Ensayos clínicos

Inclusion Criteria:

• Male and female subjects aged 18 to 75 years, inclusive.
• IPAA for UC completed at least 1 year prior to screening.
• Active signs and symptoms of pouchitis, as follows:
  • Modified Pouchitis Disease Activity Index (mPDAI) score ≥ 5; and
  • Increased stool frequency, defined as 3 more stools per day above “normal” (after IPAA) and an absolute total of ≥ 6 stools per day.
• Chronic or recurrent pouchitis, defined by:
  • ≥ 2 episodes within 1 year prior to or including the screening period treated with antibiotic or other prescription therapy; or
  • Maintenance antibiotic therapy taken continuously for ≥ 4 weeks immediately prior to the screening endoscopy.
• Antibiotic-resistant pouchitis, defined as disease remaining active despite at least 2 weeks of antibiotic therapy.
• Histologic inflammation in the pouch, defined by a Geboes score of 3.1 or greater.
• Unlikley to conceive.
• Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and at the randomization visit prior to the first dose of study drug.
• Able to participate fully in all aspects of this clinical trial.
• Written informed consent must be obtained and fully documented.

Exclusion Criteria:

• Known Crohn’s disease (CD) or suspected CD of the pouch, defined as complex perianal/pouch fistula and/or extensive length of pre-pouch ileitis with deep ulceration.
• Diagnosed or suspected irritable pouch syndrome (IPS).
• Isolated or predominant cuffitis.
• Mechanical complications of the pouch such as stricture or fistula(e) that preclude evaluation of the pouch and terminal ileum.
• Fecal incontinence due to anal sphincter dysfunction.
• Pelvic sepsis within 12 months prior to screening.
• Planned surgery for UC, or any other elective surgery within the time frame of the study.
• Diverting stoma.
• Current bacterial or parasitic pathogenic enteric infection, including Clostridium difficile, active tuberculosis infection, known infection with hepatitis B or C virus, known infection with human immunodeficiency virus, infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 6 months prior to screening, any infection requiring antimicrobial therapy within 2 weeks prior to screening, history of more than 1 episode of herpes zoster or any episode of disseminated zoster.
• Prior biologic use restrictions and exclusions:
  • No more than 25% of enrolled subjects (in each phase) may have prior failure of any biologics;
  • Subjects who have used prior biologic therapies must have discontinued within 8 weeks of screening (or within 4 weeks if drug levels are undetectable).
• Use of any of the following prohibited therapies, except under the stated conditions (if applicable):
  • Opioids within 4 weeks prior to screening;
  • Chronic use of nonsteroidal anti-inflammatory drugs;
  • Oral 5-aminosalicylate (5-ASA), unless the dose is ≤ 4.8 g/day and has been stable for at least 4 weeks prior to screening;
  • Oral budesonide within 6 weeks of screening;
  • Other oral corticosteroids at daily doses > 20 mg prednisone or equivalent, or who started oral corticosteroids within 6 weeks prior to screening; stable doses < 20 mg prednisone or equivalent for at least 4 weeks prior to screening are permitted;
  • Any rectal compounds;
  • Immunosuppresant therapy (azathioprine, 6-mercaptopurine, methotrexate, cyclosporin) within 8 weeks prior to screening;
  • Fecal transplant within 12 weeks prior to screening;
  • Any investigational therapy within 4 weeks prior to screening.
• Diagnosed with any immune deficiency.
• History of malignancy, except for basal cell carcinoma, nonmetastatic squamous cell carcinoma of the skin, or prior malignancy with curative therapy completed at least 5 years prior to screening and no recurrence. 
• Clinically meaningful laboratory abnormalities at screening that would affect subject safety, as judged by the investigator from local testing.
• A concurrent, clinically significant, serious, unstable, or uncontrolled underlying cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitoruinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, might confound study results, pose additional risk to the subject, or interfere with the subject’s ability to participate fully in the study.
• Current or recent history of alcohol dependence or illicit drug use that, in the opinion of the investigator, may interfere with the subject’s ability to comply with the study procedures.
• Pregnant or lactating females.
• Any surgical procedure requiring general anesthesia within 1 month prior to screening, or planned elective surgery during the study.
• Mental or legal incapacitation or a history of clinically significant psychiatric disorders at the time of the screening visit that would impact the ability to participate in the trial according to the investigator.
• Concurrent participation in any other interventional study or received any investigational therapy within 1 month prior to screening.
• Previous exposure to AMT-101.
• A known hypersensitivity to AMT-101 or its excipients.