Multicenter, prospective, double-blind, randomized, three-armed, placebo-controlled study of long-term therapeutic transfer of encapsulated stool microbiome for the treatment of active ulcerative colitis

Prior treatment

• Previous operations on the colon: colectomy, partial colon resections
• No specific therapy for ulcerative colitis to date
• Previous treatment with TNF-, IL12/IL23-, IL23- or integrin-antibodies within the last 8 weeks before randomisation
• Treatment with calcineurin inhibitors within the last 4 weeks before randomization
• Treatment with JAK inhibitors (e.g., tofacitinib, filgotinib, or upadacitinib) within the last 4 weeks prior to randomization
• Treatment with S1P receptor modulators (e.g. ozanimod, etrasimod) within the last 4 weeks before randomization
• Systemic antibiotic treatment within the last 8 weeks prior to randomization.
• Previous FMT or FMFT, previous participation in this study (screening allowed)
• Use of probiotics in tablet, capsule, or powder form, or appropriate drinking yogurts (or similar) within 2 weeks prior to randomization
• Failure to ensure frozen storage of investigational products

Other illness

• Crohn's disease or indeterminate colitis or proctitis ulcerosa alone
• Acute abdomen or other clinical emergencies (e.g. toxic megacolon, fulminant gastrointestinal hemorrhage, ileus, perforation, etc.)
• current gastrointestinal infections
• severe comorbidity (e.g. insulin-dependent diabetes mellitus, decompensated liver cirrhosis, primary sclerosing cholangitis, renal impairment \> grade 2)
• Addictive or other medical conditions or circumstances that do not allow the subject to appreciate the nature, significance, scope, and possible consequences of the clinical trial

Other

• Congenital or acquired immunodeficiency
• diagnosis of a malignoma in the last 3 years
• refusal of endoscopies with video documentation
• Lack of immunity to SARS-CoV-2
• Known intolerance of metronidazole or vancomycin
• Participation in a clinical trial within the last 3 months
• Indications that the patient would be unlikely to comply with the protocol (e.g., unwillingness to cooperate - compliance questionable)

• Age between 18 and 75 years
• Prior endoscopic confirmation of UC of at least 6 months AND with a minimum disease extent of 15 cm from the anal verge.
• Having active disease, defined with a Mayo Score between 4-10 and Mayo endoscopic subscore \>1
• Failure of conventional therapy or treatment with biologicals and / or small molecules.
• previous medical therapy:
  • oral 5-ASA compounds (5-ASA); stable dosing for 4 weeks before randomization;
  • Azathioprine, 6-Mercaptopurine (6-MP) or Methotrexate (MTX); stable dosing for 8 weeks before randomization;
  • Oral corticosteroid therapy (prednisone ≤ 20 mg/day or budesonide ≤ 9 mg/day); stable dosing for 2 weeks before randomization;
  • Topical therapy (foams, clysms) with mesalazine or budesonide: stable dosing for 2 weeks before randomization.
• previous vaccination against SARS-CoV-2 or previous SARS-CoV-2 infection or positive serology
• Ability to understand and willingness to sign informed consent document in patients whom the investigator believes can and will comply with the requirements of the protocol.
• Potentially childbearing patient: negative pregnancy test and use of a highly effective contraceptive method