Fibrostenotic Crohn's Disease
Ontunisertib or Placebo for Adults With Fibrostenosing Crohn's Disease
This study is investigating the efficacy, safety, and dose response of three oral doses of ontunisertib compared with placebo in adults with symptomatic strictures caused by fibrostenosing Crohn's disease.
Registry title: NOV-ERA - A Clinical Trial to Assess the Efficacy and Safety of Ontunisertib Compared to Placebo in Patients With Fibrostenosing Crohn's Disease
1 recruiting U.S. site ↓Study at a glance
- Age
- 18 Years and older
- Treatment
- Ontunisertib or Placebo
- Design
- Randomized · Quadruple
- Central study contact
- Agomab Clinical Operations0032 3318 91 70clinicalstudies@agomab.com
- Sponsor
- Agomab Spain S.L.U.
Research question
Do different doses of ontunisertib, compared with placebo, affect ileal stricture passability and other measures of efficacy and safety in adults with symptomatic fibrostenosing Crohn's disease?
Participant snapshot
Who the study is looking for
- The study is looking for adults age 18 or older with ileal or ileocolonic Crohn's disease diagnosed at least 12 weeks before consent.
- Participants must have at least one ileal stricture that an endoscope cannot pass.
- The qualifying stricture may be previously untreated or located at a surgical connection and must be confirmed by centrally read magnetic resonance enterography.
- Participants must have obstructive symptoms, dietary restrictions related to the amount or type of food, altered food preparation, or a combination of these.
- Participants must be receiving stable anti-inflammatory background therapy for Crohn's disease and agree to keep it stable during the trial.
Participation overview
What participation may involve
Participation may last up to 60 weeks: a 6-week screening period, 52 weeks of assigned ontunisertib or placebo, and a 2-week follow-up period. What participation may involve: - Screening includes assessment of eligibility, obstructive symptoms, and qualifying intestinal strictures. - Participants undergo ileocolonoscopy with biopsy collection during screening and at Weeks 24 and 52. - Magnetic resonance enterography is used during screening to assess qualifying intestinal strictures, and imaging features are evaluated as study outcomes. - Blood is collected at Weeks 6, 12, 18, 24, 30, 36, 44, and 52 for safety, pharmacokinetic, and pharmacodynamic assessments. - Study visits include routine safety assessments such as physical examinations, vital signs, laboratory testing, electrocardiograms, and recording of adverse events. The registry reports up to 60 weeks of participation, including 6 weeks of screening, 52 weeks of treatment, and 2 weeks of follow-up. The registry reports two screening visits and treatment-period visits every 6 to 8 weeks; it also identifies assessments at specific treatment weeks.
Study interventions
What participants may receive or do
- Ontunisertib: Participants assigned to the high-dose group receive ontunisertib as an oral capsule for the 52-week treatment period.
- Ontunisertib: Participants assigned to the medium-dose group receive ontunisertib as an oral capsule for the 52-week treatment period.
- Ontunisertib: Participants assigned to the low-dose group receive ontunisertib as an oral capsule for the 52-week treatment period.
- Placebo: Participants assigned to the placebo group receive a matching oral capsule for the 52-week treatment period.
Study design
How the comparison works
This is a multicenter Phase 2b study with four parallel groups: high-, medium-, and low-dose ontunisertib and matching placebo. Participants are randomly assigned in equal proportions—1:1:1:1—to one of the four study groups. Participants, care providers, investigators, and outcome assessors are masked to treatment assignment. Results from the three ontunisertib dose groups are compared with results from a matching-placebo group. One of the four equally assigned groups receives a matching oral placebo capsule, corresponding to a one-in-four assignment probability.
Reported activities
Procedures and tests
- Ileocolonoscopy is performed during screening and at Weeks 24 and 52 to assess the bowel and stricture.
- Biopsy samples are collected during the screening, Week 24, and Week 52 ileocolonoscopies for pharmacodynamic exploration.
- Magnetic resonance enterography assesses the qualifying stricture and measures imaging features such as stricture length, bowel-wall thickness, and prestenotic dilation.
