anti-inflammatory drug-induced colitis, idiopathic colitis (ie, colitis not consistent with CD), radiation colitis, microscopic colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption.
2. CD-related complications (previous extensive small bowel resection, ileorectal anastomosis, proctocolectomy, short bowel syndrome, ileostomy \[diverting or end\], colostomy, small bowel stoma, ileoanal pouch, inactive fistulae in or adjacent to an ileal stricture, anal and perianal stricture, active intra-abdominal or perianal abscess that has not been appropriately treated, abscess in relation to the stricture, toxic megacolon, very severe inflammation, or presence of deep ulceration in the colon or terminal ileum).
3. Ileitis not associated with CD (eg, ileitis associated with infections, spondyloarthropathies, ischemia, etc.).
4. Endoscopic balloon dilation or surgical treatment of the same small bowel stricture within the last 6 months prior to screening
5. Receiving cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks of screening or Janus kinase inhibitor therapy within 4 weeks of screening.
6. Requiring continued treatment with systemically administered medications that are sensitive CYP3A4/5 substrates with a narrow therapeutic index or strong inhibitors of aldehyde oxidase or xanthine oxidase.
7. Current or history of vasculitis, valvulopathy or large vessel disorder or major abnormalities documented by cardiac echocardiography with Doppler

Inclusion Criteria (Part B):

1. Completion of the 12-week treatment period (Part A) and participant is willing and able to continue treatment.
2. Per investigator judgment, participant is able to continue or resume treatment following completion of the Week 12 visit in Part A.

Exclusion criteria (Part B):

1. More than 24 weeks since completion of the Week 12 visit in Part A.
2. Experienced any AE leading to permanent treatment discontinuation during treatment with study drug in the double blind treatment period (Part A).
3. Have undergone endoscopic balloon dilation or bowel surgery (resection surgery or strictureplasty) for any intestinal stricture since the Week 12 visit in Part A.
4. Developed any condition which meets the Part A exclusion criteria, as per investigator judgment.
5. Any condition which in the opinion of the investigator affects the safety or ability to participate in Part B.
6. Participation in any other clinical trial since the completion of the Week 12 visit in Part A.

Primary outcomes:
measure: Number of participants with adverse events (Part A and B)
timeFrame: From Screening to Week 48
measure: Number of participants with abnormal clinical laboratory values (Part A and B)
timeFrame: From Screening to Week 48
measure: Number of participants with abnormal ECG parameters (Part A and B)
timeFrame: From Screening to Week 48
measure: Number of participants with abnormal vital signs (Part A and B)
timeFrame: From Screening to Week 48
measure: Number of participants with abnormal physical exams (Part A and B)
timeFrame: From Screening to Week 48
measure: Number of participants with abnormal 2D-echocardiography (Part A and B)
timeFrame: From Screening to Week 48
Secondary outcomes:
measure: Plasma levels of AGMB-129 and its metabolites (Part A and B)
timeFrame: From Baseline to Week 48
measure: Changes in mRNA gene expression in ileal biopsies ((Part A)
timeFrame: From Baseline to Week 48
Other outcomes:
Locations:
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Digestive and Liver Center of Florida
state: Florida
city: New Albany
country: United States
facility: Gastroenterology Health Partners
state: Indiana
city: Louisville
country: United States
facility: Gastroenterology Health Partners
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana Research Center
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Cordova
country: United States
facility: Gastro One
state: Tennessee
city: Graz
country: Austria
facility: Medical University of Graz
city: Salzburg
country: Austria
facility: Gemeinnutzige Salzburger Landeskliniken Betriebsgesellschaft mbH (Landeskrankenhaus Salzburg/Regional Hospital Salzburg)
city: Vienna
country: Austria
facility: Medical University Of Vienna (AKH Wien)
city: Vienna
country: Austria
facility: Hospital Landstrasse, Department of Internal Medicine IV
city: Calgary
country: Canada
facility: University of Calgary
city: Edmonton
country: Canada
facility: Gastroenterology and Internal Medicine Research Institute (GIRI)
city: Edmonton
country: Canada
facility: South Edmonton Gastroenterology Research Clinic
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
city: North York
country: Canada
facility: TIDHI Innovation Inc.
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
city: Vancouver
country: Canada
facility: (G.I.R.I) GI Research Institute
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, Department of Hepatology and Gastroenterology
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet - University Hospital Copenhagen
city: Herlev
country: Denmark
facility: Herlev Hospital (University of Copenhagen)
city: Odense
country: Denmark
facility: Odense University Hospital
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin KöR Campus Benjamin Franklin Medizinische
city: Berlin
country: Germany
facility: Servicegesellschaft Krankenhaus Waldfriede mbH Krankenhaus Waldfriede e.V Akademisches Lehrkrankenhaus der Charite
city: Halle
country: Germany
facility: BSF Studiengesellschaft UG (Unternehmergesellschaft, haftungsbeschränkt)
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm AöR (University of Ulm)
city: Messina
country: Italy
facility: University Polyclinic Hospital "G. Martino"
city: Milan
country: Italy
facility: Humanitas Research Hospital IRCCS Istituto Clinico Humanitas
city: Milan
country: Italy
facility: Hospital San Raffaele
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria di Modena - Struttura Complessa di Gastroenterologia
city: Negrar
country: Italy
facility: Sacred Heart Don Calabria
city: Rome
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Rome
country: Italy
facility: University Polyclinic Foundation "Agostino Gemelli"
city: Białystok
country: Poland
facility: Specialist Gastrology Centre GASTROMED
city: Katowice
country: Poland
facility: Vita Longa Sp. z.o.o.
city: Lublin
country: Poland
facility: MEDRISE Sp. z o.o.
city: Poznań
country: Poland
facility: SOLUMED Medical Center
city: Sopot
country: Poland
facility: Endoskopia Sp. z o.o.
city: Tychy
country: Poland
facility: H-T. Medical Center
city: Warsaw
country: Poland
facility: WIP Warsaw IBD Point
city: Warsaw
country: Poland
facility: WSD Medi Clinical Sp. z o.o.
city: Wroclaw
country: Poland
facility: VISTAMED
city: Wrocław
country: Poland
facility: Planetmed Sp. z o.o.
city: Zamość
country: Poland
facility: ETG Zamość
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Agomab Therapeutics
name: Philippe Wiesel, MD
role: STUDY_DIRECTOR
References: