Clinical trial NCT06582264: A Phase 1b Trial to Evaluate the Safety of MB310 in Patients With Active, Mild-to-Moderate Ulcerative Colitis
Official title: A Phase 1b, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Safety, Engraftment, and Initial Signs of Clinical Activity of MB310 in Patients With Active, Mild-to-Moderate Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Ulcerative Colitis
Lead sponsor: Microbiotica Ltd
Sponsor class: INDUSTRY
First posted: 2024-09-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 1b study to evaluate the safety and tolerability of MB310 given to patients who have active mild-to-moderate ulcerative colitis.


Eligibility criteria: Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Must be aged 18 to 70 years, inclusive, at the time of signing informed consent;
* Must have newly diagnosed or a history of recurrent UC based on clinical, endoscopic, and histological assessments;
* Must have active, mild-to-moderate UC as defined by the Modified Mayo Score (MMS) of ≥4 and ≤7, and an Endoscopic Subscore of ≤2 in the most affected area proximally ≥15 cm from anal verge;
* Male patients, and female patients of childbearing potential who are at risk of pregnancy, must agree to use a highly effective method of birth control
* Female patients must not be pregnant or breastfeeding;
* Male patients must agree to abstain from sperm donation;
* Must be able to understand and comply with the Protocol requirements; and
* Must be willing and able to provide written informed consent at Screening (Visit 1).

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Disease limited to proctitis \<15 cm from anal verge;
* Short bowel or malabsorption syndromes;
* Prior intestinal or colon resection surgery (with exception of cholecystectomy or appendectomy);
* Severe/fulminant UC;
* Other forms of inflammatory bowel disease including diagnostic uncertainty by the Investigator, or functional gastrointestinal disorders;
* Positive stool test for parasites, bacterial pathogens, or Clostridium difficile;
* Use of any of the following treatments:

  * Oral 5-ASA products at a dose \>3.0 g per day (unless the use is currently stable and anticipated to remain stable during the study);
  * Aspirin or other nonsteroidal anti-inflammatory drugs (except aspirin for cardioprotective reasons at a dose of ≤325 mg per day);
  * Loperamide and other antidiarrheal agents or probiotics;
  * Antibiotics or other antibacterial treatment (unless an ophthalmic or otic antibiotic preparation, or a topical antibiotic for skin infection);
  * Faecal Matter Transplant (FMT) or administration of Vowst®, Rebiotix®, or other Live Biotherapeutic Product (LBP);
  * Intravenous or intramuscular corticosteroids;
  * Oral corticosteroids \>10 mg prednisolone or equivalent per day;
  * Any drugs formulated for rectal administration and/or interventions;
  * Immunomodulating or immunosuppressing drugs (unless the use is currently stable and anticipated to remain stable during the study);
  * Biologics, ozanimod, etrasimod, tofacitinib, filgotinib, or upadacitinib; or
  * Proton pump inhibitors (PPIs) or H2 blockers.
* Patients whose disease has not responded to or lost response to 2 or more advanced therapies (biologics or small molecules);
* Significant liver impairment;
* Concurrent primary sclerosing cholangitis;
* Clinically significant hematological function abnormalities;
* Known hypersensitivity, intolerance, or contraindication to oral vancomycin, MB310, and/or any excipients;
* History of, or known malignancy (unless adequately treated (i.e., cured) basal cell carcinoma or squamous cell carcinoma of the skin, or cervical intraepithelial neoplasia or carcinoma in situ of the cervix with no evidence of recurrence within 5 years prior to Screening);
* Any infectious disease (HIV is allowed where certain protocol-specified criteria are met);
* Significant cardiovascular condition;
* Involvement in another clinical study (unless observational) within 4 weeks of Screening from the last dose of study drug or 5 half-lives, whichever is longer; or
* Any other clinically relevant or poorly controlled, unstable condition that would confound study endpoints or adversely affect patient safety or compliance.

Primary outcomes:
measure: Incidence and causality of adverse events (AEs), treatment-emergent AES, AEs of Scientific Interest and SAEs
timeFrame: From Visit 1 to End of Follow-Up (12 weeks after the last dose of study treatment)
measure: Incidence of treatment-emergent clinically significant changes in laboratory parameters, based on haematology, clinical chemistry, and urinalysis test results
timeFrame: From Visit 1 to End of Follow-Up (12 weeks after the last dose of study treatment)
measure: Incidence of treatment-emergent clinically significant changes in 12-lead ECG parameters, vital signs, and physical examination
timeFrame: From Visit 1 to End of Follow-Up (12 weeks after the last dose of study treatment)
Secondary outcomes:
measure: Percentage of patients achieving clinical remission at Day 91
timeFrame: Day 91
measure: Percentage of patients achieving steroid-free remission at Day 91
timeFrame: Day 91
measure: Percentage of patients achieving persistent steroid-free remission at Day 91
timeFrame: Day 64 to Day 91
measure: Percentage of patients achieving clinical response at Day 91
timeFrame: Day 91
measure: Percentage of patients achieving endoscopic improvement at Day 91
timeFrame: Day 91
measure: Percentage of patients who achieve clinical improvement at Day 64 (Visit 10) and Day 91 (Visit 11)
timeFrame: Day 91
measure: Time to clinical improvement
timeFrame: End of Follow-Up (12 weeks after the last dose of study treatment)
measure: Engraftment of MB310 bacteria into patients' intestinal microbial community
timeFrame: Up to End of Follow-Up (12 weeks after the last dose of study treatment)
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Woerthersee
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic, Tokuda Hospital
city: Sofia
country: Bulgaria
facility: Diagnostic Consulting Center Convex EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Rusemed EOOD
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment
city: Varna
country: Bulgaria
facility: Diagnostic-Consulting Center
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Kermed
city: Rzeszów
country: Poland
facility: Korczowski Bartosz, Gabinet Lekarski
city: Warszawa
country: Poland
facility: Panstwowy Instytut Medyczny MSWiA - Klinika Gastroenterologi i Chorob Wewnetrznych
city: Warszawa
country: Poland
facility: Warsaw IBD Point
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny - Panstwowy Instytut Badawczy, Klinika Gastroenterologii i Chorob Wewnetrznych
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
References: