A clinical trial to assess the safety and effects of AGMB-129 compared to placebo in patients with fibrostenotic Crohn’s disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Agomab Spain S.L.U.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

3 Nov 2023 → ongoing

Decision date (initial)

2023-10-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Agomab Spain, S.L.U.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic

To evaluate the safety and tolerability of AGMB-129 in patients with fibrostenotic Crohn’s disease (FSCD). For Part A, compared to placebo.

Secondary objectives 2

1. To evaluate the pharmacokinetics (PK) of AGMB-129
2. To evaluate the pharmacodynamics (PD) of AGMB-129

Conditions and MedDRA coding

Fibrostenotic Crohn’s Disease

Study design 5 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 or anastomotic stricture(s), caused by CD and confirmed centrally by MRE according to the following criteria: 1. localized luminal narrowing (luminal diameter ≤50% relative to normal adjacent bowel); AND 2. bowel wall thickening (≥25% relative to adjacent bowel); AND 3. either prestenotic dilation (defined as a luminal diameter ≥3cm) or nonpassable with adult colonoscope *Note: The terminal ileum is defined as the last 15 cm of ileum proximal to the ileocecal valve or ileocolonic anastomosis. Other small bowel strictures will be considered on a case-by-case basis following discussion with the sponsor. Two strictures within 3 cm are considered the same stricture, and a long segment with multiple areas of narrowing or multiple strictures, that have inflammation between them, is counted as 1 stricture.
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. Participants should have sufficient food intake, even with diet modification, defined as a stable weight over the 4 weeks prior to screening.
4. Stable background therapy for CD and agree to maintain background therapy for the duration of Part A.
5. For Part B: Completion of the 12-week treatment period (AGMB-129 or placebo) and the Week 12 visit in the double blind treatment period (Part A) and participant is willing and able to continue treatment.
6. For Part B: Per investigator judgment, participant is able to continue or resume treatment following completion of the Week 12 visit in Part A.

Exclusion criteria 17

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, untreated colonic mucosal dysplasia, or untreated bile acid malabsorption.
2. Current or history of valvulopathy or large vessel disorder.
3. Major abnormalities documented by cardiac echocardiography with Doppler: 1. Moderate or severe heart function defect, including moderate to severe valve stenosis or regurgitation. 2. Left ventricular ejection fraction <50% of the lower limit of normal.
4. For Part B: More than 24 weeks since completion of the Week 12 visit in Part A.
5. For Part B: Experienced any AE leading to permanent treatment discontinuation during treatment with study treatment in the double-blind treatment period (Part A).
6. For Part B: Have undergone endoscopic balloon dilation or bowel surgery (resection surgery or strictureplasty) for any intestinal stricture since the Week 12 visit in Part A.
7. For Part B: Developed any condition which meets the Part A exclusion criteria.
8. For Part B: Any condition which in the opinion of the investigator affects the safety or ability to participate in Part B.
9. For Part B: Participation in any other clinical trial since the completion of the Week 12 visit in Part A.
10. Hereditary xanthinuria or molybdenum cofactor deficiency.
11. Any severe acute or chronic medical condition, psychiatric disorder, laboratory abnormality, or systemic or opportunistic infection that may increase the risk associated with study participation or study treatment administration, or may interfere with the interpretation of study results, as determined by the investigator.
12. Clinically significant vital signs, physical examination, or 12-lead ECG at screening or Baseline (PR ≥220 msec, QRS ≥120 msec and prolonged QTcF >450 msec for males or >470 msec for females), bradycardia (<50 bpm) or clinically significant ST wave changes, bundle branch block, or any other abnormal changes on the ECG that would interfere with measurement of the QT interval.
13. Receiving cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks of screening or Janus kinase inhibitor therapy within 4 weeks of screening.
14. 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.
15. CD-related complications (previous extensive small bowel resection, ileorectal anastomosis, proctocolectomy, short bowel syndrome [<200 cm remaining small bowel], ileostomy [diverting or end], colostomy, small bowel stoma, ileoanal pouch, inactive fistulae in or adjacent to an ileal stricture, anal and perianal stricture [only if not passable by scope], 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).
16. Ileitis not associated with CD (eg, ileitis associated with infections, spondyloarthropathies, ischemia, etc.).
17. Endoscopic balloon dilation or surgical treatment of the same small bowel stricture within the last 6 months prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Adverse events (AEs)
2. Clinical laboratory tests
3. Electrocardiogram (ECG) findings
4. Vital signs
5. Physical examination findings
6. 2-D echocardiogram findings

Secondary endpoints 2

1. PK parameters of AGMB-129 and its metabolites in plasma (Part A and Part B)
2. Change in gene expression at the mRNA level in ileal mucosa (Part A)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Agomab Spain S.L.U.

Sponsor organisation

Agomab Spain S.L.U.

Address

Parque Empresarial De Touro Parcelas 26-27, Fonte Diaz Fonte Diaz

City

A Coruna

Postcode

15822

Country

Spain

Scientific contact point

Organisation

Agomab Spain S.L.U.

Contact name

Clinical Operations

Public contact point

Organisation

Agomab Spain S.L.U.

Contact name

Clinical Operations

Third parties 11

Locations

6 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 76 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications