A Phase 1b/2a, Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of MB-001 in Participants With Moderately to Severely Active Ulcerative Colitis
The goal of this clinical trial is to learn if MB-001, an oral biologic, is able to treat patients with ulcerative colitis. Participants will be asked to take MB-001 or a matching placebo once-daily for a period of 12 weeks. Researchers will compare MB-001 to placebo to investigate its effects on clinical symptoms as well as endoscopic and histopathological findings. Patients will be offered open-label extension for another 12 weeks following the double-blind, placebo-controlled part of the study. Participants will keep a daily diary to record their symptoms and will have up to nine clinic visits.
• Nonpregnant, nonlactating adults with a diagnosis of UC extending ≥ 15 cm from the anal verge, established at least 3 months prior to Screening by clinical and endoscopic evidence of UC (colonoscopy or flexible sigmoidoscopy) and confirmed by histology.
• Moderately to severely active UC, defined as an mMS of 5 to 9, inclusive, with MES of at least 2 and RB subscore of at least 1.
• At Screening, a colonoscopy will be required if the participant has had extensive colitis or pancolitis of \> 8 years duration or left-sided colitis of \> 12 years duration but has not had a colonoscopy within 1 year of the initial Screening visit. If the participant has had a colonoscopy within 1 year of the initial Screening date, a flexible sigmoidoscopy may be used instead.
• Demonstrated, in the opinion of the investigator, an inadequate response, loss of response, or intolerance/medical contraindication to at least 1 of the following treatments at doses approved for the treatment of UC:
‣ Oral 5-ASA compounds or sulfasalazine
⁃ Oral corticosteroids (eg, prednisone, budesonide)
⁃ Immunosuppressants (eg, AZA, 6-MP, MTX)
⁃ An approved anti-integrin antibody (eg, vedolizumab)
⁃ An approved anti-IL-12/23 antibody (eg, ustekinumab)
⁃ An approved anti-IL-23 p19 antibody (eg, risankizumab, guselkumab, or mirikizumab)
⁃ An approved S1PR modulator (eg, ozanimod or etrasimod) Note: Participants who have had an inadequate response to more than 1 advanced therapy (eg, anti-integrin, anti-IL 12/23, IL-23 p19 antibody, or S1PR modulator) are not eligible (see Exclusion Criterion #15).
• Participant may be receiving a therapeutic dosage of the following drugs:
‣ Oral 5-ASA compounds or sulfasalazine, prescribed dose must be stable for at least 2 weeks before Screening endoscopy or stopped at least 2 weeks prior to Screening endoscopy
⁃ Oral corticosteroids - prednisone (max. 20 mg/day) (or equivalent) or budesonide (max. 9 mg/day) and have been at a stable dose for at least 2 weeks prior to Screening endoscopy or stopped at least 2 weeks prior to Screening endoscopy
⁃ Immunosuppressants (AZA, 6-MP, MTX) if the prescribed dose has been stable for at least 8 weeks before Screening endoscopy or stopped at least 8 weeks prior to Screening endoscopy
• POCBP:
∙ Is eligible to participate if not pregnant or breastfeeding, and the following conditions apply:
⁃ Of childbearing potential and using an acceptable contraceptive method during treatment with the IMP and for a minimum until 28 days after the last dose of IMP. The investigator should evaluate the potential or contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of IMP. AND
• Must have a negative highly sensitive pregnancy test as required by local regulations within 24 hours before the first dose of IMP,
‣ Must agree not to donate eggs (ova, oocytes) for the purpose of assisted reproduction during the study and for a period of 28 days after receiving the last dose of IMP.
• Able to participate fully in all aspects of this clinical trial. Full comprehension of consent language and informed consent must be obtained from the participant, or the participant's legally acceptable representative.