- Blood samples are collected to assess safety, drug and metabolite levels, and pharmacodynamic effects.
- Physical examinations and vital-sign measurements are part of routine safety monitoring.
- Clinical laboratory tests are used for safety monitoring.
- Electrocardiograms measure heart electrical activity as part of safety monitoring.
- Obstructive symptoms and symptom severity are evaluated during the study.
- Adverse events are recorded throughout the study.
- Screening may involve an echocardiogram because eligibility excludes certain heart-valve abnormalities and a left ventricular ejection fraction below 50% as locally assessed through echocardiography.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Ileal or ileocolonic Crohn's disease must have been established by clinical and endoscopic or radiological evidence at least 12 weeks before signing consent.
- At least one ileal stricture must be too narrow for an endoscope to pass.
- The stricture may be previously untreated or at a surgical connection and must be confirmed by a central review of magnetic resonance enterography.
- Participants must have obstructive or partially obstructive symptoms, relevant dietary restrictions, altered food preparation, or a combination of these.
- Anti-inflammatory background treatment for Crohn's disease must be stable, and participants must agree to keep it stable throughout the trial.
- Body mass index must be at least 18 kg/m² and below 35 kg/m².
- In the investigator's opinion, the participant must not be expected to need hospitalization, balloon dilation, bowel resection, or intensified anti-inflammatory treatment during the trial's first four weeks.
Possible reasons someone may not be able to join
- The study excludes several other current or previous colitis diagnoses, including ulcerative, indeterminate, ischemic, infectious, radiation, microscopic, and certain other forms of colitis.
- Short bowel syndrome with less than 200 cm of small bowel remaining is excluded.
- An ileostomy, colostomy, small-bowel stoma, or ileoanal pouch is excluded.
- Internal fistulas or sinus tracts arising from the narrowed area are excluded; a nonseptic perianal fistula may be allowed.
- Anal or perianal strictures are excluded.
- A suspected or active intra-abdominal or perianal abscess that has not been appropriately treated, or an abscess related to the stricture, is excluded.
- Endoscopic balloon dilation or surgery for the index small-bowel stricture within six months before screening is excluded.
- Current or previous heart-valve disease, a moderate or severe valve defect, or a left ventricular ejection fraction below 50% is excluded.
- The investigator may exclude a severe medical or psychiatric condition, laboratory abnormality, or systemic or opportunistic infection that could raise trial risk or interfere with interpreting results.
- Clinically significant abnormalities in vital signs, physical examination, or a 12-lead electrocardiogram at screening or baseline are excluded.
Important unknowns
What the record does not make clear
- The registry reports two screening visits, treatment visits every 6 to 8 weeks, and several week-specific assessments, but it does not provide a complete visit calendar or expected visit length.
- Stable anti-inflammatory Crohn's disease therapy is required, but the registry does not identify which medications or dose-stability periods are permitted.
- The registry does not report whether any current or previous medicines require a washout period.
- The registry does not describe rescue treatment or what happens if obstructive symptoms or Crohn's disease worsen.
- The registry reports ileocolonoscopies with biopsies during screening and at Weeks 24 and 52, but does not describe preparation, sedation, biopsy quantity, or procedure-related recovery.
- The registry does not state which study-related or routine-care costs are covered or billed to insurance.
- The registry does not state whether participants receive compensation or reimbursement.
- The registry does not describe transportation, lodging, or other travel support.
- The registry does not state whether any visits or assessments can be completed remotely or with a local clinician.
- The registry does not describe access to ontunisertib after the 52-week treatment period.
Before contacting the site
Questions for the study team
- Which Crohn's disease medicines and doses count as acceptable stable background therapy, and how long must they have been stable?
- What is the full visit calendar, how long are visits likely to take, and which visits require fasting, bowel preparation, or recovery time?
- What treatment or urgent-care plan applies if obstructive symptoms worsen during screening or treatment?
- What preparation, sedation, biopsy collection, and recovery should I expect for the three reported ileocolonoscopies?
- Which costs are covered, what may be billed to insurance, and are travel reimbursement or participant compensation available?
- Can any visits, blood tests, or follow-up activities be completed remotely or through a local clinician?
- What happens at the end of the 52-week treatment period, including whether continued access to ontunisertib is possible?
Before changing care
Questions for your gastroenterologist
- How stable is my Crohn's disease and stricture now, and is it medically reasonable to consider a 52-week placebo-controlled study?
- Could my current Crohn's disease treatment remain stable during the trial, and what risks would come with delaying a treatment adjustment?
- What approved treatment, endoscopic, or surgical alternatives should I compare with this study?
- How might repeated ileocolonoscopy, biopsies, magnetic resonance enterography, and blood testing affect my care or procedural risk?
- How should you and the research team coordinate monitoring and urgent care if my obstructive symptoms worsen?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
Many patients with Crohn's disease (CD) 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 efficacy, safety, and dose-response relationship of ontunisertib in participants with CD and symptomatic strictures, and contribute to the validation of novel endpoints to assess potential treatment benefit in patients with fibrostenosing Crohn's disease (FSCD). The participants will be in the trial for a duration of up to 60 weeks, consisting of a 6-week screening period (with 2 screening visits), a 52-week treatment period, and a 2-week follow-up period. The visit frequency in the treatment period will be every 6 to 8 weeks.
This is a randomized, double-blind, placebo-controlled, dose-ranging, multicenter Phase 2b trial to assess the efficacy and safety of ontunisertib in participants diagnosed with FSCD. The trial population will include adults 18 years of age and older with symptomatic FSCD based on clinical, endoscopic, and radiological criteria. This trial 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 6-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 also be evaluated. Eligible participants will be randomized 1:1:1:1 to receive AGMB-129 (Ontunisertib) high dose, medium dose, low dose or placebo for 52 weeks. During Screening and Weeks 24 and 52 visits, participants will undergo ileocolonoscopy with biopsy collection for exploring pharmacodynamics. Participants will have blood sample collection at Weeks 6, 12, 18, 24, 30, 36, 44 and 52 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 design and administration
- Organization
- Agomab Therapeutics NV
- Organization class
- Industry
- Organization study ID
- AGMB129-01-CL-201
- Lead sponsor
- Agomab Spain S.L.U.
- Sponsor class
- Industry
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Parallel
- Primary purpose
- Treatment
- Masking
- Quadruple
- Who is masked
- Participant, Care Provider, Investigator, Outcomes Assessor
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
Ontunisertib High
Ontunisertib high dose
Interventions: Drug: Ontunisertib
Experimental
Ontunisertib Medium
Ontunisertib medium dose
Interventions: Drug: Ontunisertib
Experimental
Ontunisertib Low
Ontunisertib low dose
Interventions: Drug: Ontunisertib
Experimental
Placebo
Matching placebo
Interventions: Drug: Placebo
Interventions
Drug
Ontunisertib
Oral capsule
Drug
Ontunisertib
Oral capsule
Drug
Ontunisertib
Oral capsule
Drug
Placebo
Matching oral capsule
Eligibility
18 Years and older
All
Not accepted
Inclusion criteria (7)
- Diagnosis of ileal or ileocolonic CD based on clinical and endoscopic or radiological evidence established at least 12 weeks prior to signing the ICF.Registry-derived · unreviewed
- Presence of at least 1 endoscopically non-passable ileal stricture.Registry-derived · unreviewed
- Present stricture(s) can be naïve or anastomotic, and will be confirmed by centrally read MRE.Registry-derived · unreviewed
- Presence of (sub)obstructive symptoms AND/OR dietary restrictions like limiting the amount or type of food, and/or food processing methods.Registry-derived · unreviewed
- Participants should be on stable anti-inflammatory background therapy for CD and agree to maintain stable background therapy for the duration of the trial.Registry-derived · unreviewed
- Participants should have a body mass index ≥18 kg/m2 and \<35 kg/m2.Registry-derived · unreviewed
- Not expected in the investigator's opinion to require hospitalization, endoscopic balloon dilation, surgical resection, or optimized anti-inflammatory therapy during the first 4 weeks of the trial.Registry-derived · unreviewed
Exclusion criteria (13)
