Pouchitis MedDRA version: 20.0 Level: PT Classification code 10036463 Term: Pouchitis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Sponsors
Applied Molecular Transport Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study will enroll male and female adult subjects with chronic antibiotic-resistant pouchitis. Inclusion criteria (subjects must meet the following criteria to be randomized into the study): 1. Male and female subjects aged 18 to 75 yrs, inclusive. 2. IPAA for UC completed at least 1 yr prior to screening. 3. Active signs and symptoms of pouchitis, as follows: a. Modified Pouchitis Disease Activity Index (mPDAI) score = 5, and, b. Increased stool frequency, defined as 3 more stools per day above “normal” (after IPAA) and an absolute total of = 6 stools per day. 4. Chronic or recurrent pouchitis, defined by: a. = 2 episodes within 1 year prior to or including the screening period treated with antibiotic or other prescription therapy, or, b. Maintenance antibiotic therapy taken continuously for =4 weeks immediately prior to the screening endoscopy. 5. Antibiotic-resistant pouchitis, defined as disease remaining active despite at least 2 weeks of antibiotic therapy. 6. Histologic inflammation in the pouch, defined by a Geboes score of 3.1 or greater. 7. Unlikley to conceive. 8. 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. 9. Able to participate fully in all aspects of this clinical trial. 10. Written informed consent must be obtained and fully documented. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 122 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: Exclusion criteria (subjects who meet any of the following criteria are not eligible for participation in the study): 1. 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. 2. Diagnosed or suspected irritable pouch syndrome (IPS). 3. Isolated or predominant cuffitis. 4. Mechanical complications of the pouch such as stricture or fistula(e) that preclude evaluation of the pouch and terminal ileum. 5. Fecal incontinence due to anal sphincter dysfunction. 6. Pelvic sepsis within 12 months prior to screening. 7. Planned surgery for UC, or any other elective surgery within the time frame of the study. 8. Diverting stoma. 9. Current bacterial or parasitic pathogenic enteric infection, including Clostridium difficile; 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. 10. A positive diagnostic tuberculosis (TB) test at screening (defined as a positive QuantiFERON test). 11. Prior biologic use restrictions and exclusions: a. No more than 25% of enrolled subjects (in each phase) may have prior failure of any biologics for pouchitis. b. Subjects who have used prior biologic therapies must have discontinued within 12 weeks or 5 half-lives of screening (or within 4 weeks if drug levels are undetectable). 12. Use of any of the following prohibited therapies, except under the stated conditions (if applicable): a. Opioids within 4 weeks prior to screening. b. Chronic use (>4 weeks of continuous use prior to screening) of nonsteroidal anti-inflammatory drugs, except for chronic use of low-dose 81 mg aspirin. c. 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. d. Oral budesonide within 6 weeks of screening. e. 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. f. Any rectal compounds. g. Immunosuppresant therapy (azathioprine, 6-mercaptopurine, methotrexate, cyclosporin) within 8 weeks prior to screening. h. Fecal transplant within 12 weeks prior to screening. i. Live virus vaccination within 1 month prior to screening. j. Any investigational therapy within 4 weeks prior to screening. 13. Diagnosed with any immune deficiency. 14. 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. 15. Clinically meaningful laboratory abnormalities at screening that would affect subject safety, as judged by the investigator from local testing. 16. 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 th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 2 Study Objective: - To assess the safety, tolerability, systemic exposure, and efficacy of AMT-101 in subjects with chronic antibiotic-resistant pouchitis Phase 3 Study Co-primary Objectives: - To determine the effect of AMT-101 on stool frequency in subjects with chronic antibiotic-resistant pouchitis - To determine the effect of AMT-101 on histologic disease activity in subjects with chronic antibiotic-resistant pouchitis ;Secondary Objective: Phase 2 Study Objective: - To select an AMT-101 dose for Phase 3 Phase 3 Study Objectives: - To assess the efficacy of AMT-101 on histologic, endoscopic, and other clinical signs and symptoms in subjects with chronic antibiotic-resistant pouchitis - To assess the safety and tolerability of AMT-101 in chronic antibiotic-resistant pouchitis - To assess the efficacy of AMT-101 to improve health-related quality of life (HRQOL) - To determine the systemic exposure of subjects following dosing Exploratory Objectives (both Phases): - To assess the effect of AMT-101 to reduce time to rescue therapy - To assess the pharmacodynamic (PD) effect of AMT-101 on endoscopic and histologic inflammation - To determine the mucosal tissue exposure of subjects following dosing - To assess the PD effect of AMT-101 on change in biomarkers - To assess target engagement and mechanism of action - To assess the effect of AMT-101 on work productivity ;Primary end point(s): Co-primary Efficacy Endpoints: - Proportion of subjects with a stool frequency response at Week 12; defined as a reduction of = 3 stools AND = 30% reduction in number of stools from baseline, OR back to postoperative baseline number of stools - Proportion of subjects with histologic healing at Week 12; defined as neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue (Geboes score < 3.1) ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Ranked efficacy endpoints: 1. Proportion of subjects with histologic response at Week 12; defined as a reduction in Pouchitis Disease Activity Index (PDAI) histology subscore = 2 points from baseline or a PDAI histology subscore of 0 2. Proportion of subjects with minimal histologic activity at Week 12; defined as PDAI neutrophil score = 1 and ulcer score of 0 3. Mean change in PDAI histologic subscore at Week 12 4. Proportion of subjects with 50% reduction in Simple Endoscopic Score for Crohn’s Disease (SES-CD) score at Week 12 (area within 1 cm of the pouch suture line will not be included in the endoscopic evaluation) 5. Mean change in PDAI endoscopic subscore at Week 12 6. Proportion of subjects achieving mPDAI < 5 and a reduction of overall score by = 2 points from baseline at Week 12 7. Proportion of subjects achieving PDAI < 7 and a reduction of overall score by = 3 points from baseline at Week 12 8. Proportion of subjects achieving a partial response at Week 12; defined as reduction of mPDAI score by = 2 points from baseline 9. Mean change in stool frequency at Weeks 2, 6, 8, 10, 12, and 4WPT 10. Proportion of subjects with Mayo stool frequency score of 0 or 1 at Weeks 2, 6, 8, 10, 12, and 4WPT 11. Mean change in urgency score at Week 12 and 4WPT 12. Mean change in incontinence score (St. Mark’s) at Week 12 and 4WPT 13. Mean change in rectal bleeding score at Weeks 2, 6, 8, 10, 12, and 4WPT 14. Mean change in total PDAI score at Week 12 Safety, HRQOL, and pharmacokinetic (PK) endpoints: • Proportion of subjects with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuation due to TEAEs • Assessment of laboratory parameters • Assessment of vital signs • Mean change in Inflammatory Bowel Disease Questionnaire (IBDQ), 5-dimension EuroQoL questionnaire (EQ-5D), and 36-item Short-Form questionnaire (SF-36) at Week 12 and 4WPT • Concentration of AMT-101, AMT-101 antidrug antibodies (ADAs), and total inte | — |
Countries
Belgium, Canada, France, Germany, Hungary, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial AMT-101-201
Applied Molecular Transport Inc.
Outcome results
None listed