Condition médicale (spécialité visée)
Choix aire thérapeutique
Gastroentérologie
Stades de cancer
Non applicable
Biomarqueur
Non applicable
Profil des participants
Limites d'âge
Sexe(s) des participants
Femmes
Hommes
Aptitude des participants
Majeurs aptes
Critères de sélection
Critères d'inclusion
Critères d'inclusion-Maladie de Crohn :
* Diagnostic de la maladie de Crohn (CD), confirmé par endoscopie et histopathologie
* CD modérément à sévèrement actif comme défini par l'indice d'activité clinique de la maladie (CDAI) et le score endoscopique simple (SES-CD)
* Répond aux exigences de stabilisation du médicament
Critères d'inclusion-Colite ulcéreuse :
* Diagnostic de colite ulcéreuse (CU), confirmé par endoscopie et histopathologie
* CU modérément à sévèrement actif défini par un MMCS à 3 composants
* Répond aux exigences de stabilisation du médicament
Critères d'exclusion-Maladie de Crohn :
* Diagnostic de colite indéterminée
* Abscès intra-abdominal ou périnéal suspecté ou diagnostiqué lors du dépistage
* Résection antérieure de l'intestin grêle avec une longueur combinée de résection de \> 100 cm ou résection colique antérieure de \> 2 segments
* CD isolé à l'estomac, duodénum, jéjunum ou région périnéale, sans implication colique et/ou iléale
Critères d'exclusion-Colite ulcéreuse :
* Preuve actuelle ou dans l'histoire récente (dans les derniers 6 mois) de colite fulminante, mégacôlon toxique ou perforation intestinale
* Stome actuel ou besoin imminent de colostomie ou d'iléostomie
* A reçu des corticostéroïdes IV dans les 14 jours précédant le dépistage ou pendant la phase de dépistage
* Proctocolectomie totale antérieure ou colectomie subtotale
Inclusion Criteria-Crohn's Disease:
* Diagnosis of Crohn's Disease (CD), as confirmed by endoscopy and histopathology
* Moderately to severely active CD as defined by Clinical Disease Activity Index (CDAI) and Simple Endoscopic Score (SES-CD)
* Meets drug stabilization requirements
Inclusion Criteria-Ulcerative Colitis:
* Diagnosis of Ulcerative Colitis (UC), as confirmed by endoscopy and histopathology
* Moderately to severely active UC as defined by a 3-component MMCS
* Meets drug stabilization requirements
Exclusion Criteria-Crohn's Disease:
* Diagnosis of indeterminate colitis
* Suspected or diagnosed intra-abdominal or perianal abscess at Screening
* Previous small bowel resection with combined resected length of \> 100 cm or previous colonic resection of \> 2 segments
* CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or ileal involvement
Exclusion Criteria-Ulcerative Colitis:
* Current evidence or within recent history (within last 6 months) of fulminant colitis, toxic megacolon, or bowel perforation
* Current stoma or impending need for colostomy or ileostomy
* Received IV corticosteroids within 14 days prior to Screening or during the Screening Phase
* Previous total proctocolectomy or subtotal colectomy
Critères d'exclusion
General Exclusion Criteria
Sex and Reproductive Status
1. Women who are pregnant or breastfeeding.
Medical History and Concurrent Disease
2. Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis.
3. Past or current evidence of definite low-grade or high-grade colonic dysplasia that has not been completely removed.
4. Participants who are scheduled or anticipate the need for surgery, aside from dermatologic or other minor outpatient procedures.
5. Participants who have a known history of clinically significant drug or alcohol abuse, in the opinion of the Investigator.
6. Concomitant illness that, in the opinion of the Investigator, is likely to require systemic glucocorticosteroid therapy during the study (eg, moderate-to-severe asthma).
7. Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, pulmonary, cardiac, neurological, ophthalmologic, or central nervous system disease. Concomitant medical conditions that, in the opinion of the Investigator, might place the participant at unacceptable risk for participation in this study.
8. Participants with concomitant primary sclerosing cholangitis.
9. Participants with a history of cancer within the 5 years prior to Screening (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to enrollment. Participants with carcinoma in situ or localized cervical cancer who were treated with definitive surgical intervention are allowed.
10. Participants at risk for tuberculosis (TB). Specifically, participants with:
a. A history of active TB.
b. Current clinical, radiographic, or laboratory evidence of active TB.
c. Latent TB which was not successfully treated. Participants with a positive TB screening test indicative of latent TB will not be eligible for the study unless active TB infection has been ruled out, and an appropriate course of intervention for latent TB has been initiated at least 2 weeks prior to Day 1, and there is no evidence of active TB on chest X-ray during Screening. No need to test if a negative result is available within 90 days of Screening.
11. Participants with any serious bacterial infection within 3 months of Screening, unless treated and resolved with antibiotics, or any chronic bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis).
12. Any participants who are undergoing evaluation for malignancy or in whom there is a suspicion of malignancy (including breast cancer for female participants) that cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations.
