STENOVA - A Study to Evaluate Safety, Tolerability, PK and PD of AGMB-129 in Patients With Fibrostenotic Crohn's Disease

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

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 study for a total duration of up to 19 weeks, including a 5-week screening period, a 12-week double-blind, placebo-controlled treatment period where they will receive either a high or low dose or placebo (1:1:1), and 2-week safety follow-up period

Study Overview

• Status: Recruiting
• Conditions: Fibrostenotic Crohn's Disease
• Intervention / Treatment: Drug: AGMB-129; Drug: Placebo

Detailed Description

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

This study 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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tim Van Kaem; Phone Number: +3233023530; Email: clinicalstudies@agomab.com

Study Locations

• Austria
  • Graz, Austria, 8036
    • Recruiting
    • Medical University of Graz
  • Salzburg, Austria, 5020
    • Recruiting
    • Gemeinnutzige Salzburger Landeskliniken Betriebsgesellschaft mbH (Landeskrankenhaus Salzburg/Regional Hospital Salzburg)
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University Of Vienna (AKH Wien)
• Canada
  • Calgary, Canada, AB T2N 4Z6
    • Recruiting
    • University of Calgary
  • Edmonton, Canada, T5R1W2
    • Not yet recruiting
    • Gastroenterology and Internal Medicine Research Institute (GIRI)
  • Edmonton, Canada, T6K 4B2
    • Recruiting
    • South Edmonton Gastroenterology Research Clinic
  • North York, Canada, ON M6A 3B4
    • Recruiting
    • TIDHI Innovation Inc.
  • Vancouver, Canada, BC V6Z 2K5
    • Recruiting
    • (G.I.R.I) GI Research Institute
• Denmark
  • Copenhagen, Denmark, 2400
    • Recruiting
    • Bispebjerg Hospital
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev Hospital (University of Copenhagen)
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
• Germany
  • Berlin, Germany, 14163
    • Recruiting
    • Servicegesellschaft Krankenhaus Waldfriede mbH Krankenhaus Waldfriede e.V Akademisches Lehrkrankenhaus der Charite
  • Berlin, Germany, 12203/12200
    • Recruiting
    • Charite Universitatsmedizin Berlin KöR Campus Benjamin Franklin Medizinische
  • Halle, Germany, 06108
    • Recruiting
    • BSF Studiengesellschaft UG (Unternehmergesellschaft, haftungsbeschränkt)
  • Ulm, Germany, 89081
    • Recruiting
    • Universitatsklinikum Ulm AöR (University of Ulm)
• Italy
  • Milan, Italy, 20089
    • Recruiting
    • Humanitas Research Hospital IRCCS Istituto Clinico Humanitas
  • Modena, Italy, 41124
    • Recruiting
    • Azienda Ospedaliero Universitaria di Modena - Struttura Complessa di Gastroenterologia
  • Rome, Italy, 00152
    • Recruiting
    • Azienda Ospedaliera San Camillo Forlanini
• Poland
  • Katowice, Poland, 40-748
    • Recruiting
    • Vita Longa Sp. z.o.o.
  • Lublin, Poland, 20-582
    • Recruiting
    • MEDRISE Sp. z o.o.
  • Warsaw, Poland, 00-728
    • Recruiting
    • WIP Warsaw IBD Point
  • Wrocław, Poland, 52210
    • Recruiting
    • PlanetMed Sp. z o.o.
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic de Barcelona
  • Las Palmas De Gran Canaria, Spain, 35010
    • Recruiting
    • Hospital Universitario de Gran Canaria
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
• United States
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Not yet recruiting
      • Medical Research Center of Connecticut, LLC
      • Contact: PACT Gastroenterology Center; Phone Number: 203-281-5161; Email: mrcc@gastrocenter.org
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Contact: Phone Number: 305-243-8644
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Gastroenterology Clinic | Taubman Center; Phone Number: 888-229-7408
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Phone Number: 507-512-7446
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: IBD Clinical Trials Coordinator; Phone Number: 7 314-747-4236; Email: ibdstudy@wustl.edu
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Phone Number: 216-444-7000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo; Matching placebo	Drug: Placebo; Matching oral capsule
Experimental: AGMB-129 High; AGMB-129 high dose	Drug: AGMB-129; Oral capsule
Experimental: AGMB-129 Low; AGMB-129 low dose	Drug: AGMB-129; Oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	To evaluate the safety and tolerability of AGMB-129 between AGMB-129 participants and placebo participants in terms of adverse events at every visit	From Screening to Week 12
Number of participants with abnormal clinical laboratory values	To evaluate the safety and tolerability of AGMB-129 between AGMB-129 participants and placebo participants in terms of abnormal laboratory parameters at every visit	From Screening to Week 12
Number of participants with abnormal ECG parameters	To evaluate the safety and tolerability of AGMB-129 between AGMB-129 participants and placebo participants in terms of abnormal ECG parameters at every visit	From Screening to Week 12
Number of participants with abnormal vital signs	To evaluate the safety and tolerability of AGMB-129 between AGMB-129 participants and placebo participants in terms of vital signs at every visit	From Screening to Week 12
Number of participants with abnormal physical exams	To evaluate the safety and tolerability of AGMB-129 between AGMB-129 participants and placebo participants in terms of physical exams at every visit	From Screening to Week 12
Number of participants with abnormal 2D-echocardiography	To evaluate the safety and tolerability of AGMB-129 between AGMB-129 participants and placebo participants in terms of echocardiography at week 12	From Screening to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of AGMB-129 and its metabolites	To characterize the pharmacokinetics (PK) of AGMB-129 and its metabolites by measuring the amount in plasma	From Baseline to Week 12
Changes in mRNA gene expression in ileal biopsies	To characterize the pharmacodynamics of AGMB-129 by determining the gene expression in ileal biopsies	From Baseline to Week 12

Collaborators and Investigators

• Sponsor: Agomab Spain S.L.
• Investigators: Study Director: Philippe Wiesel, MD, Agomab Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: April 25, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: AGMB-129-C102

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