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

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about the safety, pharmacokinetics and pharmacodynamics of AGMB-129 in patients with Crohn's disease. The main questions it aims to answer are: is AGMB-129 safe and well tolerated in these patients? what does the body do to the drug (pharmacokinetics)? what does the drug do to the body (pharmacodynamics)? 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

Detailed Description
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This is a randomized, placebo-controlled, double-blind, parallel, multicenter, phase 2a study in participants with fibrostenotic CD. 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. Magnetic resonance enterography (MRE) will be performed at screening to assess eligibility. 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, PK, and PD. 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.

Official Title
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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

Conditions
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Fibrostenotic Crohn's Disease

Intervention / Treatment
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* Drug: AGMB-129
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Presence of up to 2 ileal stricture(s) which should be noncritical naive or anastomotic stricture(s), caused by CD and with at least 1 stricture located in the (neo)terminal ileum within reach of an endoscope 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). Presence of tolerable obstructive symptoms (such as abdominal pain, abdominal pain after eating, limitations in amount or types of food, etc.), and not expected to require hospitalization, endoscopic balloon dilation, surgical resection, or additional therapy during the study. Participants should have sufficient food intake, even with diet modification. Stable background therapy for CD and agree to maintain background therapy for the study duration Exclusion criteria: 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. 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, colonic 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). Ileitis not associated with CD (eg, ileitis associated with infections, spondyloarthropathies, ischemia, etc.). Endoscopic balloon dilation or surgical treatment of the same small bowel stricture within the last 6 months prior to screening Receiving cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks of screening or Janus kinase inhibitor therapy within 4 weeks of screening. 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. Current or history of vasculitis, valvulopathy or large vessel disorder or major abnormalities documented by cardiac echocardiography with Doppler

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, placebo-controlled, double-blind, parallel, multicenter, phase 2a study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AGMB-129 High<br>AGMB-129 high dose | Drug: AGMB-129<br>* Oral capsule<br>|
| Experimental: AGMB-129 Low<br>AGMB-129 low dose | Drug: AGMB-129<br>* Oral capsule<br>|
| Experimental: Placebo<br>Matching placebo | Drug: Placebo<br>* Matching oral capsule<br>|

What is the study measuring?
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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 |