13. Participants with any active infections (excluding fungal infections of nail beds) including, but not limited to, those that require IV antimicrobial treatment within 4 weeks or oral antimicrobial treatment within 2 weeks prior to dosing. Participants with evidence of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection detected during Screening are also excluded, but participants with successfully treated hepatitis C with no recurrence for ≥ 3 months are allowed. There is no need to test for hepatitis B or hepatitis C if a negative result is available within 90 days of Screening. Confirmation and documentation of a negative HIV test result within 3 months (except for participants in the Czech Republic) prior to Screening will be accepted. Participants with active documented or suspected coronavirus disease 2019 (COVID-19) infection within 4 weeks of dosing or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test within 2 weeks of dosing are excluded.
14. Participants with herpes zoster reactivation or cytomegalovirus infections that resolved less than 2 months prior to signing informed consent.
15. Participants who have received any live vaccines within 3 months of the anticipated first dose of study medication or who will have need of a live vaccine at any time during the study.
Physical and Laboratory Test Findings
16. Positive stool PCR or culture for enteric pathogens.
Note: Non-pathogenic microorganisms include, but are not limited to: Blastocystis species, Chilomastix mesnili trophozoites and/or cysts, Endolimax nana trophozoites and or cysts, Entamoeba coli trophozoites and/or cysts, Entamoeba hartmanni trophozoites and/or cysts, Iodamoeba bütschlii trophozoites and/or cysts, and Trichomonas hominis.
17. Stool positive for Clostridioides difficile (C. difficile) toxin. Participants who are positive can be retested after the completion of a full course of treatment for C. difficile infection.
18. Any of the following laboratory values:
a. Hemoglobin < 8.0 g/dL (80 g/L).
b. White blood cells < 2500/mm3 (2.5 × 109/L).
c. Neutrophils < 1000/mm3 (1 × 109/L).
d. Platelets < 100,000/mm3 (100 × 109/L).
e. Estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration formula < 40 mL/min/1.73 m2.
f. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN).
g. Any other laboratory test results that, in the opinion of the Investigator, might place the participant at unacceptable risk for participation in this study.
19. Prohibited therapies and/or medications:
a. Any marketed advanced therapy for CD or UC within 2 weeks for JAK inhibitors or S1P receptor modulators, and within 4 weeks for anti-TNF agents, anti-p19 (anti-IL-23) agents (eg, mirikizumab, risankizumab), anti-p40 (anti-IL-12/23) agents (eg, ustekinumab), or anti-integrin agents (eg, vedolizumab), prior to Day 1.
b. Any other biologic therapies with immunomodulatory potential not listed in Exclusion Criterion 19a used for CD or UC or other conditions within 8 weeks or 5 half-lives, whichever is longer, prior to Day 1.
c. Rituximab within 1 year prior to Day 1.
d. Parenteral corticosteroids within 4 weeks or rectal administration of corticosteroids within 2 weeks prior to Day 1.
e. Rectal administration of 5-ASA within 2 weeks prior to Day 1.
f. Tacrolimus, cyclosporine, mycophenolate mofetil, immunoadsorption columns (such as Prosorba columns), D-penicillamine, leflunomide, thalidomide, purified medicinal probiotics, MTX (for UC only), chronic use of non-steroidal anti-inflammatory agents (NSAIDs), and aspirin > 81 mg/day within 2 weeks prior to Day 1.
g. Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) prior to Day 1.
Other Exclusion Criteria
20. Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness.
21. Legal or mental incapacitation, or inability to understand and comply with the requirements of the study.
22. Allergy to intervention or any of the excipients.
CD Exclusion Criteria
23. Diagnosis of indeterminate colitis.
24. Suspected or diagnosed intra-abdominal or perianal abscess at Screening.
25. Known symptomatic fibrotic stricture or fibrotic stenosis not passable in endoscopy (including pediatric colonoscope).
26. Current stoma or impending need for ostomy or patients with ileo-anal pouch.
27. Previous small bowel resection with combined resected length of > 100 cm or previous colonic resection of > 2 segments.
28. Surgical bowel resection within 3 months before Screening.
30. CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or ileal involvement.
UC Exclusion Criteria
31. Current evidence or within recent history (within last 6 months) of fulminant colitis, toxic megacolon, or bowel perforation.
32. Current stoma or impending need for colostomy or ileostomy.
33. Surgical bowel resection within 3 months before Screening.
34. Received IV corticosteroids within 14 days prior to Screening or during the Screening Phase.
35. Previous total proctocolectomy or subtotal colectomy.
CD Inclusion Criteria
Exclusion criteria are outlined in the Master Protocol, plus the following ISA-specific criterion:
1. Prior exposure to MT-501 or allergy to any of the excipients.
UC Inclusion Criteria
Exclusion criteria are outlined in the Master Protocol, plus the following ISA-specific criterion:
1. Prior exposure to MT-501 or allergy to any of the excipients.