- History or current diagnosis of ulcerative colitis, indeterminate colitis, ischemic colitis, nonsteroidal anti-inflammatory drug-induced colitis, idiopathic colitis (i.e., colitis not consistent with CD), radiation colitis, microscopic colitis, colonic mucosal dysplasia, untreated bile acid malabsorption, or infectious colitis.Registry-derived · unreviewed
- CD-related complications:Registry-derived · unreviewed
- Short bowel syndrome (\<200 cm small bowel remaining).Registry-derived · unreviewed
- Ileostomy (diverting or end), colostomy, small bowel stoma, or ileoanal pouch.Registry-derived · unreviewed
- Internal fistulae and sinus tracts deriving from the area of stenosis. Participants with perianal fistulae could be included if not septic.Registry-derived · unreviewed
- Anal and perianal stricture.Registry-derived · unreviewed
- Suspected or diagnosed active intra-abdominal or perianal abscess that has not been appropriately treated and abscess in relation to the stricture.Registry-derived · unreviewed
- Toxic megacolon.Registry-derived · unreviewed
- Blind-ending sinus could be included.Registry-derived · unreviewed
- Endoscopic balloon dilation or surgical treatment of the index small bowel stricture within the last 6 months prior to screening.Registry-derived · unreviewed
- Current or history of valvulopathy, or moderate or severe heart valve function defect, including moderate or severe valve stenosis or regurgitation OR left ventricular ejection fraction \<50% as assessed locally through echocardiography.Registry-derived · unreviewed
- Any other severe acute or chronic medical condition, psychiatric disorder, laboratory abnormality, or systemic or opportunistic infection that may increase the risk associated with trial participation or trial treatment administration, or may interfere with the interpretation of trial results, as determined by the investigator.Registry-derived · unreviewed
- Clinically significant abnormal vital signs, physical examination, or abnormalities at 12-lead ECG at screening or baseline.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Proportion of participants achieving endoscopic passability of the ileal index stricture
Time frame: At week 24
To evaluate the efficacy and dose-response relationship of multiple doses of ontunisertib
Secondary outcome
Proportion of participants achieving endoscopic passability of the ileal index stricture
Time frame: At week 52
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Change in reliable MRE imaging features (stricture length, bowel wall thickness, prestenotic dilatation diameter) of the index stricture
Time frame: At week 52 compared to baseline (week 1)
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Change in total SES-CD (range, 0-56 points) (Reference: https://www.giejournal.org/article/S0016-5107(04)01878-4/abstract)
Time frame: At week 52 compared to baseline
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Proportion of participants with an endoscopic response (≥50% decrease in total SES-CD) and remission (SES-CD ≤4 with no item >1)
Time frame: At week 52 compared to baseline
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Change in S-PRO severity score
Time frame: At week 52 compared to baseline
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Time to an FSCD- related event
Time frame: From baseline to week 52
To evaluate the efficacy of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Number of participants with adverse events (AEs)
Time frame: From baseline to week 52
To evaluate the safety and tolerability of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Number of participants with abnormal clinical laboratory tests
Time frame: From baseline to week 52
To evaluate the safety and tolerability of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Number of participants with abnormal ECG parameters
Time frame: From baseline to week 52
To evaluate the safety and tolerability of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Number of participants with abnormal vital signs
Time frame: From baseline to week 52
To evaluate the safety and tolerability of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Number of participants with abnormal physical examinations
Time frame: From baseline to week 52
To evaluate the safety and tolerability of ontunisertib in participants with FSCD, compared to placebo
Secondary outcome
Plasma level concentration of ontunisertib and metabolites
Time frame: From baseline to week 52
To evaluate the PK (AUC) of ontunisertib in participants with FSCD
Recruiting locations in the United States
Synergy Healthcare, LLC
RecruitingBradenton, Florida, 34209, United States
Central study contacts
Registry dates
- First posted
- Jul 6, 2026
- Primary completion
- Dec 31, 2028
- Overall completion
- Jun 30, 2029
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.