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
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Mage Biologics
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events
Overview
Brief Summary
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.
Detailed Description
This double-blind, placebo controlled clinical trial is intended to study the effects of oral MB-001 in patients with moderately to severely active ulcerative colitis. The primary objectives of the study are to assess safety and efficacy. Secondary and exploratory endpoints are endoscopic response, histological response, pharmacokinetics, and pharmacodynamic changes compared to baseline.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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)
Exclusion Criteria
- •The following complications:
- •Acute severe ulcerative colitis, defined by at least 6 bloody diarrhea/day AND any 1 of the following criteria: pulse \> 90 beats/min, temperature \> 37.8°C, hemoglobin \< 105 g/l, erythrocyte sedimentation rate \> 30 mm/h, or C-reactive protein \> 30 mg/l, or in the investigator's opinion, hospitalization for the treatment of UC may be imminent
- •Previous extensive colonic resection (subtotal or total colectomy)
- •Short bowel syndrome
- •Ileostomy, colostomy, ileoanal pouch, fistulae, or known fixed symptomatic stenosis of the intestine
- •Toxic megacolon or recent history (within less than 6 months) of toxic megacolon or bowel perforation
- •Diagnosis of CD or the presence or history of a fistula consistent with CD, indeterminate colitis, ischemic colitis, NSAID-induced colitis, idiopathic colitis (ie, colitis not consistent with UC), radiation colitis, microscopic colitis, infectious colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption.
- •Primary sclerosing cholangitis with uncontrolled liver function
- •Malignancies or history of malignancy within 5 years of Screening (including solid tumors and hematological malignancies), except for adequately treated or completely excised nonmetastatic basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
- •History of adenomatous polyps, unless removed.
Arms & Interventions
Matching placebo
Intervention: Matching placebo to MB-001 (Biological)
MB-001 capsules
oral capsule formulation
Intervention: MB-001 (Biological)
Outcomes
Primary Outcomes
Incidence of adverse events
Time Frame: From study start until 4 weeks after end of treatment
All adverse events and serious adverse events will be collected from the signing of the ICF until the safety follow-up visit
Changes in laboratory parameters: Platelet count
Time Frame: Week 12
Changes in laboratory parameter: Hemoglobin
Time Frame: Week 12
Changes in laboratory parameter: Hematocrit
Time Frame: Week 12
Changes in laboratory parameter: Red Blood Cell (RBC) count
Time Frame: Week 12
Changes in laboratory parameter: Prothrombin time
Time Frame: Week 12
Number of participants with abnormal laboratory tests results
Time Frame: Week 12
Blood urea nitrogen, potassium, creatinine, creatinine phosphokinase, sodium, calcium, glucose, uric acid, AST/serum glutamic-oxaloacetic transaminase, ALT/serum glutamic-pyruvic transaminase, Gamma-glutamyl transferase/transpeptidase, alkaline phosphatase, bilirubin, protein, triglycerides, cholesterol, high-density lipoprotein, low-density lipoprotein
Number of participants with abnormal urinalysis results
Time Frame: Week 12
Specific gravity, pH, colour, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase
Proportion of participants achieving clinical remission
Time Frame: Week 12
Defined by a modified Mayo Score (mMS) of not more than 2 with a Mayo endoscopic subscore (MES) not more than 1, rectal bleeding (RB) subscore of 0, and stool frequency (SF) subscore not more than 1. The mMS ranges from 0 to 9. Higher values are worse.
Secondary Outcomes
- Proportion of participants achieving endoscopic improvement(Week 12)
- Proportion of participants achieving endoscopic remission(Week 12)
- Proportion of participants achieving histologic remission(Week 12)
- Proportion of participants achieving histologic-endoscopic mucosal improvement(Week 12)
- Proportion of participants achieving mucosal healing(Week 12)