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.
Published: 09/03/2024
General Information:
The objective of the STENOVA study is to evaluate the safety, pharmacokinetics, and pharmacodynamics of the study drug AGMB-129 in patients with Crohn's disease and symptomatic strictures, and whether it can have a beneficial effect on intestinal strictures.
Eligibility:
Key Inclusion Criteria:
• Diagnosis of ileal or ileocolonic Crohn’s Disease (CD) established at least 3 months prior to screening
• Presence of at least 1 ileal stricture in the terminal ileum within reach of an endoscope and confirmed by MRE
• Presence of tolerable obstructive symptoms as assessed by a patient questionnaire
• Stable background therapy for CD and agree to maintain background therapy for the study duration
Key Exclusion Criteria
• History or current diagnosis of ulcerative colitis
• Ileitis not associated with Crohn's disease
• Endoscopic balloon dilation or surgical treatment of the same small bowel stricture within the last 6 months prior to screening
• Current or history of vasculitis
• Current or history of valvulopathy or large vessel disorder
• Major abnormalities documented by cardiac echocardiography with Doppler
• Any severe acute or chronic medical condition
• Receiving cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks of screening or Janus kinase inhibitor therapy within 4 weeks of screening
• Ongoing 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
• Clinically significant vital signs, physical examination, or 12-lead ECG at screening or Baseline, or any other abnormal changes on the screening ECG that would interfere with measurement of the QT interval
Study Details:
This is a randomized, placebo-controlled, double-blind multicenter, phase 2a study assessing the safety, pharmacokinetics (what the body does to the study drug) and pharmacodynamics (what the study drug does to the body) of 2 dose levels of AGMB-129 in participants with Crohn's disease and symptomatic 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 study treatment period, and 2-week safety follow-up period.
Participants who have completed the Week 12 visit in Part A and who have been determined eligible by the
investigator according to inclusion and exclusion criteria, may continue to Part B (Long-Term Extension). Eligible participants will receive AGMB-129 200 mg BID for up to 48 weeks.
Description of study treatment or intervention (mechanism of action):
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 study 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.
Patient Participation Requirements:
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.
At screening and Weeks 4, 8, and 12, participants will complete a 7-day diary.
In addition, participants will complete the Short Inflammatory Bowel Disease Questionnaire at screening and Weeks 4, 8, and 12.
Participants will attend a Safety Follow-up Visit 2 weeks after the last dose of study treatment for safety assessments and recording of AEs.
Possible risks and side effects:
Based upon results from preclinical and Phase I studies, the risk/benefit profile of AGMB-129 as administered in this study is considered as favorable. More detailed information can be provided by participating investigators.